The Statistical Fragility of Platelet-Rich Plasma as Treatment for Chronic Noninsertional Achilles Tendinopathy: A Systematic Review and Meta-analysis.
Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by P <.05, are often used to guide decision making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of chronic noninsertional Achilles tendinopathy (AT) by using fragility indices. The present study was a systematic review and meta-analysis of RCTs comparing outcomes after PRP injection vs alternative treatment in patients with AT. Representative data sets were generated for each reported continuous outcome event using summary statistics. Fragility indices refer to the minimal number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result into a nonsignificant result, or vice versa. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each data set until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. Of 432 studies screened, 8 studies (52 outcome events) were included in this analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, because changing only a small number of events may alter outcome significance. Level II, therapeutic study.


The relationship between calcium, MAP kinase, and DNA synthesis in the sea urchin egg at fertilization.
Fertilization releases the brake on the cell cycle and the egg completes meiosis and enters into S phase of the mitotic cell cycle. The MAP kinase pathway has been implicated in this process, but the precise role of MAP kinase in meiosis and the first mitotic cell cycle remains unknown and may differ according to species. Unlike the eggs of most animals, sea urchin eggs have completed meiosis prior to fertilization and are arrested at the pronuclear stage. Using both phosphorylation-state-specific antibodies and a MAP kinase activity assay, we observe that MAP kinase is phosphorylated and active in unfertilized sea urchin eggs and then dephosphorylated and inactivated by 15 min postinsemination. Further, Ca(2+) was both sufficient and necessary for this MAP kinase inactivation. Treatment of eggs with the Ca(2+) ionophore A23187 caused MAP kinase inactivation and triggered DNA synthesis. When the rise in intracellular Ca(2+) was inhibited by injection of a chelator, BAPTA or EGTA, the activity of MAP kinase remained high. Finally, inhibition of the MAP kinase signaling pathway by the specific MEK inhibitor PD98059 triggered DNA synthesis in unfertilized eggs. Thus, whenever MAP kinase activity is retained, DNA synthesis is inhibited while inactivation of MAP kinase correlates with initiation of DNA synthesis.


Circularly polarised luminescence laser scanning confocal microscopy to study live cell chiral molecular interactions.
The molecular machinery of life is founded on chiral building blocks, but no experimental technique is currently available to distinguish or monitor chiral systems in live cell bio-imaging studies. Luminescent chiral molecules encode a unique optical fingerprint within emitted circularly polarized light (CPL) carrying information about the molecular environment, conformation, and binding state. Here, we present a CPL Laser Scanning Confocal Microscope (CPL-LSCM) capable of simultaneous chiroptical contrast based live-cell imaging of endogenous and engineered CPL-active cellular probes. Further, we demonstrate that CPL-active probes can be activated using two-photon excitation, with complete CPL spectrum recovery. The combination of these two milestone results empowers the multidisciplinary imaging community, allowing the study of chiral interactions on a sub-cellular level in a new (chiral) light.


Highly Efficient Hydroisomerization of Endo-Tetrahydrodicyclopentadiene to Exo-Tetrahydrodicyclopentadiene over Pt/HY.
The fast deactivation caused by serious formation of coke is a major challenge in catalytic isomerization of endo-tetrahydrodicyclopentadiene (endo-THDCPD) into exo-tetrahydrodicyclopentadiene (exo-THDCPD) over the HY zeolite. In order to suppress the coke formation for the isomerization process, the conventional HY zeolite was modified with Pt at 0.3 wt %. Then, the hydroisomerization of endo-THDCPD into exo-THDCPD was evaluated over a fixed-bed reactor. The catalytic stability of Pt/HY was greatly enhanced in comparison to that of the HY zeolite. The Pt/HY catalyst provided 97% endo-THDCPD conversion and 96% selectivity for exo-THDCPD without deactivation after 100 h. Moreover, the formation mechanism of coke on the HY zeolite during the isomerization process was proposed based on the results of the coke analysis. It was indicated that the coke was generated from the oligomerization and condensation of olefin species, which originated from the β-scission reaction or hydride transfer reaction of intermediates. The lower coke formation over Pt/HY was attributed to the lower amount of coke precursors, which could be hydrogenated by activated H2 over Pt sites. Therefore, Pt on Pt/HY and H2 were two crucial factors in efficiently enhancing the catalytic stability of the HY zeolite for this isomerization reaction.


Salt-Induced Metabolic Changes in Dunaliella salina.
An increase of medium NaCl concentration induces Dunaliella cells to evolve O(2) photosynthetically even in the absence of CO(2). This NaCl-induced O(2) evolution may reflect the induced conversion of reserve carbohydrate to glycerol. The quantum yield for the NaCl-induced O(2) evolution, in the absence of CO(2), is 1.5-fold higher than that obtained for CO(2) fixation. Since the synthesis of glycerol from reserve carbohydrate in the absence of CO(2) requires only 0.5 ATP/NADPH, whereas photosynthesis requires at least 1.3 ATP/NADPH, it is concluded that the ATP/2e(-) ratio coupled to NADP reduction in Dunaliella is lower than required for CO(2) fixation.


Diagnosing schistosomiasis by detection of cell-free parasite DNA in human plasma.
Schistosomiasis (bilharzia), one of the most relevant parasitoses of humans, is confirmed by microscopic detection of eggs in stool, urine, or organ biopsies. The sensitivity of these procedures is variable due to fluctuation of egg shedding. Serological tests on the other hand do not distinguish between active and past disease. In patients with acute disease (Katayama syndrome), both serology and direct detection may produce false negative results. To overcome these obstacles, we developed a novel diagnostic strategy, following the rationale that Schistosoma DNA may be liberated as a result of parasite turnover and reach the blood. Cell-free parasite DNA (CFPD) was detected in plasma by PCR. Real-time PCR with internal control was developed and optimized for detection of CFPD in human plasma. Distribution was studied in a mouse model for Schistosoma replication and elimination, as well as in human patients seen before and after treatment. CFPD was detectable in mouse plasma, and its concentration correlated with the course of anti-Schistosoma treatment. Humans with chronic disease and eggs in stool or urine (n = 14) showed a 100% rate of CFPD detection. CFPD was also detected in all (n = 8) patients with Katayama syndrome. Patients in whom no viable eggs could be detected and who had been treated for schistomiasis in the past (n = 30) showed lower detection rates (33.3%) and significantly lower CFPD concentrations. The duration from treatment to total elimination of CFPD from plasma was projected to exceed one year. PCR for detection of CFPD in human plasma may provide a new laboratory tool for diagnosing schistosomiasis in all phases of clinical disease, including the capacity to rule out Katayama syndrome and active disease. Further studies are needed to confirm the clinical usefulness of CFPD quantification in therapy monitoring.


Direct and highly stereoselective synthesis of quinolizidine iminosugars promoted by l-proline-Et3N.
A mild and effective method for the synthesis of polyhydroxylated quinolizidine iminosugars is described. The Mannich-type reaction of iminosugar C-glycosides with aldehyde in the presence of l-proline-Et3N provides polyhydroxylated quinolizidine iminosugars, and desired products as the potential glucosidase inhibitors were obtained in good to excellent yields with excellent stereoselectivity.


Biogenesis of the hydrogenosome in the anaerobic protist Trichomonas vaginalis.
Trichomonas vaginalis is a primitive protist that lacks mitochondria and peroxisomes. This aerotolerant anaerobe does, however, contain a specialized organelle involved in carbohydrate metabolism called the hydrogenosome. Hydrogenosomes are the site of fermentative oxidation of pyruvate, coupled to ATP production via substrate level phosphorylation. The organelle is surrounded by 2 membranes and appears to contain no genetic material. Hydrogenosomes are proposed to have arisen either through the conversion of mitochondria or via endosymbiosis with an anaerobic bacterium. Our studies show that hydrogenosomal proteins are synthesized on free polyribosomes and are, thus, posttranslationally translocated into the organelle. The 2 hydrogenosomal proteins we have examined in detail, ferredoxin and the beta subunit of succinyl CoA synthetase, appear to be synthesized as larger precursors that contain an 8- or 9-amino acid amino-terminal extension, respectively. These apparent leader sequences are absent from the mature proteins found in hydrogenosomes. The biochemical properties of the amino-terminal extensions are similar to one another and to mitochondrial presequences. These observations are consistent with the hypotheses that the specificity of protein translocation into hydrogenosomes is conferred by a short amino-terminal signal sequence and that the mechanisms underlying translocation are similar to that of mitochondria. Using in vitro import assays, we have shown that this short leader sequence is absolutely required for association of hydrogenosomal proteins with the organelle and that this association is dependent on ATP, temperature, and the presence of intact organelles.


Isolation of osteocytes from mature and aged murine bone.
Osteocytes are thought to be the mechanosensors of bone by sensing mechanical loads imposed upon the bone and transmitting these signals to the other bone cells to initiate bone modeling and remodeling. The location of osteocytes deep within bone is ideal for their function. However, this location makes the study of osteocytes in vivo technically difficult. There are several methods for obtaining and culturing primary osteocytes for in vitro experiments and ex vivo observation. In this chapter, several proven methods are discussed including the isolation of avian osteocytes from chicks and osteocytes from calvaria and long bones of young mice. A detailed protocol for the isolation of osteocytes from hypermineralized bone of mature and aged animals is provided.


Comparative Analysis of Ultrasound Guided Central Venous Catheterization Compared to Blind Catheterization.
Central venous catheterization is performed by the landmark method and ultrasound guided method. The purpose of the study was to compare the success, average number of attempts, average time to return of blood, and complication rate between the two methods. This was a prospective study done in the Intensive Care Unit of the Acibadem Sistina Clinical Hospital, in Skopje. There were 400 patients in need of central venous catheter and they were prospectively randomized in two groups. The patients randomized in the examined-ultrasound group underwent real-time ultrasound-guided catheterization and the patients randomized in the control-landmark group were catheterized using the landmark method. Internal Jugular, Subclavian and Femoral vein were catheterized in both groups. The Overall success, success on the first attempt, time to the return of blood, number of attempts and complications at the moment of catheterization such as arterial puncture, pneumothorax and hematoma formation were the main outcome measures. The catheterization using the landmark method was successful in 90.5% of patients, 60.5% of which during the first attempt. The cannulation using real-time ultrasound guidance was successful in 98% of patients with a first pass success of 77%. The complication rate with the landmark method was 14.5% versus 4% with real-time ultrasound guidance p<0.05(p=0.0008). Real-time ultrasound guidance improves success, decreases number of attempts, decreases average time to the return of blood and reduces mechanical complications rate.


[From pharmacogenetics to pharmacogenomics: the start of a new era of personalized medicine in nephrology].
Recent evidence suggests that adverse drug reactions are a major cause of death and hospital admissions in Europe and the United States. Environmental/ non-genetic as well as genetic factors are responsible for the great interpatient variability in drug metabolism and in the molecular interactions between drugs and therapeutic targets. By means of pharmacogenetic approaches, several genetic settings have been linked to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, which analyze single genes or candidate pathways, cannot be considered ideal because the overall pharmacological effects of drugs typically are not dependent on monogenic traits. Therefore, to identify the multigenetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole-genome, high-throughput technologies. In nephrology, only few pharmacogenomics reports have been published to date, suggesting the need to enlarge the number of projects and increase the research budget for this important research field. In the future, we would expect that by applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic makeup, to carefully monitor the efficacy and toxicity of a given drug, and to modify the dose and number of medications to obtain predefined clinical outcomes.


Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes.
To investigate the effects of rapamycin on glutamate uptake in cultured rat astrocytes expressing N-terminal 552 residues of mutant huntingtin (Htt-552). Primary astrocyte cultures were prepared from the cortex of postnatal rat pups. An astrocytes model of Huntington's disease was established using the astrocytes infected with adenovirus carrying coden gene of N-terminal 552 residues of Huntingtin. The protein levels of glutamate transporters GLT-1 and GLAST, the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the autophagy substrate p62 in the astrocytes were examined using Western blotting. The mRNA expression levels of GLT-1 and GLAST in the astrocytes were determined using Real-time PCR. [(3)H]glutamate uptake by the astrocytes was measured with liquid scintillation counting. The expression of mutant Htt-552 in the astrocytes significantly decreased both the mRNA and protein levels of GLT-1 but not those of GLAST. Furthermore, Htt-552 significantly reduced [(3)H]glutamate uptake by the astrocytes. Treatment with the autophagy inhibitor 3-MA (10 mmol/L) significantly increased the accumulation of mutant Htt-552, and reduced the expression of GLT-1 and [(3)H]glutamate uptake in the astrocytes. Treatment with the autophagy stimulator rapamycin (0.2 mg/mL) significantly reduced the accumulation of mutant Htt-552, and reversed the changes in GLT-1 expression and [(3)H]glutamate uptake in the astrocytes. Rapamcin, an autophagy stimulator, can prevent the suppression of GLT-1 expression and glutamate uptake by mutant Htt-552 in cultured astrocytes.


Setting Limits: Gambling, Science and Public Policy-summary of results.
The gambling industry has grown into a global business in the 21st century. This has created the need for a new emphasis on problem prevention. This article highlights the core themes of the book Setting Limits: Gambling, Science and Public Policy, taking a broad view of the consequences of gambling for society as a burden on health, well-being and equality. The book covers the extent of gambling and gambling-related problems in different societies and presents a critical review of research on industry practices, policy objectives and preventive approaches, including services to people suffering from gambling and its consequences. It discusses the developments in game characteristics and gambling environments and provides evidence on how regulation can affect those. Effective measures to minimize gambling harm exist and many are well supported by scientific evidence. They include restrictions on general availability as well as selective measures to prevent gamblers from overspending. The revenue generated from gambling for the industry, governments, and providers of public services funded from gambling returns presents an obstacle to developing policies to implement harm-reduction measures. A public interest approach must weigh these interests against the suffering and losses of the victims of gambling.


Visible Light Generation of a Microsecond Long-Lived Potent Reducing Agent.
Photoexcitation of molecular radicals can produce strong reducing agents; however, the limited lifetimes of the doublet excited states preclude many applications. Herein, we propose and demonstrate a general strategy to translate a highly energetic electron from a doublet excited state to a ZrO2 insulator, thereby increasing the lifetime by about 6 orders of magnitude while maintaining a reducing potential less than -2.4 V vs SCE. Specifically, red light excitation of a salicylic acid modified perylene diimide radical anion PDI•- anchored to a ZrO2 insulator yields a ZrO2(e-)|PDI charge separated state with an ∼10 μs lifetime in 23% yield. The ZrO2(e-)s were shown to drive CO2 → CO reduction with a Re catalyst present in micromolar concentrations. More broadly, this strategy provides new opportunities to reduce important reagents and catalysts at low concentrations through diffusional electron transfer.


Contact lens fitting after photorefractive keratectomy.
This study evaluated contact lens fitting and the longer term response of the photorefractive keratectomy (PRK) cornea to lens wear. In PRK for myopia problems such as regression, anterior stromal haze, irregular astigmatism, halo aberration, and anisometropia have been reported. Certain patients therefore require contact lens correction to obtain best corrected visual acuity (BCVA). From an original cohort of 80 patients, 15 were dissatisfied with their visual outcome 6 months after PRK. Ten of these were fitted with lenses and monitored regularly. The best fit rigid gas permeable lens of diameter 9.20-10.00 mm was generally 0.10 mm steeper than mean keratometry readings. Because of lid discomfort five patients were refitted with daily wear soft lenses. All 10 achieved satisfactory lens wear of 10 hours per day. Central corneal steepening of 0.75 D (0.15 mm) occurred in one patient. Two patients had slight central corneal flattening. Three patients discontinued lens wear as they found lens care a nuisance. Four finally opted for retreatment by PRK. In most cases, contact lenses gave good visual acuity and, in cases of mild irregular astigmatism, a significant improvement over spectacle BCVA. No significant adverse reaction to contact lens wear was found. Although ocular tolerance of lenses was satisfactory, several patients discontinued lens wear or sought improved unaided vision.


An Extracellular Protein from Phytophthora parasitica var nicotianae Is Associated with Stress Metabolite Accumulation in Tobacco Callus.
The most abundant extracellular protein produced by Phytophthora parasitica var nicotianae at early stages of rapid growth in culture has a molecular weight of 46 kilodaltons and has been designated Ppn 46e. Culture conditions for the production of this protein have been optimized and the protein has been purified by gel filtration and ion-exchange chromatography. Ppn 46e is a soluble, acidic protein (pI 4.67). The amino acids Asx (aspartic acid or asparagine), alanine, glycine, Glx (glutamic acid or glutamine), and serine are the most abundant at 13.4%, 12.3%, 12.1%, 9.3%, and 9.3% of the residues, respectively. The purified protein is, by weight, 1.8% glucose, 1.6% mannose, and 0.5% galactose. A bioassay for Ppn 46e based on tobacco callus has been developed. In this assay as little as 20 nanograms (4.3 x 10(-13) mole) Ppn 46e causes the accumulation of the sesquiterpenoid phytoalexin, capsidiol, as estimated by gas chromatography. Levels of capsidiol of 25 micrograms per gram fresh weight were elicited by 80 nanograms Ppn 46e per callus piece. Pretreatment of the protein with either pronase or by boiling resulted in a loss of elicitor activity. Periodate treatment, which inactivates glucan elicitors, did not affect the ability of Ppn 46e to cause capsidiol accumulation. Monospecific antibodies to Ppn 46e were raised in mice. Western blotting experiments employing these antibodies showed that Ppn 46e was present in infected tobacco plants. Dot blotting experiments revealed the presence of the Ppn 46e epitope(s) in Phytophthora megasperma, P. cactorum, P. cinnamomi, and P. infestans but not in Fusarium.


Air kerma standard for calibration of well-type chambers in Brazil using 192Ir HDR sources and its traceability.
In Brazil there are over 100 high dose rate (HDR) brachytherapy facilities using well-type chambers for the determination of the air kerma rate of 192Ir sources. This paper presents the methodology developed and extensively tested by the Laboratorio de Ciencias Radiologicas (LCR) and presently in use to calibrate those types of chambers. The system was initially used to calibrate six well-type chambers of brachytherapy services, and the maximum deviation of only 1.0% was observed between the calibration coefficients obtained and the ones in the calibration certificate provided by the UWADCL. In addition to its traceability to the Brazilian National Standards, the whole system was taken to the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) for a direct comparison and the same formalism to calculate the air kerma was used. The comparison results between the two laboratories show an agreement of 0.9% for the calibration coefficients. Three Brazilian well-type chambers were calibrated at the UWADCL, and by LCR, in Brazil, using the developed system and a clinical HDR machine. The results of the calibration of three well chambers have shown an agreement better than 1.0%. Uncertainty analyses involving the measurements made both at the UWADCL and LCR laboratories are discussed.


Supramolecular Ionic-Liquid Gels with High Ionic Conductivity.
Supramolecular ionogels were prepared by the gelation of room-temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4 ]) with (S,S)-bis(leucinol)oxalamide. Remarkably, the ionic conductivity of solutions and ionogels with low gelator concentrations is higher than that of neat [BMIm][BF4 ]. On the basis of molecular dynamics simulations and quantum mechanical calculations, the origin of this phenomenon is attributed to the higher affinity of gelator molecules towards [BF4 ](-) ions, which reduces the electrostatic attraction between [BMIm](+) and [BF4 ](-) and thus increases their mobility. With increasing gelator concentration, the ionic conductivity decreases due to the formation of a denser gelator matrix, which hinders the pathways for ionic transport. However, even for very dense ionogels, this decrease is less than one order of magnitude relative to neat [BMIm][BF4 ], and thus they can be classified as highly conductive materials with strong potential for application as functional electrolytes.


Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial.
Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17beta-estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women. Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), meeting criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17beta-estradiol (100 microgram) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Asberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores. Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17beta-estradiol compared with 5 (20%) in the placebo group (P =.001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups. Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women.


Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein.
In the present study, we demonstrate the presence of Ca(2+)-activated K+ channels in rat glomerulosa cells. We find that angiotensin II (Ang II) inhibits this charybdotoxin-sensitive current. The effect of Ang II was dose-dependent with an inhibition constant (Ki) of 0.98 nM and a maximal effect observed at 200 nM. Time course of the blockage was as rapid as the one induced by charybdotoxin. This effect is mediated by the AT1 receptor subtype of Ang II, since it is blocked by DUP 753 but is unaffected by CGP 42112. Activation of protein kinase C by phorbol dibutyrate (1 microM) or dialysis of the cell with inositol 1,4,5-triphosphate (20 microM) were ineffective in blocking the current. However, experiments done with GDP beta S and GTP gamma S indicated that a G protein was involved. The inhibitory effect of Ang II was not pertussis toxin-sensitive, which excludes Gi protein, but was abrogated if an antibody raised against the alpha-subunit of the Gq/11 protein was present in the patch pipette medium. Further analysis showed that the Ca(2+)-activated K+ channel was able to modulate the membrane potential according to the level of intracellular calcium concentration ([Ca2+]i). Whereas a thapsigargin-induced increase in [Ca2+]i hyperpolarized the membrane, this effect was not observed when Ang II was used to increase [Ca2+]i because of the blockage of the Ca(2+)-activated K+ current. The blockage of Ca(2+)-activated K+ current by Ang II would result in a synergistic effect on the Ang II-induced depolarization, thus favoring Ca2+ influx, an event essential to secretion.


Lens epithelium-derived growth factor: effects on growth and survival of lens epithelial cells, keratinocytes, and fibroblasts.
We isolated a clone encoding a protein from a human lens epithelial cell (LEC) cDNA library with antibody (Ab) from a cataract patient and named it "lens epithelium-derived growth factor" (LEDGF). LEDGF is found to be identical to p75, a coactivator of both transcription (1) and pre-mRNA splicing (2). In serum-free medium LEDGF stimulated growth of LECs, cos7 cells, skin fibroblasts, and keratinocytes, and prolonged cell survival. Without LEDGF, the aforementioned cells did not survive. Also in serum-free medium, Ab to LEDGF neutralizing LEDGF blocked cell growth and caused cell death. Thus, LEDGF, a regulatory factor, may play an important role for growth and survival of a wide range of cell types.


[Peritoneoscopy and liver biopsy in the diagnosis of liver disease (author's transl)].
In two prospective studies including 962 patients and one retrospective study including 165 patients the problem was investigated, to what extend ultrasonography might change the diagnostic value of clinical examination, peritoneoscopy, guided liver biopsy and blind liver biopsy. It turned out, that liver biopsy is the method of choice in diffuse-parenchymatous disease (e.g. chronic active hepatitis, chronic persistent hepatitis, fatty liver), whereas laparoscopy is to be preferred if focal lesions (e.g. liver carcinoma) are present. Diffuse liver disease was present in 80% of the cases investigated; in this group of patients the diagnostic value of blind biopsy is equivalent to the diagnostic value of guided biopsy. Thus, blind biopsy does yield satisfactory results in most patients if it is possible to differentiate between diffuse and focal disease by ultrasonography. Such differentiation could be achieved in 77-98% of our cases, thus ultrasonography could intake a decrease in numbers of peritoneoscopies and an increase of blind liver biopsy.


Transcriptome analyses of the Dof-like gene family in grapevine reveal its involvement in berry, flower and seed development.
The Dof (DNA-binding with one finger) protein family spans a group of plant transcription factors involved in the regulation of several functions, such as plant responses to stress, hormones and light, phytochrome signaling and seed germination. Here we describe the Dof-like gene family in grapevine (Vitis vinifera L.), which consists of 25 genes coding for Dof. An extensive in silico characterization of the VviDofL gene family was performed. Additionally, the expression of the entire gene family was assessed in 54 grapevine tissues and organs using an integrated approach with microarray (cv Corvina) and real-time PCR (cv Pinot Noir) analyses. The phylogenetic analysis comparing grapevine sequences with those of Arabidopsis, tomato, poplar and already described Dof genes in other species allowed us to identify several duplicated genes. The diversification of grapevine DofL genes during evolution likely resulted in a broader range of biological roles. Furthermore, distinct expression patterns were identified between samples analyzed, corroborating such hypothesis. Our expression results indicate that several VviDofL genes perform their functional roles mainly during flower, berry and seed development, highlighting their importance for grapevine growth and production. The identification of similar expression profiles between both approaches strongly suggests that these genes have important regulatory roles that are evolutionally conserved between grapevine cvs Corvina and Pinot Noir.


Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate.
Solid tumors have a heterogeneous pathophysiology, which has a major impact on therapy. Using SW1222 colorectal xenografts grown in nude mice, we have shown that antibody-targeted radioimmunotherapy (RIT) effectively treated the well-perfused tumor rim, producing regressions for approximately 35 days, but was less effective at the more hypoxic center. By 72 h after RIT, the number of apoptotic cells rose from an overall value of 1% in untreated tumors to 35% at the tumor periphery and 10% at the center. The antivascular agent disodium combretastatin A-4 3-O-phosphate (CA4-P) rapidly reduced tumor blood flow to 62% of control values by 1 h, 23% by 3 h, and between 32-36% from 6 to 24 h after administration. This created central hemorrhagic necrosis, but a peripheral rim of cells continued to grow, and survival was unaffected. Changes in the pattern of perfusion across the tumor over time were zonal. Untreated mice showed perfusion throughout the tumor, with greatest activity at the rim. There was an overall reduction at 1 h, and total cessation of central perfusion from 3 h onward. A narrow peripheral rim of perfusion was always present, which increased in intensity and extent between 6 and 24 h, either through reperfusion or new vessel growth. Combining these two complementary therapies (7.4 MBq (131)I-labeled anti-carcinoembryonic antigen IgG i.v. plus a single 200 mg/kg dose of CA4-P i.p.) produced complete cures in five of six mice for >9 months. Allowing maximal tumor localization of antibody (48 h) before blood flow inhibition by CA4-P increased tumor retention by two to three times control levels by 96 h without altering normal tissue levels, as confirmed by gamma counting and phosphor image analysis. The success of this combined, synergistic therapy was probably the result of several factors: (a) the killing of tumor cells in the outer, radiosensitive region by targeted radiotherapy; (b) enhancement of RIT by entrapment of additional radioantibody after combretastatin-induced vessel collapse; and (c) destruction of the central, more hypoxic and radioresistant region by CA4-P. This work demonstrates the need to consider cancer treatment in a biologically heterogeneous setting, if results are to be effectively translated to the clinic.


Diagnosis and clinical findings of Kienböck's disease.
The clinical presentation and history of patients with Kienböck's disease do not permit differentiating avascular necrosis of the lunate from vague wrist pathology of a variety of causes. Diagnosis and evaluation of this disorder therefore require appropriate imaging studies. Plain-film radiography, tomography, and bone scintigraphy are useful screening tests, but MRI yields a definitive diagnosis. CT is also valuable for delineating structural changes and the amount of collapse in the lunate. The staging of Kienböck's disease is based on clinical and radiographic data.


Living with asthma: the experiences of young people at home and at school.
This study is concerned with how young people with moderate to severe asthma live with and explain the disorder and manage the resulting symptoms. Based on in-depth interviews with 55 young people aged 11-16 living in West London, it shows that asthma restricted their lives at school and recreationally but that they were actively involved with their condition and its management. The study reveals that while prescribed medicines in the form of inhalers were used as the primary means of coping with asthma episodes, the young people were concerned about being dependent on such medicines, in line with more general ambivalence in late modern cultures about the long term use of prescribed medicines. It also demonstrates how social relations in particular contexts help to determine the extent to which asthma episodes can be managed.


Effects of Dietary Zn/Se and α-Tocopherol Supplementation on Metabolic Milieu, Haemogram and Semen Traits of Breeding Stallions.
Trace element status and metabolic milieu are sometimes overlooked in common veterinary clinical practice across animal species. The evaluation of requirements of trace elements, in fact, may be useful to prevent the perturbation of tissue-specific metabolic impair. In particular, essential trace elements in the diet play key roles within sub-cellular metabolic patterns with macro effects at the systemic level, like blood cell stability and semen quality. This effect was studied in breeding stallions, in which semen quality and haemogram are important for reproduction. A case-control feeding trial involved 40 stallions (age: 8-21 years; body weight, BW: 510-531 kg) of one stud centre, allotted to two experimental groups (n = 20 control, CON vs. n = 20 supplemented, SUPPL100), following a matched-pairs approach based on age. Supplemented stallions (SUPPL100) received a mixed mineral and vitamin supplement of Zn/Se and α-tocopherol (α-TOH) (100 g/day stallion) to compound feed, fed as control diet to horses of the control group (CON). Horses resulted deficient in circulating α-TOH and Zn at the start, though clinically healthy. After supplementation, different plasmatic levels of α-TOH, Zn and Se were found between groups. Circulating basophils (BASO) and mean cell haemoglobin concentration (MCHC) were affected by the dietary treatment (p < 0.05). Plasmatic Se affected monocyte count, haematocrit, mean cell volume and mean cell haemoglobin concentration. Semen traits were not affected by the dietary treatment per se, except for mobile/progressive sperm cells (%) of stallions aged > 13 years marginal circulating levels of α-TOH (p = 0.04). Ameliorating the micromineral status showed to improve the haemogram of stallions in view of circulating levels of Cu. Semen quality appeared to be strongly dependent on animal effects.


Online Condition Monitoring of a Rail Fastening System on High-Speed Railways Based on Wavelet Packet Analysis.
The rail fastening system is an important part of a high-speed railway track. It is always critical to the operational safety and comfort of railway vehicles. Therefore, the condition detection of the rail fastening system, looseness or absence, is an important task in railway maintenance. However, the vision-based method cannot identify the severity of rail fastener looseness. In this paper, the condition of rail fastening system is monitored based on an automatic and remote-sensing measurement system. Meanwhile, wavelet packet analysis is used to analyze the acceleration signals, based on which two damage indices are developed to locate the damage position and evaluate the severity of rail fasteners looseness, respectively. To verify the effectiveness of the proposed method, an experiment is performed on a high-speed railway experimental platform. The experimental results show that the proposed method is effective to assess the condition of the rail fastening system. The monitoring system significantly reduces the inspection time and increases the efficiency of maintenance management.


Standard transport channels of X-ray beamlines at SPring-8.
SPring-8 is constructing most of its beamlines using a combination of standardized components. The structures of the beamlines are also standardized according to the light-source characteristics. Specifications of components as well as the unified method of assembly and alignment are described.


Tyrosine phosphorylation selectively regulates renal cellular phosphate transport. Evidence that it mediates the stimulatory effect of insulin-like growth factor-1.
The signal transduction mechanism responsible for the stimulation of the transport of inorganic phosphate (Pi) in response to mitogens is not known. In the present study, the changes in both Pi transport and tyrosine phosphorylation activity were determined in response to orthovanadate (VO4), an insulin-like agent and genistein, a specific inhibitor of tyrosine kinase activity. The results indicate that in opossum kidney epithelia, VO4 stimulated and genistein inhibited Pi transport dose dependently. The characteristics of the VO4 effect were quite similar to those described for insulin-like growth factor-1 (IGF-1) in terms of time course, selectivity (no effect on the Na-alanine transport), and dependency of the de novo synthesis of proteins. The effects of VO4 and IGF-1 on Pi transport, when tested at submaximal and maximal concentrations, respectively, were not additive suggesting that these two agents act through a common regulatory mechanism. As previously shown with IGF-1, the VO4 effect on Pi transport was additive to that of the maximal effect of Pi deprivation. Changes in tyrosine phosphorylation activity were tested in purified plasma membrane isolated from confluent OK cells using the polymer Glu:Tyr (4:1) as exogenous substrate. VO4 markedly enhanced whereas genistein inhibited the tyrosine kinase activity. The VO4 effect was dose dependent (0.1-1.0 mM), a concentration range similar to that eliciting the Pi transport response. The change in Pi transport was highly correlated with the variation in the tyrosine kinase activity induced by either vanadate (R = 0.969 P less than 0.01) or genistein (R = 0.992, P less than 0.01). In conclusion, VO4, an insulin-like agent and genistein, a specific inhibitor of tyrosine kinase activity selectively altered cellular Pi transport. These changes in Pi transport were associated with a dose-related alteration in tyrosine kinase activity measured in purified plasma membrane. The characteristics of the vanadate effects on Pi transport are similar to those reported for IGF-1 suggesting an important role of this signal transduction mechanism in mediating changes in Pi transport in response to mitogenic factors such as IGF-1.


New specific radioligand for one subpopulation of brain somatostatin receptors.
Cyclic octapeptide analogues of somatostatin (SS) like SMS 201-995 [H-(D) Phe-Cys-Phe-(D) Trp-Lys-Thr-Cys-Thr(ol)] or its Tyr3-derivative 204-090, displaced [125I-Tyr11]-SS 100% from pancreatic membranes but only 62-75% from brain membranes; the remaining sites were displaced by SS. These data indicate that some mini-somatostatins bind to a subpopulation of SS receptors in rat brain. The iodinated Tyr3-derivative (125I-204-090) can be considered a selective radioligand for one rat brain SS receptor subpopulation: It shows saturable and high affinity binding (KD = 0.29 nM; Bmax = 350 fmoles/mg protein) to rat cortex. The pharmacological properties of 125I-204-090 binding sites are similar to those of [125I-Tyr11]-SS sites. Distribution of these sites correspond to SS receptor-rich areas such as cortex, hippocampus, striatum, pituitary, pancreatic beta-cell. SS as well as SMS 201-995 bind to these sites with high affinity. The stability and high specific vs non-specific binding ratio makes 204-090 a radioligand of choice to measure this SS receptor subpopulation in CNS but also the SS receptors in pituitary and pancreas.


Vasopressor and Inotropic Management Of Patients With Septic Shock.
Numerous studies have evaluated the role of vasopressors and inotropes in the management of septic shock. This review assesses available evidence for the use of specific vasopressors in the management of septic shock. Use of adjunctive vasopressor therapy is also evaluated, examining the potential value of individual agents. Lastly, inotropic agents are evaluated for use in patients with myocardial dysfunction.


Loss of KLF4 and consequential downregulation of Smad7 exacerbate oncogenic TGF-β signaling in and promote progression of hepatocellular carcinoma.
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry. Cellular and molecular impacts of altered KLF4 expression and TGF-β signaling were determined using immunofluorescence, western blot, reverse-transcriptase PCR, chromatin immunoprecipitation and promoter reporter assays. Loss of KLF4 expression in primary HCC closely correlated with decreased Smad7 expression, increased p-Smad2/3 expression and independently predicts reduced overall and relapse-free survival after surgery. TGF-β signaling components were expressed in most HCC cells, and activation of TGF-β signaling promoted cell migration and invasion. Enforced KLF4 expression blocked TGF-β signal transduction and inhibited cell migration and invasion via activation of Smad7 transcription, whereas deletion of its C-terminal zinc-finger domain diminished this effect. KLF4 protein physically interacts with the Smad7 promoter. Promoter deletion and point mutation analyses revealed that a region between nucleotides -15 bp and -9 bp of the Smad7 promoter was required for the induction of Smad7 promoter activity by KLF4. Our data indicate that KLF4 suppresses oncogenic TGF-β signaling by activation of Smad7 transcription, and that loss of KLF4 expression in primary HCC may contribute to activation of oncogenic TGF-β signaling and subsequent tumor progression.


Feasibility of universal screening mammography. Lessons from a community intervention.
It is estimated that 44,500 American women will die of breast cancer in 1991. The breast cancer screening guidelines of the American Cancer Society and the National Cancer Institute calling for annual mammography for all women older than 50 years have been endorsed by numerous professional groups. Third-party reimbursement for screening mammography is becoming more prevalent, and payment for screening mammography is now a Medicare benefit. Our studies, conducted as part of a National Cancer Institute grant to increase the routine use of screening mammography and clinical breast examination in women 50 to 75 years of age, have uncovered a number of significant barriers to the implementation of screening guidelines among women, primary care physicians, and providers of mammography services. These barriers, as well as methods to assure the quality of mammography, need to be addressed before universal screening is feasible.


Quadriceps muscle energetics during incremental exercise in children and adults.
This study tested the hypothesis that the muscle metabolic responses of 9- to 12-yr-old children and young adults during incremental quadriceps exercise are dependent on age and sex. Fifteen boys, 18 girls, 8 men, and 8 women completed a quadriceps step-incremental test to exhaustion inside a magnetic resonance scanner for determination of the muscle metabolic responses using P-magnetic resonance spectroscopy. Quadriceps muscle mass was determined using magnetic resonance imaging scans enabling comparison of metabolic data at a normalized power output. The power output and the energetic state at the Pi/PCr and pH intracellular thresholds (IT) were independent of age and sex. The rate of change in Pi/PCr against power output after the ITPi/PCr (S2) was lower in boys (0.158 +/- 0.089) and girls (0.257 +/- 0.110) compared with men (0.401 +/- 0.114, P < 0.001) and women (0.391 +/- 0.133, P = 0.014), respectively, with sex differences present for children only (P = 0.003). Above the ITpH, S2 was more rapid in the men (-0.041 +/- 0.022, P = 0.003) and girls (-0.030 +/- 0.013, P = 0.011) compared with boys (-0.019 +/- 0.007), with no differences between the girls and the women (-0.035 +/- 0.015, P = 0.479). The increase in Pi/PCr at exhaustion was lower in boys (0.85 +/- 0.38) than that in men (1.86 +/- 0.65, P < 0.001) and in girls (1.78 +/- 1.25) than that in women (4.97 +/- 3.52, P = 0.003), with sex differences in both the child (P = 0.005) and the adult groups (P = 0.019). During moderate-intensity exercise, muscle metabolism appears adult-like in 9- to 12-yr-old children, although both age- and sex-related differences in the "anaerobic" energy turnover are present during high-intensity exercise.


Signal transduction for melatonin in human lymphocytes: involvement of a pertussis toxin-sensitive G protein.
We analyzed the melatonin signal transduction in human blood lymphocytes. High affinity melatonin receptors were identified by specific binding of 2-[125I]melatonin ([125I]MEL) to human lymphocyte membranes. Scatchard analysis of [125I]MEL binding revealed high affinity receptors, with a dissociation constant (Kd) of 0.45 nM and a binding capacity (Bmax) of 7.8 fmol/mg protein. Specific [125I]MEL binding was reduced markedly by GTP and its nonhydrolyzable analogues guanosine 5'-beta, gamma-imidotriphosphate (Gpp(NH)p) and guanosine 5'-O-(3-triphosphate) (GTP-gamma-S). Gpp(NH)p inhibited in a dose-dependent manner the [125I]MEL specifically bound to human lymphocyte membranes with a half-maximal inhibition (IC50) of 3.5 +/- 0.6 microM Gpp(NH)p. Treatment of human lymphocyte membranes with Gpp(NH)p increased the Kd value (Kd = 1.20 nM). Melatonin inhibited significantly and in a dose-dependent manner forskolin-stimulated cAMP production in intact human lymphocytes. Melatonin was able to stimulate diacylglycerol production in a dose-dependent manner in human lymphocyte membranes. Pertussis toxin treatment inhibited the specific [125I]MEL binding and blocked the ability of melatonin to both inhibit forskolin-stimulated cAMP production and stimulate diacylglycerol production. Pertussis toxin ADP-ribosylation and Western blot experiments demonstrated the protein expression of alpha i1/2, alpha i3/0, and beta gamma complexes of G proteins in human lymphocyte membranes. The results strongly suggest a pertussis toxin-sensitive melatonin signal transduction pathway in human lymphocytes that involves the inhibition of adenylyl cyclase and the stimulation of phospholipase C.


Construction and applications of a B vitamin genetic resource for investigation of vitamin-dependent metabolism in maize.
The B vitamins provide essential co-factors for central metabolism in all organisms. In plants, B vitamins have surprising emerging roles in development, stress tolerance and pathogen resistance. Hence, there is a paramount interest in understanding the regulation of vitamin biosynthesis as well as the consequences of vitamin deficiency in crop species. To facilitate genetic analysis of B vitamin biosynthesis and functions in maize, we have mined the UniformMu transposon resource to identify insertional mutations in vitamin pathway genes. A screen of 190 insertion lines for seed and seedling phenotypes identified mutations in biotin, pyridoxine and niacin biosynthetic pathways. Importantly, isolation of independent insertion alleles enabled genetic confirmation of genotype-to-phenotype associations. Because B vitamins are essential for survival, null mutations often have embryo lethal phenotypes that prevent elucidation of subtle, but physiologically important, metabolic consequences of sub-optimal (functional) vitamin status. To circumvent this barrier, we demonstrate a strategy for refined genetic manipulation of vitamin status based on construction of heterozygotes that combine strong and hypomorphic mutant alleles. Dosage analysis of pdx2 alleles in endosperm revealed that endosperm supplies pyridoxine to the developing embryo. Similarly, a hypomorphic bio1 allele enabled analysis of transcriptome and metabolome responses to incipient biotin deficiency in seedling leaves. We show that systemic pipecolic acid accumulation is an early metabolic response to sub-optimal biotin status highlighting an intriguing connection between biotin, lysine metabolism and systemic disease resistance signaling. Seed-stocks carrying insertions for vitamin pathway genes are available for free, public distribution via the Maize Genetics Cooperation Stock Center.


Stratified sampling design based on data mining.
To explore classification rules based on data mining methodologies which are to be used in defining strata in stratified sampling of healthcare providers with improved sampling efficiency. We performed k-means clustering to group providers with similar characteristics, then, constructed decision trees on cluster labels to generate stratification rules. We assessed the variance explained by the stratification proposed in this study and by conventional stratification to evaluate the performance of the sampling design. We constructed a study database from health insurance claims data and providers' profile data made available to this study by the Health Insurance Review and Assessment Service of South Korea, and population data from Statistics Korea. From our database, we used the data for single specialty clinics or hospitals in two specialties, general surgery and ophthalmology, for the year 2011 in this study. Data mining resulted in five strata in general surgery with two stratification variables, the number of inpatients per specialist and population density of provider location, and five strata in ophthalmology with two stratification variables, the number of inpatients per specialist and number of beds. The percentages of variance in annual changes in the productivity of specialists explained by the stratification in general surgery and ophthalmology were 22% and 8%, respectively, whereas conventional stratification by the type of provider location and number of beds explained 2% and 0.2% of variance, respectively. This study demonstrated that data mining methods can be used in designing efficient stratified sampling with variables readily available to the insurer and government; it offers an alternative to the existing stratification method that is widely used in healthcare provider surveys in South Korea.


Biocompatible antimicrobial colistin loaded calcium phosphate nanoparticles for the counteraction of biofilm formation in cystic fibrosis related infections.
The use of inhalable nanoparticles (NPs) for cystic fibrosis (CF) has been advocated as a promising tool to improve the efficacy of antimicrobials taking advantage of their ability to penetrate airway mucus and pathogen biofilm and to release the drug in or in proximity to the enclosed bacteria. Here, inhalable calcium phosphate (CaP) NPs were functionalized with colistin (Col) which is one of the most active antimicrobials against Gram-negative bacteria. The adsorption kinetic and isotherm of Col on CaP-NPs were investigated and fitted according to different mathematical models and revealed an electrostatic interaction between positively charged amine groups of Col and negatively charged surface of CaP-NPs. The maximum Col payload was of about 50 mg g-1 of CaP-NPs. After functionalization, despite an increase of size (213 vs 95 nm), in citrate solution, CaP-NPs maintained a dimension and surface charge considered suitable for crossing mucus barrier. CaP-NPs do not interact with mucin and are able to permeate a layer of artificial mucus. In vitro tests on pulmonary cells demonstrated that CaP-NPs are not cytotoxic up to a concentration of 125 μg mL-1. The antimicrobial and antibiofilm activity of Col loaded CaP-NPs tested on Pseudomonas aeruginosa RP73, a clinical strain isolated from a CF patient, was similar to that of free Col demonstrating that the therapeutic effect of Col adsorbed on CaP-NPs was retained. This work represents the first attempt to use CaP-NPs as delivery system for the CF treatment. The encouraging results open the way to further studies.


Normal blood supply to the uncus.
One hundred human brains, obtained from the routine autopsy service of the Dartmouth Medical School (Hanover, NH) and Rutland Hospital (Rutland, VT), were studied to establish a better understanding of the anatomy of the arterial supply to the uncus. Drawings of each dissection were made and the findings summarized. The variability in the number and size of the vessels to this region may be striking.


Preovulatory gonadotropin-releasing hormone surge in ovarian-intact rhesus macaques.
The occurrence and profile of the preovulatory hypothalamic GnRH surge in relation to plasma profiles of LH and ovarian steroids, i.e. 17 beta-estradiol (E2) and progesterone (P4), were examined in ovarian intact, freely moving rhesus macaques. Nine monkeys with active ovarian cycles were each fitted with a jugular venous catheter and two push-pull cannulae directed to separate sites within the median eminence (ME). Each female was connected continuously to a tether/swivel device through which daily blood samples or frequent blood samples and ME perfusates (simultaneously at 10- to 20-min intervals for 18-24 h) were obtained without disturbing the animals. An increment in the plasma E2 level (> 150 pg/ml) during the follicular phase (FP) was selected as the preovulatory ovarian signal and served as the index for initiating the ME push-pull perfusion (PPP). Daily increased P4 concentrations of more than 1 ng P4/ml plasma for several consecutive days were consistent with the assumption of ovulation and subsequent formation of a corpus luteum after PPP. A total of 18 PPP trials were completed; each in a fresh ME site. Five of these PPPs were performed during the mid- and late FP (3 were between 6-8 days before and 2 were 4 days before the E2 peak). The remaining 13 PPPs, each of 18- to 24-h duration, were performed between 24 h before and 48 h after the highest daily plasma E2 level, i.e. time zero. Of these 13 PPPs, 2 started within 12 h before (-12 to 0 h), 8 began within 12 h after (0-12 h), and 3 started between 12-24 h after this peak E2 value. During the FP, mean levels of GnRH and LH were less than 2 pg/ml and 20 ng/ml, respectively. During the periovulatory interval (-24 to 48 h around time zero), the release of hypothalamic GnRH (expressed in picograms per ml) increased to 6.63 +/- 2.35 between -12 to 0 h (n = 2), peaked at 20.70 +/- 6.09 between 0-12 h (n = 10), declined to 3.25 +/- 1.39 between 12-24 h (n = 11), and further declined to 0.89 +/- 0.18 between 24-36 h (n = 3). The mean GnRH value from 0-12 h was higher (P < 0.05) than other means (including those during the FP), except for the value between -12 to 0 h. Changes in mean plasma LH values during the same periods paralleled those in GnRH.(ABSTRACT TRUNCATED AT 400 WORDS)


Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL).
Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.


An increase in calcium influx contributes to post-tetanic potentiation at the rat calyx of Held synapse.
We studied the contribution of a change in presynaptic calcium influx to posttetanic potentiation (PTP) in the calyx of Held synapse, an axosomatic synapse in the auditory brain stem. We made whole cell patch-clamp recordings of a principal cell after loading of the presynaptic terminal with a calcium dye. After induction of PTP by a high-frequency train of afferent stimuli, the Fluo-4 fluorescence transients evoked by an action potential became on average 15 +/- 4% larger (n = 7). Model predictions did not match the fluorescence transients evoked by trains of brief calcium currents unless the endogenous calcium buffer had low affinity for calcium, making a contribution of saturation of the endogenous buffer to the synaptic potentiation we observed in the present experiments less likely. Our data therefore suggest that the increase of release probability during PTP at the calyx of Held synapse is largely explained by an increase in the calcium influx per action potential.


Effects of ethanol and basic fibroblast growth factor on the transforming growth factor beta1 regulated proliferation of cortical astrocytes and C6 astrocytoma cells.
The effects of ethanol on transforming growth factor beta1 (TGFbeta1)-regulated proliferation of primary cultured cortical astrocytes and C6 astrocytoma cells were determined. Cultured cells were treated with TGFbeta1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for as many as 4 days. The effects of these treatments on cell growth (the change in cell number) and cell proliferation (incorporation of [3H]thymidine) were determined. In addition, the effects of serum and basic fibroblast growth factor (bFGF) on TGFbeta1-affected cell proliferation were examined. Both TGFbeta1 and ethanol inhibited cell growth and proliferation among the two types of cells; this effect was only evident when the cells were grown in the presence of a mitogen, serum, or bFGF. When added together (either in a serum-supplemented or serum-free medium), however, TGFbeta1 and the mitogen effectively nullified each other. TGFbeta1 blocked the mitogenic effect of bFGF on astrocytes and C6 cells. Ethanol did not affect (i.e., neither added nor nullified) this antagonistic effect. TGFbeta1, like ethanol, is a potent anti-proliferative agent; either can nullify the mitogenic activity of serum or bFGF. Astrocytes and astrocyte-like cells react to combined TGFbeta1 and ethanol treatment differently than do neurons for which the inhibitory effects of TGFbeta1 and ethanol are additive.


[Nosocomial viral infections. Hepatitis, herpes and flu viruses].
Viruses account for about 5% of all nosocomial infections. Viral cross-infection is most common in infants and children, but also occurs in other groups, including the elderly, institutionalized persons of all ages, immunecompromised hosts, and patients with underlying chronic pulmonary, renal, or cardiac disease. These infections are associated with extended length of hospital stay, as well as considerable morbidity and mortality. The new technology of rapid viral diagnosis allows a more timely and accurate recognition of viral infections, even in the smaller hospital with limited laboratory resources. Early recognition of viral diseases should, in turn, permit the introduction, and further evaluation of specific measures for their control. Influenza vaccination of health care workers is an important prevention strategy for nosocomial infection.


Developing a new model for cross-cultural research: synthesizing the Health Belief Model and the Theory of Reasoned Action.
This article discusses the development of a new model representing the synthesis of two models that are often used to study health behaviors: the Health Belief Model and the Theory of Reasoned Action. The new model was developed as the theoretic framework for an investigation of the factors affecting participation by Mexican migrant workers in tuberculosis screening. Development of the synthesized model evolved from the concern that models used to investigate health-seeking behaviors of mainstream Anglo groups in the United States might not be appropriate for studying migrant workers or persons from other cultural backgrounds.


Genetic variations in microRNA-related genes are associated with survival and recurrence in patients with renal cell carcinoma.
We took a polygenic approach to evaluate the effects of 41 potentially functional single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs)-related genes on survival and recurrence among renal cell carcinoma (RCC) patients. During a median follow-up of 21.8 months, among 316 RCC patients, 64 died and 56 developed recurrence. In single-SNP analysis, we identified seven SNPs significantly associated with RCC survival and five SNPs with recurrence. The most significant associations were SNPs in GEMIN4 with the variant alleles of both rs7813 and rs910925 associated with 1.74-fold [95% confidence interval (CI) = 1.15-2.62] increased risk of death, whereas the variant allele of rs3744741 conferred a decreased risk of death [hazard ratio (HR) = 0.39; 95% CI = 0.19-0.77]. Several SNPs belonging to the pre-miRNA and were identified to be significantly associated with RCC recurrence. Haplotypes of DICER and DROSHA were also associated with altered patient survival and recurrence. More importantly, we observed cumulative effects of multiple SNPs on RCC survival. Compared with subjects carrying zero to two unfavorable genotypes, those carrying three to five and six and more unfavorable genotypes had an increased risk of death with a HR of 2.49 (95% CI = 1.24-5.00) and 6.66 (95% CI = 2.49-17.86), respectively, with significant dose-response trend (P for trend<0.001). As the first study of miRNA-related genetic polymorphisms on RCC clinical outcome, our results strongly suggested that miRNA-related SNPs may impact the recurrence and survival in RCC patients. Future investigation in larger populations and functional characterizations are necessary to validate these results.


[Complications of malignant tumors--malignant pleural effusions].
Malignant pleural effusion is a complication of malignant diseases that has an appreciable negative impact on the patient's quality of life. In view of the greatly reduced life expectancy of between 3 and 12 months (median), diagnostic and therapeutic management must be orientated to the principles of palliation. Diagnostic measures comprise cytological/histological confirmation of the malignant effusion and, where necessary, of the underlying malignant disease and the extent of the intrathoracic tumor growth. In view of the tendency of malignant pleural effusion to relapse, pleurodesis is indicated, which is most effectively accomplished by video-assisted thoracoscopic talcum poudrage.


Depressive symptoms and the self-reported use of alcohol, caffeine, and carbohydrates in normal volunteers and four groups of psychiatric outpatients.
The authors examined the relationship between depressive symptoms and the self-reported use of alcohol, carbohydrates, and caffeine in normal volunteers and four groups of psychiatric outpatients. Outpatients and normal volunteers were given a questionnaire asking about their use of each of the three substances in response to each of the 14 depressive symptoms on the Hamilton Rating Scale for Depression. They also rated how much each substance improved each symptom. Twenty-six normal volunteers, 35 patients with major depression, 117 patients with seasonal affective disorder, 16 patients with alcohol dependence, and 24 patients with comorbid primary depression and secondary alcohol dependence completed the questionnaire. Test-retest reliability was established. Analysis of variance and stepwise multivariate discriminant function analyses were used to determine if diagnostic groups differed in the reported use and effect of each of the three substances. The responses concerning use and effect of alcohol of patients with alcohol dependence with or without depression were indistinguishable from each other. The responses of the patient groups regarding caffeine and carbohydrate use did not differ from each other, but all differed significantly from the responses of normal volunteers. Discriminant function analysis distinguished alcoholics from nonalcoholics in the relationship between drinking and the symptoms of anger and anhedonia. The relationship between symptoms and substance use varied depending on the substance. Alcoholics without depression were as likely to report drinking in response to depressive symptoms as were those who had had depression. Patients of all diagnostic groups were more likely than normal volunteers to report using caffeine and carbohydrates in response to depressive symptoms.


Pyoderma caused by Proteus mirabilis in sheep.
Pyoderma is a purulent skin infection usually caused by bacteria and can be divided into primary and secondary categories based on histology. In the present study, an 18-month-old female mixed breed sheep was examined for pyoderma at the injection site of the enterotoxemia vaccine. After routine bacteriology and histopathology procedures, secondary pyoderma caused by Proteus mirabilis was diagnosed. The bacterium analysed using genome sequencing and new strain called AJJ 2021 was diagnosed. This is the first report of pyoderma caused by Proteus mirabilis in sheep.


Control by Phytochrome of Cytoplasmic Precursor rRNA Synthesis in the Cotyledons of Mustard Seedlings.
The influence of phytochrome (high irradiance reaction; operationally, continuous far red light) on the incorporation of [(3)H]uridine into the cytoplasmic 2.5 megadalton precursor rRNA in the cotyledons of mustard (Sinapis alba L.) seedlings has been investigated. After irradiating 36-hour-old etiolated seedlings with 12 hours of far red light, the rate of incorporation is stimulated about 2-fold, leading to 50% labeling of the precursor rRNA pool about 15 minutes after the tracer has reached the nucleotide precursor pool. In the dark control, there is a significantly smaller pool of precursor rRNA which is half-saturated with label only after about 27 minutes. Since neither the specific radioactivity of the UTP pool nor the processing of the precursor rRNA demonstrate a corresponding light-dependent change, it is concluded that phytochrome mediates an increase of the transcription of the rRNA genes. This gene activation accounts for the increased accumulation of mature cytoplasmic rRNA during the course of photomorphogenesis of the cotyledons.


Relational Agency of University Teachers of Chinese as a Second Language: A Personal Network Perspective.
Relational agency is pivotal for understanding how language teachers seek and utilize relational resources in different contexts and grow to be agents of change amid various educational challenges. This study explored how three university teachers of Chinese as a second language (CSL) enacted their relational agency to enhance their research capacity and sustain their professional development. Data on their personal network development was collected through concentric circle interviews, life-history interviews and written reflections over three months. Thematic analysis was adopted for iterative coding and interpretation of the data. The findings revealed that teachers' personal networks provided them with value guidance, emotional support and academic support, which exerted differential levels of impact on them to make agentic choices and actions. The study suggests that personal network analysis may serve as a suitable theoretical lens to achieve a multi-layered understanding of relational agency. The study also calls for more efforts to create learning opportunities and spaces in the relational context for teachers to build their career as agentic academics in language teacher education and development programs.


Photonic micro-electromechanical systems vibrating at X-band (11-GHz) rates.
We report on an opto-mechanical resonator with vibration excited by compressive radiation pressure via stimulated Brillouin scattering [SBS]. We experimentally excite a mechanical whispering-gallery mode (WGM) from an optical WGM and detect vibration via the red Doppler shifted (Stokes) light it scatters. We numerically solve the stress-strain equation to calculate the circumferentially circulating mechanical WGM and reveal mechanical WGMs with a variety of transverse shapes. Frequency in our device is limited by the shortest optical wavelength it can transmit, irrespective of device size.


A first synthesis of thiophene dendrimers.
[structure: see text] Thiophene dendrons and dendrimers were designed and synthesized using a convergent approach. Metal-mediated coupling reactions were used in the synthesis. A rational approach allowed the formation of alphaalpha, betabeta, and alphabeta linkages between the dendrons and thiophene units.


A perfluorochemical prevents ischemia-reperfusion injury of muscle.
This investigation evaluated the effect of oxygenated perfluorochemical (PFC) perfusion on the viability of ischemic skeletal muscle compared to hypothermic preservation. Twenty-five hindlimbs of 13 white rabbits were divided into five groups: a PFC group (7 hr of ischemia with 6 hr of PFC perfusion), a PFC/ reperfusion group (8 hr of ischemia with 6 hr of PFC perfusion and 1 hr reperfusion), a hypothermia group (7 hr of ischemia with 6 hr of 4 degrees C cold preservation), a hypothermia/reperfusion group (8 hr of ischemia with 6 hr of 4 degrees C cold preservation and 1 hr of reperfusion), and a control group. The levels of adenine nucleotides, creatine phosphate, hypoxanthine, xanthine, and lipid peroxide were determined in each group. In the PFC and PFC/reperfusion groups, the ATP level remained at 90% of that in the control group. The hypoxanthine level in the hypothermia/reperfusion group was decreased to 70% of that in the hypothermia group and the xanthine level was increased to 130%. In the PFC and PFC/reperfusion groups, hypoxanthine and xanthine levels were much lower and were similar to those in the control group. Lipid peroxide levels were also lower in the PFC and PFC/reperfusion groups than in the hypothermia/reperfusion group. Electron microscopy showed that endothelial cells from the PFC/reperfusion groups were not swollen. These results suggest that PFC perfusion is superior to hypothermia in inhibiting the generation of free radicals and in preventing ischemia-reperfusion injury of skeletal muscle.


Morbilliform Rash: An Uncommon Herald of SARS-CoV-2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first detected in Wuhan, China in 2019 after an outbreak of flu-like illness. The disease came to be known as the coronavirus disease of 2019 (COVID-19). It has spread quickly, spanning many countries, and has become a global pandemic. As this is a novel virus, its varied manifestations and symptomatology are coming to light daily. Although most threatening to the respiratory system, this virus has the propensity to affect multiple organ systems quickly leading to multi-organ dysfunction. Many dermatologic manifestations have been reported with no clear pattern. Most data have been anecdotal. Here we present a 78-year-old male who tested positive for SARS-CoV-2 with no usual symptoms that would alert one of the possibilities of COVID-19. He did, however, have a diffuse morbilliform rash most notable on the trunk and back. He went on to develop fever thereafter but did not develop any respiratory complications. The rash was short-lived and was treated with topical steroids and oral antihistamines. It is important to know and report new findings of novel diseases not only for diagnosis and treatment but also to place appropriate isolation precautions and containment. Rash may be the initial and sometimes the only manifestation of COVID-19.


An anti-nuclear antibody-negative patient with systemic lupus erythematosus (SLE) accompanied with anti-ribosomal P antibody (anti-P).
We report a case of an anti-nuclear antibody (ANA)-negative patient with systemic lupus erythematosus (SLE) accompanied with anti-phospholipid antibody syndrome (APS) and lupus nephritis (LN). Histological examination of placenta obtained by an artificially-induced abortion revealed multiple thromboses in the placental villi. Histology of biopsied kidney tissue revealed minimal change with deposits of immunoglobulin and complement. Anti-ribosomal P antibodies (anti-P) and lupus anticoagulant (LAC) were positive and anti-double stranded DNA antibody (anti-DNA) showed only a slightly positive titer in her serum. The intensity of proteinuria of the patient was correlated with the anti-P, but not anti-DNA titers.


Natriuria and calciuria levels in preeclampsia: a cross-sectional study.
Sodium excretion abnormalities in preeclampsia have been studied in relation to several factors. The objective of this study was to compare natriuria (mEq/24 h) and calciuria levels (mg/24 h) in preeclamptic patients. An analytical cross-sectional study with a control group was conducted in the obstetric center and the high-risk pregnancy outpatient clinic at a university hospital in southern Brazil, and in a primary healthcare unit in the same city, including pregnant women with mild preeclampsia, severe preeclampsia or chronic hypertension, and women with normal pregnancies (14 patients in each group). Natriuria was measured using an ion-selective electrode in an automated clinical chemistry analyzer (Hitache 917, Roche). All the patients collected 24-hour urine, at home or at the hospital, for analysis of proteins, creatinine, calcium, sodium and uric acid. Quantitative variables with asymmetrical distribution were described using the median, minimum and maximum, and were compared using the Kruskal-Wallis test. The results were logarithmically transformed, with one-way analysis of variance (ANOVA) by ranks and then the post-hoc Tukey test, and were analyzed by means of the Spearman correlation and receiver operating characteristic (ROC) curve. The significance level used was 0.05. There were significant differences between the groups in comparing severe preeclampsia with chronic hypertension and severe preeclampsia with controls (P < 0.0001 for both measurements). Natriuria levels may be lower in preeclampsia when associated with calciuria. Natriuria assessment is an additional test for differential diagnosis of hypertensive diseases in pregnancy, but is a poor predictor when used alone.


Primary hydatid cyst of the right maxillary sinus: a case report.
A hydatid cyst of the head and neck is a very rare condition, even in areas where Echinococcus infestation is endemic. We report a rare case of primary hydatid cyst of the right maxillary sinus in a 40-year-old man. The initial diagnosis of the presence of a cystic mass was the result of physical examination and computed tomography (CT) scan. We resected the cystic mass using the Caldwell-Luc procedure. A definitive diagnosis was confirmed by postoperative histopathologic examination. Hydatid cyst of the maxillary sinus is an extremely rare presentation. However, this condition should be considered in differential diagnosis of cystic lesions of the maxillary sinus.


Role of miR-132/methyl-CpG-binding protein 2 in the regulation of neural stem cell differentiation.
Methyl-CpG-binding protein 2 (MeCP2) is a well-known transcription repressor, and mutations in MECP2 cause serious neurological disorders. Many studies have suggested that MeCP2 is involved in neural maturation only, and have not reported its role in neural stem cell differentiation. In the present study, we investigated this possible role of MeCP2 in neural stem cells. We used two different differentiation methods to explore how MeCP2 influences neural stem cell differentiation. When we transfected MeCP2-overexpressing lentivirus into neural stem cells, astrocytic differentiation was impaired. This impaired astrocytic differentiation occurred even in conditions of 20% fetal bovine serum, which favored astrocytic differentiation. In addition, miR-132 had the largest expression change after differentiation among several central nervous system related miRNAs. A luciferase assay confirmed that miR-132 directly targeted MeCP2, and that miR-132 was able to reduce MeCP2 expression at both the RNA and protein levels. The upregulation of miR-132 by miRNA mimics promoted astrocytic differentiation, which was fully recovered by MeCP2 overexpression. These results indicate that miR-132 regulates cell lineage differentiation by reducing MeCP2. The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital of TongJi University, China (approval No. SHDSYY-2018-4748) on March 10, 2018.


Dental hygienists' knowledge of menopause and its potential oral manifestations.
The purpose of this study was to assess dental hygienists' general knowledge of menopause and its possible oral manifestations. Demographic descriptors, including education level, course work, and menopausal status, were examined to determine their influence on knowledge levels. A 27-item, self-administered survey was mailed to a random sample of Connecticut dental hygienists. Frequency distributions and inferential statistics (ANOVA, t-test) were used for data analysis. Fifty-four percent of respondents scored 75 percent or higher in general knowledge about menopause. Seven percent scored the same about its oral effects. Educational level and dental hygiene college curricula influenced the oral effect scores. Dental hygienists with bachelor degrees exhibited more knowledge than those with certificate/associate degrees. Those who had taken a college course on the oral effects of menopause had more knowledge than those who had not. The findings suggest that dental hygienists need more education about menopause and its related oral conditions. Those with additional knowledge might be more able to provide comprehensive care to menopausal and post-menopausal dental patients. Future research using larger sample sizes may enhance the education of dental hygienists in this area.


Repetitive Transcranial Magnetic Stimulation Modulates Frontal and Temporal Time-Varying EEG Network in Generalized Anxiety Disorder: A Pilot Study.
Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.


Zinc and flunitrazepam modulation of GABA-mediated currents in rat suprachiasmatic neurons.
The suprachiasmatic nucleus (SCN) of the hypothalamus is responsible for generating circadian rhythms in mammals, and GABA is the predominant neurotransmitter in the SCN. Properties of gamma-aminobutyric acid-A (GABAA) responses in SCN neurons were examined in acutely prepared hypothalamic slices from 3- to 8-wk-old rats with the use of whole cell voltage-clamp techniques. Zn2+ reduced the amplitude of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in a concentration-dependent manner ranging from a reduction of control amplitude to 88% at 10 microM to 27% at 1,000 microM. Zn2+ reduced IPSC amplitude to a similar degree in the presence of tetrodotoxin and also significantly reduced the amplitude of currents evoked by application of exogenous GABA (100 microM, pressure applied). Zn2+ increased the frequency of IPSCs at lower concentrations and decreased it at higher ones. Flunitrazepam (100 nM) usually failed to potentiate the amplitude of sIPSCs, but prolonged sIPSC kinetics. Two exponential components were normally resolved in the sIPSC decay constants, and flunitrazepam significantly increased those two components. Thus flunitrazepam increased the duration of sIPSCs and potentiated the amplitude of currents evoked by pressure application of GABA. Zn2+ and benzodiazepine each modulated the effect of GABA in nearly all cells, suggesting that most SCN neurons have a similar GABAA receptor subunit composition in this respect. Zn2+ also affected sIPSC frequency, which suggests that Zn2+ increased neuronal firing rate at lower concentrations. These results begin to define the cellular roles that these GABAA receptor modulators might play in circadian regulation.


Spray-driven halide exchange in solid-state CsPbX3 nanocrystal films.
CsPbI3 perovskite nanocrystals (NCs) are promising building blocks for photovoltaics and optoelectronics. However, they exhibit an essential drawback in the form of phase stability: α-phase, with a ∼1.80 eV bandgap, can easily experience a phase transition to a non-radiative orthorhombic δ-phase in an ambient environment. This leads to the need to carry out the CsPbI3-based device fabrication in an inert atmosphere, which is technologically inconvenient and expensive. One of the most successful approaches proposed to overcome this problem is synthesizing mixed halide CsPbBr3-xIx NCs to improve the stability of the α-phase perovskite structure. However, the formation of high-quality thin films of CsPbBr3-xIx NCs with high PLQY is challenging owing to the degradation of their optical properties after deposition on a substrate. This work presents spray coating to carry out a solid-state anion exchange in CsPbBr3 NCs thin films at ambient conditions with low-demanding reaction conditions. This constitutes a novel open-air and annealing-free technology to manufacture CsPbBr3-xIx NC thin films with high optical quality and record high photoluminescence quantum yields (PLQY) based on spray-driven halide (Br- to I-) anion exchange in a solid-state phase. Besides, tunable emission wavelengths between 520 and 670 nm can be obtained from CsPbBr3-xIx NC films using accurate tuning volumes of HI solution sprayed over the initial surface of CsPbBr3 film to provide the halide exchange. The optical quality of the halide-exchanged PNCs films remains practically identical to that of initial Br-containing layers, with a remarkable PLQY enhancement after anion exchange, from ∼61% for CsPbBr3 thin films emitting at 520 nm to ∼84% for mixed halide CsPbBr3-xIx film emitting at 640 nm. The huge potential of the system is confirmed by demonstrating a low-threshold amplified spontaneous emission.


Nephrectomy in an Asian small-clawed otter (Amblonyx cinereus) with pyelonephritis and hydronephrosis secondary to ureteral obstruction.
A 10-yr-old, captive, intact male Asian small-clawed otter (Amblonyx cinereus) with a history of bilateral nephrolithiasis was presented for acute-onset lethargy and inappetance of 5 days duration. On physical examination, the otter was about 8% dehydrated and a palpable fluid wave was present in the abdomen. An abdominal ultrasound revealed hydronephrosis of the left kidney and a hyperechoic structure present within the lumen of the left ureter, causing an obstruction. A urinalysis revealed struvite crystalluria, bacteriuria, and an elevated pH. Following 4 days of antibiotic therapy, a left ureteronephrectomy was performed. Upon opening the kidney to retrieve calculi, a large amount of purulent material was noted within the renal pelvis. To the authors' knowledge, this is the first documented case of a nephrectomy in an Asian small-clawed otter. Nephrectomy should be considered as a viable option for treatment of ureteral obstruction, hydronephrosis, or severe pyelonephritis.


Contracted Nose after Silicone Implantation: A New Classification System and Treatment Algorithm.
Silicone implants are frequently used in augmentation rhinoplasty in Asians. A common complication of silicone augmentation rhinoplasty is capsular contracture. This is similar to the capsular contracture after augmentation mammoplasty, but a classification for secondary contracture after augmentation rhinoplasty with silicone implants has not yet been established, and treatment algorithms by grade or severity have yet to be developed. Photographs of 695 patients who underwent augmentation rhinoplasty with a silicone implant from May 2001 to May 2015 were analyzed. The mean observation period was 11.4 months. Of the patients, 81 were male and 614 were female, with a mean age of 35.9 years. Grades were assigned according to postoperative appearance. Grade I was a natural appearance, as if an implant had not been inserted. Grade II was an unnatural lateral margin of the implant. Clearly identifiable implant deviation was classified as grade III, and short nose deformation was grade IV. Grade I outcomes were found in 498 patients (71.7%), grade II outcomes in 101 (14.5%), grade III outcomes in 75 (10.8%), and grade IV outcomes in 21 patients (3.0%). Revision surgery was indicated for the 13.8% of all patients who had grade III or IV outcomes. It is important to clinically classify the deformations due to secondary contracture after surgery and to establish treatment algorithms to improve scientific communication among rhinoplasty surgeons. In this study, we suggest guidelines for the clinical classification of secondary capsular contracture after augmentation rhinoplasty, and also propose a treatment algorithm.


Left atrial pressure can be accurately transmitted to the pulmonary artery despite zone 1 conditions.
Pulmonary arterial occlusion pressure is not thought to reflect left atrial pressure (Pla) when alveolar pressure (PA) exceeds pulmonary venous pressure because alveolar capillaries collapse and the required continuous fluid column between the pulmonary artery and left atrium is interrupted. However, arterial-to-venous flow can occur when PA exceeds both the pulmonary arterial pressure (Ppa) and pulmonary venous pressure (i.e., in Zone 1 conditions), indicating the existence of a continuous patent vascular channel. Accordingly, Ppa should reflect Pla under these conditions. To investigate this connection cannulas were placed in the pulmonary arteries and left atria of eight excised rabbit lungs. Ppa and Pla were set 5 cm H2O above PA, which ranged from 0 to 25 cm H2O. Pla was then reduced in 2 to 4 cm H2O decrements while recording Ppa when arterial-to-venous flow ceased. At all PAs greater than 0 cm H2O, Pla was accurately reflected by the Ppa when both were exceeded by PA. The greater the PA, the lower the Ppa could track Pla below PA. Pla can be accurately measured by a pulmonary arterial catheter under Zone 1 conditions.


Novel BCR-ABL1 fusion and leukemic mutations of SETBP1, PAX5, and TP53 detected by next generation sequencing in chronic myeloid leukemia.
Patients with BCR-ABL1 fusion genes are potential candidates for targeted therapy with tyrosine kinase inhibitor (TKI) imatinib. However, novel BCR-ABL1 fusion variants can be undetected by qRT-PCR-based routine molecular screening, affecting immediate patient management and proper treatment selection. In this study, we describe a case of chronic myeloid leukemia (CML) harboring a novel BCR-ABL1 variant gene. Although Fluorescent In situ Hybridization (FISH) analysis suggested Philadelphia (Ph) translocation, qRT-PCR screening failed to detect the presence of a functional fusion transcript, which is critical for selecting targeted therapy against BCR-ABL1 fusion with aberrant kinase activity. Meanwhile, G-band cytogenetic analysis was performed twice without a solid conclusion. To overcome the uncertainty whether TKIs should be used to treat this patient effectively, we performed whole genome sequencing (WGS) in a next-generation sequencing (NGS) platform and discovered an unusual e13a2-like BCR-ABL1 fusion with 9 ABL1 intron 1 nucleotides incorporated into the broken BCR exon 13 to form a novel chimeric exon, which has never been described previously based on the best of our knowledge. Based on FISH and NGS results, the patient was treated with imatinib, showing significant improvement. Moreover, we also detected novel genetic mutations in the known leukemic genes SETBP1, PAX5, and TP53, while their role in the leukemogenesis remains to be determined. In summary, we have identified BCR-ABL1 fusion and other genetic mutations in a diagnostically difficult case of CML, demonstrating that NGS is a powerful diagnostic tool when routine procedures are challenged.


Deep sea Syllidae (Annelida, Phyllodocida) from Southwestern Atlantic.
We describe herein ten species of Syllidae from the Southern Brazil continental slope (700-2000 m deep), belonging to the genera Anguillosyllis, Exogone, Parexogone, Prosphaerosyllis, Sphaerosyllis and Syllis. Out of those, three species are new to science and six are formally reported for Brazil for the first time. Some synonymies are proposed and a taxonomic key for all described species of the genus Anguillosyllis is provided.


Validation of the Chinese version of joint protection self-efficacy scale in patients with rheumatoid arthritis.
To develop and validate the Chinese version of the Joint Protection Self-Efficacy Scale (CJP-SES) in patients with rheumatoid arthritis (RA) in China. (1) Translation of the original German/English version JP-SES and cultural adaptation into the Chinese language; (2)Validation of the CJP-SES with the Chinese versions of the Arthritis Self-Efficacy Scale-8 (ASES-8), the Laffrey Health Conception Scale (LHCS), 10-item Perceived Efficacy in Patient-Physician Interactions Scale (PEPPI-10), Disease Activity Score-28 (DAS-28) and Health Assessment Questionnaire (HAQ). Instrument measurement included reliability testing, item generation, construct validity, test-retest reliability, and correlation with other measurements. Confirmatory factor analysis was applied to determine construct validity and internal consistency. One hundred fifteen patients with RA were investigated. Finally, 105 RA patients were included in the analysis. Confirmatory factor analysis demonstrated fit for a unidimensional model of the JP-SES. Additionally, the scale showed internal consistency (Cronbach's α coefficient 0.922), kappa coefficient (0.653), and test-retest reliability (ICC = 0.94). Weak correlations with other scores for the other instruments, such as the Chinese version of ASES-8 (0.263) and PEPPI-10 (0.326). Correlation with duration (0.274), moderate correlation with BMI (- 0.438) and DAS-28 (- 0.493), and strong correlation with HAQ (- 0.644) were found in this research. This is the first study to adapt and validate the JP-SES into Chinese for use in patients with RA. Our research showing that the CJP-SES has a good construct validity, internal consistency, and test-retest reliability. This scale can help doctors and nurses to assess the self-efficacy of patients with RA. ClinicalTrials.gov Identifier: TJYY-YLS-036.


Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells.
The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells.