Outcome of Childhood Cerebellar Pilocytic Astrocytoma: A Series With 20 Years of Follow Up.
Cerebellar pilocytic astrocytoma (PCA) is one of the few CNS tumors that can be cured with gross-total removal (GTR). In this series, we had 39 patients diagnosed with cerebellar PCA, 27 patients (70%) had GTR, and mean follow-up period was 62 months with no tumor recurrence. To assess the long-term outcome of childhood cerebellar PCA treated at our institute during the period 2000-2020 and to highlight our surgical protocol. Retrospective review of all patients under 18 years of age who were diagnosed with cerebellar PCA and had surgical excision between 2000 and 2020 at the Medical City of King Saud University. The study included 39 patients: 17 males and 22 females, the mean age was 8.4 years. Radiologically, the tumor was solid in eight patients, cystic in 15 patients, and mixed components were found in 16 patients. The lesion was located in the right cerebellar hemisphere in 12 patients, left cerebellar hemisphere in five patients, and midline 22 patients. The tumor size ranged from 2 to 7 cm in its greatest diameter, it was <5 cm in 13 patients and >5 cm in 26 patients. Thirty-one patients had preoperative hydrocephalus. GTR of the tumor was achieved in 27 patients and subtotal resection (STR) was done in 12 patients, 18 patients required permanent ventriculoperitoneal (V-P) shunt, and five patients had postoperative radiotherapy. Postoperative complications included infection in two patients, cerebellar mutism in two patients, and significant neurologic disability in four patients. The duration of follow-up ranged from 0 to 240 months (mean follow-up period: 62.0 months). The outcome at 10 years was good in 30 patients, fair in four patients, poor in four patients, and one patient died. Recurrence was documented in nine patients, seven of them had GTR and two had STR. GTR, if achievable, is curative for childhood cerebellar PCA. Many posterior fossa surgical complications could be avoided with watertight dural closure. Although new dural substitutes are available we prefer using autologous grafts (pericranium). It is easy to harvest pericranial graft from the external ventricular drain (EVD) site. The insertion of EVD synchronously with GTR of the tumor and gradual weaning of EVD could avoid the insertion of V-P shunt.


Implementing the MMA.
A lot has been written about the adequacy of the drug benefit in the new Medicare Prescription Drug, Improvement, and Modernization Act (MMA) and the political arm-twisting needed to get the legislation through Congress.


Budget Impact Analysis of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Asthma in the Dubai Academic Healthcare Corporation.
Asthma is a common, chronic respiratory disorder associated with substantial societal and economic burden globally, despite the availability of different treatment modalities. GSK has developed a once-daily single-inhaler triple therapy (SITT), comprised of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI); a combination of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist for patients with uncontrolled asthma. A budget impact analysis was conducted to determine the financial impact of introducing FF/UMEC/VI SITT from the perspective of the Dubai Academic Healthcare Corporation (DAHC). A budget impact model was constructed using an epidemiology-based approach and used to estimate the expected 5-year budget impact of including FF/UMEC/VI for the treatment of eligible patients within the DAHC in the United Arab Emirates (UAE). The model included both pharmacy and efficacy-related costs. The perspective of the DAHC healthcare payer was adopted, thus only direct payer costs were included in the analysis. A one-way sensitivity analysis was conducted to test the robustness of the model structure, assumptions, and input parameters. The total budget impact was estimated to save 1 million United States Dollars (USD) over 5 years, with budget impacts of 0.08 million USD in Year 1; 0.14 million USD in Year 2; 0.22 million USD in Year 3; 0.28 million USD in Year 4; and 0.33 million USD in Year 5. The overall budget impact per patient was estimated to save 12.2 USD over 5 years. In one-way sensitivity analyses, the budget impact was most sensitive to changes in the market uptake of FF/UMEC/VI. Healthcare payers may consider FF/UMEC/VI in the management of uncontrolled asthma which would save costs and reduce healthcare resource use in the UAE.


Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.
We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).


[Incidence of thyroid cancer in children and adolescents in Białorus after the Chernobyl catastrophe in 1986].
Fifteen years after Chernobyl nuclear plant catastrophe thyroid cancer was diagnosed in 882 persons among the group of 2,618,482 persons aged 6-18 years. The radioactive contamination, mainly with isotopes of radioactive iodine, seems to be a major cause of such a high incidence of thyroid cancer in children and adolescents. However, it is necessary to consider other factors which also might influence the process of transformation of the thyroid cells to the thyroid cancer. The iodine deficiency in environment was recognized as an important factor. Therefore, the countrywide programme of the investigations of iodine deficiency and goiter prevalence was established in the Republic of Belarus with the assistance of WHO Office for Europe. Within this program the examination of 11,562 children and adolescents aged 6-18 years from 30 schools in urban and rural areas was performed. The results obtained are typical for significant iodine deficiency and moderate goiter endemy. The analysis of these two factors and their influence on the incidence and distribution of thyroid cancer in different regions of Belarus is a subject of this paper. It is worth adding that 15 years after the catastrophe a visible rise in the number of thyroid cancers is noted in the group of adolescents and adults.


Somatostatin in the ovary of an African lungfish (Protopterus annectens): an in situ hybridisation, immunohistochemical, and autoradiographical study.
In mammals, somatostatin seems to be involved in the control of ovarian steroidogenesis. There have been no studies on the presence or actions of somatostatin in the ovary of nonmammalian vertebrates. The localisation of somatostatin-14 was examined immunohistochemically using the antibody to somatostatin-14 in the ovary of the African lungfish Protopterus annectens. Immunoreactivity was present in the granulosa cells of mature ovarian follicle examined by light microscopy. Using an oligonucleotide probe complementary to mRNA for somatostatin-14 and labelled at the 3'-end with alpha-35S, in situ hybridisation demonstrated somatostatin-14 mRNA distributed in cells showing the same localisation as that of the immunoreactive cells. Binding sites for SST-14 were identified with autoradiography using [125I]somatostatin-14. Binding sites were localised on granulosa and theca cells. Somatostatin-14 may be thus synthesised in the lungfish ovary.


Intrinsic susceptibility and bond defects in the novel two dimensional frustrated antiferromagnet Ba2Sn2ZnCr7pGa10-7pO22.
We present microscopic and macroscopic magnetic properties of the highly frustrated antiferromagnet Ba(2)Sn(2)ZnCr(7p)Ga(10-7p)O22, respectively, probed with NMR and SQUID experiments. The T variation of the intrinsic susceptibility of the Cr3+ frustrated Kagomé bilayer, chi(Kag), displays a maximum around 45 K. The dilution of the magnetic lattice has been studied in detail for 0.29</=p</=0.97. Novel dilution independent defects, likely related with magnetic bond disorder, are evidenced and discussed. We compare our results to SrCr(9p)Ga(12-9p)O19. Both bond defects and spin vacancies do not affect the average susceptibility of the Kagomé bilayers.


[Xuanju compound capsule combined with erogenous focus exercise is effective for premature ejaculation].
To investigate the effect of the Chinese medicine Xuanju compound capsule combined with erogenous focus exercise on premature ejaculation. Fifty-two patients with premature ejaculation were divided into a treatment group (n = 28) and a control group ( n = 24) , both treated by erogenous focus exercise and the former given Xuanju compound capsule in addition. After four weeks of treatment, comparisons were made of the sexual satisfaction between the two groups. The cure rate and the rate of improvement of sexual satisfaction were 21.43% and 67. 86% respectively in the treatment group, significantly higher than in the control group. Xuanju compound capsule combined with erogenous focus exercise is highly effective in the treatment of premature ejaculation, with few adverse effects.


DedA protein relates to action-mechanism of halicyclamine A, a marine spongean macrocyclic alkaloid, as an anti-dormant mycobacterial substance.
A macrocyclic alkaloid, halicyclamine A, was re-discovered from an Indonesian marine sponge of Haliclona sp. 05A08 as an anti-dormant mycobacterial substance. To clarify action-mechanism of halicyclamine A, halicyclamine A-resistant strains were screened from the transformants of Mycobacterium smegmatis with the genomic DNA library of M. bovis BCG, which were constructed in the multi-copy shuttle cosmid pYUB145. Sequencing analysis of the cosmids isolated from the halicyclamine A-resistant transformants revealed that the responsible gene was involved in the genome region between 2920.549 kb and 2933.210 kb. Further experiments using the transformants over-expressing individual gene contained in the responsible region were executed, and the transformant, which over-expressed BCG2664 gene assigned as dedA gene, was found to become halicyclamine A-resistant. This evidence strongly suggested that DedA protein correlates with the action-mechanism of halicyclamine A as an anti-dormant mycobacterial substance.


Periapical status, quality of root canal fillings and estimated endodontic treatment needs in an urban German population.
The objective of this study was to determine the periapical status and the quality of root canal fillings and to estimate the endodontic treatment needs in a German population. Clinical and radiographic data and the operative procedures performed were evaluated on 323 patients coming to a dental surgery in Stuttgart, Germany, in 1993. In 182 individuals at least one tooth exhibited a root canal filling, a necrotic pulp or an irreversible pulpitis. Out of the 7897 teeth examined, 215 (2.7%) had a root canal treatment (category A), 122 being non-endodontically treated (1.5%) did not respond to the sensitivity test (category B) and 53 (0.7%) were diagnosed as having irreversible inflamed pulp tissue (category C). The prevalence of teeth associated with radiographic signs of periapical pathosis was 61% in the group of root canal filled teeth and 88% in the group of pulpless and non-endodontically treated teeth. Using the level and the density of the root canal filling as criteria for evaluating the technical standard, only 14% of the endodontic treatments of non-apicectomized teeth were qualified as adequate. The minimal endodontic treatment need is 2.3% related to all examined teeth when the root canal filled teeth with clinical symptoms of periapical periodontitis (category A) and those of categories B and C are included. The real endodontic treatment need is suggested to be larger when considering that the technical quality of the obturation is poor in most symptomless endodontically treated teeth associated with a periapical lesion. In the case of retreatment of these teeth, the endodontic treatment need would then be calculated at 3.7%.


Finite-size analysis of a two-dimensional Ising model within a nonextensive approach.
In this work we present a thorough analysis of the phase transitions that occur in a ferromagnetic two-dimensional Ising model, with only nearest-neighbors interactions, in the framework of the Tsallis nonextensive statistics. We performed Monte Carlo simulations on square lattices with linear sizes L ranging from 32 up to 512. The statistical weight of the Metropolis algorithm was changed according to the nonextensive statistics. Discontinuities in the m(T) curve are observed for q< or =0.5 . However, we have verified only one peak on the energy histograms at the critical temperatures, indicating the occurrence of continuous phase transitions. For the 0.5<q< or =1.0 regime, we have found continuous phase transitions between the ordered and the disordered phases, and determined the critical exponents via finite-size scaling. We verified that the critical exponents alpha , beta , and gamma depend on the entropic index q in the range 0.5<q< or =1.0 in the form alpha(q)=(10q2-33q+23)/20 , beta(q)=(2q-1)/8 , and gamma(q)=(q2-q+7)/4 . On the other hand, the critical exponent nu does not depend on q . This suggests a violation of the scaling relations 2beta+gamma=dnu and alpha+2beta+gamma=2 and a nonuniversality of the critical exponents along the ferro-paramagnetic frontier.


Haploinsufficiency of Runx1 results in the acceleration of mesodermal development and hemangioblast specification upon in vitro differentiation of ES cells.
The AML1 gene (recently renamed Runx1), which encodes the DNA-binding subunit of a transcription factor of the core binding factor (CBF) family, is required for the establishment of definitive hematopoiesis. We have previously demonstrated that Runx1 is expressed in yolk sac mesodermal cells prior to the establishment of the blood islands and in the embryoid body (EB)-derived blast-colony-forming cells (BL-CFCs), the in vitro equivalent of the hemangioblast. Analysis of Runx1-deficient embryonic stem (ES) cells demonstrated that this gene is essential for the generation of normal numbers of blast colonies, the progeny of the BL-CFCs. In the present study, we analyzed the potential of Runx1(+/-) ES cells to determine if heterozygosity at the Runx1 locus impacts early developmental events leading to the commitment of the BL-CFCs. Our results indicate that Runx1 heterozygosity leads to an acceleration of mesodermal commitment and specification to the BL-CFCs and to the hematopoietic lineages in EBs.


The Application of DNA Barcodes for the Identification of Marine Crustaceans from the North Sea and Adjacent Regions.
During the last years DNA barcoding has become a popular method of choice for molecular specimen identification. Here we present a comprehensive DNA barcode library of various crustacean taxa found in the North Sea, one of the most extensively studied marine regions of the world. Our data set includes 1,332 barcodes covering 205 species, including taxa of the Amphipoda, Copepoda, Decapoda, Isopoda, Thecostraca, and others. This dataset represents the most extensive DNA barcode library of the Crustacea in terms of species number to date. By using the Barcode of Life Data Systems (BOLD), unique BINs were identified for 198 (96.6%) of the analyzed species. Six species were characterized by two BINs (2.9%), and three BINs were found for the amphipod species Gammarus salinus Spooner, 1947 (0.4%). Intraspecific distances with values higher than 2.2% were revealed for 13 species (6.3%). Exceptionally high distances of up to 14.87% between two distinct but monophyletic clusters were found for the parasitic copepod Caligus elongatus Nordmann, 1832, supporting the results of previous studies that indicated the existence of an overlooked sea louse species. In contrast to these high distances, haplotype-sharing was observed for two decapod spider crab species, Macropodia parva Van Noort & Adema, 1985 and Macropodia rostrata (Linnaeus, 1761), underlining the need for a taxonomic revision of both species. Summarizing the results, our study confirms the application of DNA barcodes as highly effective identification system for the analyzed marine crustaceans of the North Sea and represents an important milestone for modern biodiversity assessment studies using barcode sequences.


Psychosocial Adjustment in Ugandan Children: Coping With Human Immunodeficiency Virus Exposure, Lifetime Adversity, and Importance of Social Support.
Cumulative lifetime adversity and social support were investigated as determinants of psychosocial adjustment (esteem, distress, hopefulness, positive outlook/future aspirations, and sense of purpose) over 12 months in 6-10-years-old HIV-infected, HIV-exposed uninfected and HIV-unexposed uninfected children from Uganda. Each determinant and psychosocial adjustment indicator was self-reported using standardized questionnaires administered at baseline, 6, and 12 months. Linear mixed effects models were used to relate time-varying lifetime adversity and social support to psychosocial adjustment over 12 months. Regardless of HIV status, higher adversity predicted lower esteem (coefficient b = -2.98, 95% confidence interval (CI): [-4.62, -1.35]) and increased distress (b =3.96, 95% CI: [1.29, 6.62]) but was not associated with hopefulness, positive outlook or sense of purpose. Low social support predicted higher distress (b =9.05, 95% CI: [7.36, 10.73]), lower positive outlook (b = -10.56, 95% CI: [-2.34, -8.79]) and low sense of purpose (b = -9.90, 95% CI: [-11.44, -8.36]) over 12 months. Pragmatic interventions that enhance coping with adversity and provide emotional/instrumental support should be tested for effectiveness in promoting resilient psychosocial adjustment trajectory in vulnerable children.


[Changes of paradigms in psychiatry].
During the last centuries mental illnesses represented brain disorder. About hundred years ago--instead of gradually accumulating neurophysiological knowledge--the focus of attention shifted to investigation of abnormal mental states divorced from cerebral function. The advance of the brain research and psychopharmacology has been progressively narrowing the marked demarcation between organic and functional (psychogenic) syndromes. Till the end of the seventies the psychotic patients were treated in closed mental wards, the neurotics in open neurological ones in the common departments for neurology and psychiatry. The modernization of the mental care system started when psychiatry became independent of the neurology. The psychotherapy-despite of the international acknowledgement of the Hungarian psychoanalysts-has developed only in the last third of this century. The opposition of the biological and psychodynamic approaches theoretically refer to the presumed physical or mental origin, whereas mental function means the summation of variety of electrical and chemical events occurring in the brain. The asylums have gradually progressed to the open wards and therapeutic communities. Beside of the hospital treatment the outpatient care became a matter of primary importance, but the system of out-of-hospital alternatives, day-hospitals, halfway institutes, patient's homes, work places have been lacking. The modern psychiatric care system is moving forward the community in spite of its resistance. The psychiatric patients suffer not only from their mental symptoms and experienced disability, but mainly from the unfavorable attitudes of the immediate and social environment. The biological, psychological and sociological factors determine the origin, the treatment and the outcome of the mental disorders; neither of them can neglect without disadvantage of the other two.


The effects of anticancer drugs on levels of nitric oxide and adrenomedullin.
Nephrotoxicity is one of the most important complications of anticancer treatment. Ifosfamide, platinum and methotrexate (MTX) affect renal tubular epithelial cells. Nitric oxide (NO) serves many functions within the kidney. Adrenomedullin (AM) is a potent vasodilator peptide, and may function as a circulating hormone and an autocrine/paracrine mediator involved in the regulation of the cardiovascular system, blood pressure, and renal function. It also has a renoprotective effect and inhibits the generation of reactive oxygen metabolites. To our knowledge, no studies have investigated the effects of anticancer drugs on levels of AM and NO. We investigated the effects of these drugs on the levels of AM and total nitrite, a stable product of NO, and their relations to renal functions. The study was performed in 18 patients (13 males, 5 females) who received chemotherapeutic regimens including high-dose MTX or ifosfamide and platinum. Total nitrite was quantitated by means of the Griess reaction, while AM level was measured by high performance liquid chromatography (HPLC). Plasma total nitrite level (micromol/L) was decreased after chemotherapy (78.73 +/- 47.28 vs. 46.69 +/- 13.89, p: 0.002). A statistically significant difference was found between fractional excretion (FE) of total nitric oxide (FE(NO)) before and after chemotherapy (25.89 +/- 23.11 vs. 51.74 +/- 40.01, p: 0.008). The differences in plasma AM levels (pmol/ml) before (25.07 +/- 4.98) and after (30.20 +/- 1.39) chemotherapy were also statistically significant (p: 0.005). FE(AM) after chemotherapy (1.41 +/- 1.01) was found to be higher than before chemotherapy (0.64 +/- 0.43) (p: 0.000). Our results indicate that some chemotherapeutic agents (high-dose MTX, ifosfamide, and cisplatinium) may cause renal tubular damage. FE(AM) and FE(NO) may also be used for the detection of subclinical acute tubular nephrotoxicity. However, further detailed researches will be necessary to establish the certain role of NO and AM in toxicities of chemotherapeutic agents.


Proteome analysis of apoptotic cells.
Apoptosis, a genetically determined form of cell death, is a central and complex process involved in the development of multicellular organisms in the maintenance of cell homeostasis. During apoptosis, a large number of proteins involved in transducing signals are posttranslationally modified. Classical proteomics, the combination of protein separation by two-dimensional gel electrophoresis (2DGE) and protein identification by mass spectrometry (MS), enabled the discovery of more than 100 proteins altered during apoptosis. Functional data about protein degradation, modification, translocation, and synthesis were obtained. In addition to classical proteomics, some specifically designed proteome studies were carried out to analyze specific apoptotic components such as the mitochondrial releasing factors, death-inducing signaling complex (DISC), inhibitor of apoptosis (IAP) interacting proteins, and caspases. The identification of main regulators significantly influenced the elucidation of the concept underlying apoptosis signaling. Thus, the application of detailed protein analytical methods in the young field of apoptosis research was particularly fruitful.


Chylous ascites: a rare complication of vagotomy. Case report.
A previously healthy 30-year-old man underwent vagotomy and pyloroplasty for a chronic duodenal ulcer that had not responded to H2 blockers. On the third day his abdomen was slightly distended; this gradually increased and on the eighth day ascites was confirmed by ultrasonography. Paracentesis yielded 4 litres of milky, odorless fluid. He was treated by fat free diet as he refused parenteral nutrition and on day 15 a further two litres of fluid were withdrawn, this time straw coloured. By day 31 his abdomen had returned to normal and his serum albumin concentration (which had dropped to 26 g/l) had risen to 43 g/l. He has now remained well for two years. Chylous ascites is a rare complication of truncal vagotomy, but should be suspected if postoperative ascites develops. Early recognition and treatment are important.


Survey design for lakes and reservoirs in the United States to assess contaminants in fish tissue.
The National Lake Fish Tissue Study (NLFTS) was the first survey of fish contamination in lakes and reservoirs in the 48 conterminous states based on a probability survey design. This study included the largest set (268) of persistent, bioaccumulative, and toxic (PBT) chemicals ever studied in predator and bottom-dwelling fish species. The U.S. Environmental Protection Agency (USEPA) implemented the study in cooperation with states, tribal nations, and other federal agencies, with field collection occurring at 500 lakes and reservoirs over a four-year period (2000-2003). The sampled lakes and reservoirs were selected using a spatially balanced unequal probability survey design from 270,761 lake objects in USEPA's River Reach File Version 3 (RF3). The survey design selected 900 lake objects, with a reserve sample of 900, equally distributed across six lake area categories. A total of 1,001 lake objects were evaluated to identify 500 lake objects that met the study's definition of a lake and could be accessed for sampling. Based on the 1,001 evaluated lakes, it was estimated that a target population of 147,343 (+/-7% with 95% confidence) lakes and reservoirs met the NLFTS definition of a lake. Of the estimated 147,343 target lakes, 47% were estimated not to be sampleable either due to landowner access denial (35%) or due to physical barriers (12%). It was estimated that a sampled population of 78,664 (+/-12% with 95% confidence) lakes met the NLFTS lake definition, had either predator or bottom-dwelling fish present, and could be sampled.


Exploring the in vitro and in vivo compatibility of PLA, PLA/GNP and PLA/CNT-COOH biodegradable nanocomposites: Prospects for tendon and ligament applications.
Anterior cruciate ligament (ACL) reconstructive surgeries are the most frequent orthopedic procedures in the knee. Currently, existing strategies fail in completely restoring tissue functionality and have a high failure rate associated, presenting a compelling argument towards the development of novel materials envisioning ACL reinforcement. Tendons and ligaments, in general, have a strong demand in terms of biomechanical features of developed constructs. We have previously developed polylactic acid (PLA)-based biodegradable films reinforced either with graphene nanoplatelets (PLA/GNP) or with carboxyl-functionalized carbon nanotubes (PLA/CNT-COOH). In the present study, we comparatively assessed the biological performance of PLA, PLA/GNP, and PLA/CNT-COOH by seeding human dermal fibroblasts (HFF-1) and studying cell viability and proliferation. In vivo tests were also performed by subcutaneous implantation in 6-week-old C57Bl/6 mice. Results showed that all formulations studied herein did not elicit cytotoxic responses in seeded HFF-1, supporting cell proliferation up to 3 days in culture. Moreover, animal studies indicated no physiological signs of severe inflammatory response after 1 and 2 weeks after implantation. Taken together, our results present a preliminary assessment on the compatibility of PLA reinforced with GNP and CNT-COOH nanofillers, highlighting the potential use of these carbon-based nanofillers for the fabrication of reinforced synthetic polymer-based structures for ACL reinforcement. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2182-2190, 2017.


Long-period fiber grating sensors for the measurement of liquid level and fluid-flow velocity.
This paper presents the development and assessment of two types of Long Period Fiber Grating (LPFG)-based sensors including a mobile liquid level sensor and a reflective sensor for the measurement of liquid level and fluid-flow velocity. Shewhart control charts were used to assess the liquid level sensing capacity and reliability of the mobile CO(2)-laser engraved LPFG sensor. There were ten groups of different liquid level experiment and each group underwent ten repeated wavelength shift measurements. The results showed that all measurands were within the control limits; thus, this mobile sensor was reliable and exhibited at least 100-cm liquid level measurement capacity. In addition, a reflective sensor consisting of five LPFGs in series with a reflective end has been developed to evaluate the liquid level and fluid-flow velocity. These five LPFGs were fabricated by the electrical arc discharge method and the reflective end was coated with silver by Tollen's test. After each liquid level experiment was performed five times, the average values of the resonance wavelength shifts for LPFG Nos. 1-5 were in the range of 1.35-9.14 nm. The experimental findings showed that the reflective sensor could be used to automatically monitor five fixed liquid levels. This reflective sensor also exhibited at least 100-cm liquid level measurement capacity. The mechanism of the fluid-flow velocity sensor was based on analyzing the relationship among the optical power, time, and the LPFG's length. There were two types of fluid-flow velocity measurements: inflow and drainage processes. The differences between the LPFG-based fluid-flow velocities and the measured average fluid-flow velocities were found in the range of 8.7-12.6%. For the first time to our knowledge, we have demonstrated the feasibility of liquid level and fluid-flow velocity sensing with a reflective LPFG-based sensor without modifying LPFGs or coating chemical compounds.


Computational Electrophysiology from a Single Molecular Dynamics Simulation and the Electrodiffusion Model.
The availability of high-resolution structures of ion channels opens the doors to reliable computations of electrophysiological properties, such as the dependence of ionic currents and selectivities on applied voltage. We develop two theoretical approaches for calculating these properties from molecular dynamics simulations at a single voltage, or even in the absence of voltage, combined with the electrodiffusion model in which ion motion in the channel is represented as one-dimensional diffusion in the potential of mean force exerted by other components of the system and the applied electric field. No knowledge of diffusivity or ion densities at other voltages is needed. Instead, in one approach, one-sided ion fluxes and density profiles are used to determine the free energy profile. In the other approach, committor probabilities for ions transported at the selected voltage are used for this purpose. Both approaches have been validated in an example of a simple ion channel formed by trichotoxin. The potentials of mean force calculated by way of the proposed approaches and obtained from traditional methods are in excellent agreement. Furthermore, the current-voltage dependence agrees very well with results obtained by way of computationally more demanding methods. We also have readily calculated the reversal potential, a computationally challenging electrophysiological property. The key assumptions of the electrodiffusion model, such as the independence of crossing events or the insensitivity of the potential of mean force to applied voltage, have been found to be satisfied. We also show that the voltage changes linearly in the hydrophobic core of the membrane and is constant elsewhere.


Navigating the Host Cell Response during Entry into Sites of Latent Cytomegalovirus Infection.
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection-where the virus establishes an infection in an absence of many gene products specific for lytic infection-these initial interactions are crucial events. In this review, we will discuss key host responses triggered by viral infection and how, in turn, the virus ameliorates the impact on the establishment of non-lytic infections of cells. We will focus on strategies to evade intrinsic antiviral and innate immune responses and consider their impact on viral infection. Finally, we will consider the hypothesis that the very early events upon viral infection are important for dictating the outcome of infection and consider the possibility that events that occur during entry into non-permissive cells are unique and thus contribute to the establishment of latency.


Application of double circular suturing technique (DCST) in the repair of large abdominal wall defects after resection of abdominal wall tumor.
The aim of this study was to investigate the clinical effects of repairing large defects using the double circular suturing technique (DCST) after resection of abdominal wall tumor. The clinical data of 62 patients (25 men, 37 women; average age 41.7±22.4 years) who underwent DCST between October 2010 and November 2018 for the repair of large abdominal wall defects with anti-adhesion underlay mesh after resection of abdominal wall tumor were retrospectively analyzed. The maximum diameter of abdominal wall defect after resection of abdominal wall tumor was 10.4±5.6 cm. The course of disease was 1-341 months, and the average was 32.4 months. Operative time, postoperative hospitalization time, perioperative complications, tumor recurrence in situ, incidence of postoperative chronic pain, and hernia were recorded. All 62 operations were completed successfully. The operative time was 73.2±31.4 minutes, and the mean postoperative hospitalization time was 9.6 days (range, 2-20 days). In total, 54 patients were followed up postoperatively for a median 6.7 years (range, 0.9-9.0 years). Partial splitting of incisions occurred in 2 patients, fat liquefaction of incisions occurred in 3 patients, and chronic pain occurred in 4 patients. No tumor in situ recurrence, hernia, or other complications were found in any cases in the follow-up. Tumor metastasis occurred in 9 patients with 6 of these patients dying of tumour progression. With simple operations, short procedure time, few complications, low tumor recurrence rate, and low incidence of postoperative chronic pain, application of DCST in the repair of large abdominal wall defects is effective after resection of abdominal wall tumor.


Fc Domain-Imprinted Stealth Nanogels Capable of Orientational Control of Immunoglobulin G Adsorbed In Vivo.
Regulation of nanomaterial-cell interaction is an important requisite for a variety of biomedical applications such as drug delivery systems and theranostics. Here, we demonstrate the regulation of nanomaterial-cell interaction using the oriented adsorption of intrinsic immunoglobulin G (IgG) on molecularly imprinted polymer nanogels (MIP-NGs) capable of recognizing the fragment crystallizable (Fc) domain of IgG. The unique domain recognition property resulted in the suppression of the immune response in Fc domain receptor-possessing macrophages and natural killer cells due to the regulation of protein corona based on the oriented adsorption of IgG. This resulted in the hindrance of the Fc domain, which is the trigger of an immune response. Furthermore, the acquisition of stealth capability was successfully demonstrated in vivo using intravital confocal laser scanning microscopy. The domain imprinting proposed in this study will provide a new strategy for creating nanomaterials capable of domain recognition-based oriented adsorption of intrinsic proteins in situ, thus regulating the protein corona formed on the nanomaterials. Thus, the unique Fc domain-recognition nanomaterial developed in our study can be used for various biomedical applications to target specific cells without triggering an immune response.


Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant Gram-negative bacilli.
SPR206 is a novel polymyxin analogue. Activity against clinical isolates is little documented. A collection of 200 MDR, carbapenem-resistant, tigecycline-resistant, colistin-resistant and non-MDR clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Stenotrophomonas maltophilia was obtained from 50 centres across China (2016-17). All isolates were derived from respiratory tract, urine and blood samples. Strains were purposely selected on the basis of phenotypes, genotypes and specimen origins. MICs of SPR206 and other antimicrobials were determined. SPR206 was active against all bacteria tested except colistin-resistant isolates. The MIC50/90 values of SPR206 for colistin-resistant strains were comparable to known polymyxins (16/128 versus 8/128 mg/L). SPR206 exhibited potent activity against colistin-susceptible OXA-producing A. baumannii (MIC50/90 = 0.064/0.125 mg/L), NDM-producing Enterobacteriaceae (MIC50/90 = 0.125/0.25 mg/L) and KPC-2-producing Enterobacteriaceae (MIC50/90 = 0.125/0.5 mg/L). In fact, SPR206 was the most potent agent tested, with 2- to 4-fold lower MICs than colistin and polymyxin B for A. baumannii, P. aeruginosa and Enterobacteriaceae. Additionally, MIC values of SPR206 (MIC50/90 = 0.064/0.125 mg/L) were 16- to 32-fold lower than those of tigecycline (MIC50/90 = 2/2 mg/L) for tigecycline-susceptible carbapenem-resistant A. baumannii. SPR206 showed good in vitro activity against MDR, tigecycline-resistant and non-MDR clinical isolates of Gram-negative pathogens. SPR206 also exhibited superior potency to colistin and polymyxin B, with 2- to 4-fold lower MIC50/90 values.


Novel peptides that inhibit the propagation of Newcastle disease virus.
A disulfide constrained random heptapeptide library displayed on filamentous bacteriophage M13 was applied to select specific ligands that interact with Newcastle disease virus (NDV). A fusion phage carrying the amino acid sequence TLTTKLY was selected from the panning procedure. An antibody competition assay showed that the selected phage was capable of competing with the polyclonal antibodies raised against NDV for binding sites on the virus. Determination of the binding affinity of this phage with NDV by an equilibrium binding assay in solution revealed two different dissociation constants, suggesting that there could be two distinct binding sites for the phage on NDV. Synthetic peptides with the sequence CTLTTKLYC, either in linear or cyclic conformations inhibited the binding of phage bearing the same sequence to NDV. These peptides also inhibited the hemolytic activity of the virus as well as its propagation in embryonated chicken eggs.


Concomitant overexpression of EGFR and CXCR4 is associated with worse prognosis in a new molecular subtype of non-small cell lung cancer.
Although the relationships between CXCR4 and EGFR expression and survival in non‑small cell lung cancer (NSCLC) have been studied independently, dual CXCR4/EGFR tumor status and its relationship with survival has not been previously investigated. In the present study, we examined the relationship between CXCR4 expression, EGFR expression and dual CXCR4/EGFR expression and survival in patients with NSCLC (n=125) using immunohistochemical techniques. Overall survival was estimated using Kaplan-Meier and Cox proportional hazards models adjusting for patient age, tumor stage and type of treatments. Patients with CXCR4-positive tumors were significantly associated with distant metastasis and tended to have poorer prognosis compared to patients with CXCR4-negative tumors (HR=2.172, 95% CI=1.229‑3.839). No significant association between EGFR expression and survival was found; however co-expression of CXCR4/EGFR was a significant prognostic factor of worse overall survival (HR=2.741, 95% CI=1.330‑5.741). Furthermore, we showed that EGF enhanced the expression of CXCR4 in NSCLC cells through the PI-3K pathway, and treatment of NSCLC cells with EGFR phosphorylation inhibitor, AG1478, resulted in downregulation of the expression of CXCR4. These results suggest an important interaction between CXCR4 and EGFR intra-cellular pathways that may activate signals of tumor progression and may provide a valid explanation for the poor overall survival rate of patients whose co-expression of CXCR4 and EGFR is detected in tissue sections. Based on EGFR and CXCR4 expression, new molecular subtypes of NSCLC established in the present study can be used for customization of NSCLC treatment. Our results also showed that EGFR and CXCR4 are potential therapeutic targets for NSCLC and that simultaneous inhibition of EGFR and CXCR4 in NSCLC patients with concomitant expression of both CXCR4 and EGFR may be an effective treatment strategy.


Short-term efficacy of superficial X-ray treatment for infantile maxillofacial hemangioma.
This study aimed to explore the short-term clinical efficacy and factors influencing low-dose superficial X-ray for treating infantile maxillofacial hemangioma. Retrospective analysis was conducted on 161 cases of infants with maxillofacial hemangioma treated with superficial X-ray in the Laser Center of Dermatology Department of Sichuan Provincial People's Hospital from January 2015 to December 2017. Clinical efficacy was analyzed by comparing the photos before and after treatment. Patients were further divided into groups according to different genders, age at the start of treatment, preterm birth or low birth weight, hemangioma site, longest diameter of hemangioma, and type of hemangioma to analyze whether differences existed in clinical efficacy and therapeutic dose between different groups. Twelve months after the end of treatment, the overall cure rate was 93.8%, and the significant efficiency was 97.5%. The clinical efficacy was related to the age of children at the beginning of treatment and the type of hemangioma (P<0.05). The clinical efficacy of children aged less than or equal to 12 months and superficial hemangioma group was better than that of children aged more than 12 months and deep subtype or mixed hemangioma group, respectively. Therapeutic doses associa-ted with hemangioma treatment with diameter, category, age (P<0.05), diameter greater than or equal to 4 cm hemangioma group, the mixed type or deep in the group, the children older than 12 months hemangioma group, respectively, the dia-meter is less than 4 cm hemangioma, superficial hemangioma group and age less than or equal to 12 months hemangioma total treatment group exposure dose is greater. Low-dose superficial X-ray is safe and effective for the treatment of infantile maxillofacial hemangioma. Age and type of hemangioma at the time of treatment are the factors influencing therapeutic dose and clinical efficacy.


Identification of Tse8 as a Type VI secretion system toxin from Pseudomonas aeruginosa that targets the bacterial transamidosome to inhibit protein synthesis in prey cells.
The Type VI secretion system (T6SS) is a bacterial nanomachine that delivers toxic effectors to kill competitors or subvert some of their key functions. Here, we use transposon directed insertion-site sequencing to identify T6SS toxins associated with the H1-T6SS, one of the three T6SS machines found in Pseudomonas aeruginosa. This approach identified several putative toxin-immunity pairs, including Tse8-Tsi8. Full characterization of this protein pair demonstrated that Tse8 is delivered by the VgrG1a spike complex into prey cells where it targets the transamidosome, a multiprotein complex involved in protein synthesis in bacteria that lack either one, or both, of the asparagine and glutamine transfer RNA synthases. Biochemical characterization of the interactions between Tse8 and the transamidosome components GatA, GatB and GatC suggests that the presence of Tse8 alters the fine-tuned stoichiometry of the transamidosome complex, and in vivo assays demonstrate that Tse8 limits the ability of prey cells to synthesize proteins. These data expand the range of cellular components targeted by the T6SS by identifying a T6SS toxin affecting protein synthesis and validate the use of a transposon directed insertion site sequencing-based global genomics approach to expand the repertoire of T6SS toxins in T6SS-encoding bacteria.


Genotyping by multiplexed sequencing (GMS): A customizable platform for genomic selection.
As genotyping technologies continue to evolve, so have their throughput and multiplexing capabilities. In this study, we demonstrate a new PCR-based genotyping technology that multiplexes thousands of single nucleotide polymorphism (SNP) markers with high-throughput capabilities in a simple protocol using a two-step PCR approach. The bioinformatic pipeline is user friendly and yields results that are intuitive to interpret. This method was tested on two recombinant inbred line (RIL) populations that had previous genotyping data from the Illumina Infinium assay for Triticum aestivum L. and the two data sets were found to be 100% in agreement. The genotyping by multiplexed sequencing (GMS) protocol multiplexes 1,656 wheat SNP markers, 207 syntenic barley SNP markers, and 49 known informative markers, which generate a possible 2,433 data points (including homoeoalleles and paralogs). This genotyping approach has the flexibility of being sequenced on either the Ion Torrent or Illumina next generation sequencing (NGS) platforms. Products are the result of direct sequencing and are therefore more reliable than scatter plot analysis which is the output of other genotyping methods such as the Illumina Infinium assay, komeptitive allele specific PCR and other like technologies.


Impact Wear of the Protective Cr3C2-Based HVOF-Sprayed Coatings.
High velocity oxygen-fuel (HVOF) prepared CrC-based hardmetal coatings are generally known for their superior wear, corrosion, and oxidation resistance. These properties make this coating attractive for application in industry. However, under some loading conditions and in aggressive environments, the most commonly used NiCr matrix is not sufficient. The study is focused on the evaluation of dynamic impact wear of the HVOF-sprayed Cr3C2-25%NiCr and Cr3C2-50%NiCrMoNb coatings. Both coatings were tested by an impact tester with a wide range of impact loads. The Wohler-like dependence was determined for both coatings' materials. It was shown that, due to the different microstructure and higher amount of tough matrix, the impact lifetime of the Cr3C2-50%NiCrMoNb coating was higher than the lifetime of the Cr3C2-25%NiCr coating. Differences in the behavior of the coatings were the most pronounced at high impact loads.


Working Memory Training in ADHD: Controlling for Engagement, Motivation, and Expectancy of Improvement (Pilot Study).
The aim of this study was to evaluate whether a shortened-length session of CogMed Working Memory Training (CWMT) would be a suitable active control group and evaluate study protocol to aid in design refinements for a larger randomized controlled trial (RCT). Thirty-eight post-secondary students diagnosed with ADHD were randomized into 25 sessions of standard (45 min/session) or shortened (15 min/session) CWMT, or into a waitlist control group. There was no significant difference in completion rate or training index score between the standard- and shortened-length groups indicating that both groups showed improvement and put forth good effort during training. Preliminary findings suggest that shorter training sessions may induce similar levels of engagement, motivation, and expectancy of improvement in participants. We conclude that a larger scale RCT that utilizes shortened-length training as an active control group is warranted, but that a few modifications to the study protocol will be required.


A Focused Multiple Reaction Monitoring (MRM) Quantitative Method for Bioactive Grapevine Stilbenes by Ultra-High-Performance Liquid Chromatography Coupled to Triple-Quadrupole Mass Spectrometry (UHPLC-QqQ).
Grapevine stilbenes are a family of polyphenols which derive from trans-resveratrol having antifungal and antimicrobial properties, thus being considered as phytoalexins. In addition to their diverse bioactive properties in animal models, they highlight a strong potential in human health maintenance and promotion. Due to this relevance, highly-specific qualitative and quantitative methods of analysis are necessary to accurately analyze stilbenes in different matrices derived from grapevine. Here, we developed a rapid, sensitive, and specific analysis method using ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC-QqQ) in MRM mode to detect and quantify five grapevine stilbenes, trans-resveratrol, trans-piceid, trans-piceatannol, trans-pterostilbene, and trans-ε-viniferin, whose interest in relation to human health is continuously growing. The method was optimized to minimize in-source fragmentation of piceid and to avoid co-elution of cis-piceid and trans-resveratrol, as both are detected with resveratrol transitions. The applicability of the developed method of stilbene analysis was tested successfully in different complex matrices including cellular extracts of Vitis vinifera cell cultures, reaction media of biotransformation assays, and red wine.


[Manuscript G. 108 inf. in the Ambrosiana library in Milan].
The manuscript G.180 inf. preserved in the Biblioteca Ambrosiana of Milan contains the Latin translations of three Hippocratic treatises (Prògnosticon, De aere, De septimanis) that were studied and published between the end of the XIXth and the beginning of the XXth century. But the second part of the manuscript is far more interesting and important. It contains four commentaries to Galen's four treatises: De sectis ad introducendos, Ars medica, De pulsibus ad tirones, Ad Glauconem de medendi methodo. The commentaries were composed in Ravenna between the 6th and the 7th century by "Agnellus iatrosophista" and were written by the physician Simplicius, surely one of Agnellus' pupils. But they aren't an original works by Agnellus: they are translations and combinations of original Greek commentaries compilated by Alexandrian scholars perhaps about the 6th century with Ammonius' and Olympiodorus' teaching method. At any rate, these commentaries testify the occurrence in Ravenna of a most active School of Medicine at the beginning of the Middle Ages. This school was a linear descendant of the School of Alexandria and transmitted classic medical culture first to the Beneventan medicine, and then, through the Beneventan medicine, to the early Schola Salenitana.


Effectiveness of Australia's Get Healthy Information and Coaching Service: maintenance of self-reported anthropometric and behavioural changes after program completion.
The Get Healthy Information and Coaching Service (GHS) is a population-wide telephone-based program aimed at assisting adults to implement lifestyle improvements. It is a relatively uncommon example of the translation of efficacious trials to up-scaled real-world application. GHS participants who completed the 6-month coaching program made significant initial improvements to their weight, waist circumference, Body Mass Index (BMI), physical activity and nutrition behaviours. This study examines the maintenance of anthropometric and behaviour change improvements 6-months after program completion. GHS coaching participants (n=1088) were recruited between February 2009 and June 2011. Participants were eligible if they completed the 6-month coaching program and had available data at 12-month follow-up (n=277). Weight, waist circumference, BMI, fruit and vegetable consumption and physical activity were collected at baseline and 6-months by GHS coaches and 12-months (6-months post program) by independent evaluators. Matched pair t-tests, mixed linear regression and logistic regression analyses were performed to assess maintenance of program effects. Improvements in weight (-2.9 kg, 95% CI: -3.6, -2.1), waist circumference (-5.4 cm, 95% CI: -6.7, -4.1), BMI (-1.1 units, 95% CI: -1.5, -0.8), and fruit (+0.3 serves per day, 95% CI: 0.2, 0.3) and vegetable (+0.5 serves per day 95% CI: 0.3, 0.6) consumption were observed from baseline to 12-months. Apart from vegetable consumption, there were no significant differences between 6-month and 12-month changes from baseline, indicating these risk factor improvements were maintained from the end of the coaching program. There were also improvements in the proportion of participants undertaking recommended levels of physical activity from baseline to 12-months (increase of 5.2%), however the improvements made at end of the coaching program were not maintained at the 6-month follow up. This study provides preliminary evidence that the GHS has potential to contribute to substantial improvements in the chronic disease risk factor profile of program completers and facilitates sustained maintenance six months after completing the coaching program.


Immigration and the direct long-term care workforce: implications for education and policy.
The escalating demand for trained direct long-term care (DLTC) workers, those individuals with the most sustained direct contact with vulnerable older adults in homes and facilities, is a consequence of our rapidly aging population. Research documents the present and projected shortages of DLTC workers, and developed nations are increasingly turning to immigrant women to fulfill these workforce needs. The authors identify international trends that influence the availability of these workers. Following a broad overview of the DLTC workforce, they turn to a specific examination of immigrants working in long-term care settings in the United States. The authors raise a number of questions about this changing workforce profile. They outline four ways that institutes of higher education can help improve the DLTC workforce in the United States and suggest that colleges and universities work in partnership with policy makers and the long-term care industry to this end.


[Variations in the use of hospital resources in treating patients with chronic obstructive pulmonary disease].
To analyze factors associated with the length of stay and pharmaceuticals expense for patients admitted with chronic obstructive pulmonary disease (COPD) and to evaluate whether treatment by different physicians means greater or less use of hospital resources. We retrospectively studied a cohort of 1033 COPD patients admitted to the Hospital de Mataró, Catalonia, Spain, during the years 1996 through 1998 in order to analyze factors associated with length of stay and pharmaceuticals use. We used the Minimum Basic Data Set, laboratory databases, and pharmacy single-dose database. We also analyzed the differences among patients treated by different physicians and developed multiple linear regression models to evaluate differences in treatment between one physician and another. The length of stay increased with patient age, the number of times admitted, the presence of atrial fibrillation or respiratory insufficiency, ventilatory alterations, chronicity, a forced expiratory volume in 1 second less than 50% of predicted, and treatment by certain physicians. Medication costs showed a similar pattern. Although the characteristics of patients treated by different physicians were quite homogeneous, the median length of stay varied from 9 to 11 days depending on the physician, while the median cost for medication varied from;43.62 to;54.39 (from $41.07 to $51.21). After removing the effects of several covariables by multiple regression analysis, an effect of physician persisted. Significant differences in length of hospital stay and consumption of pharmaceuticals are related to attending physician and continue to have an important effect after controlling for the differences in the severity of patient status.


How informal carers cope with terminal cancer.
This article reports selected findings from a qualitative study of informal carers. The study focused on people caring for relatives with terminal cancer and the findings reported here reflect how they cope with their relative's pain and medication. The author recommends that nurses involve carers in the decision making process to alleviate the stress carers experience and utilise their specialist knowledge of the patient.


Apoptosis in the iris and trabecular meshwork of medically treated and untreated primary open angle glaucoma patients.
To compare the trabecular meshwork (TM) and iris apoptosis of treated and untreated primary open angle glaucoma (POAG) patients. Eight treatment-naive, newly diagnosed (group 1) and 11 medicaly treated (group 2) patients with POAG were included in the study. Each patient underwent a limbus-based trabeculectomy. The TM and peripheral iris specimens were dissected out and were snap-frozen in liquid nitrogen and stored at -80°C until they were assayed. Apoptosis in each group was assesed by TUNEL method. The mean patient age was 60.6±5.8 years (53-68 years) vs 58.9±8.9 years (47-70 years) in group 1 and group 2 (P=0.859). The mean treatment time in group 2 was 22.2±7.3 months (12-34 months). Apoptotic indexes in TM and iris were significantly higher in POAG patients using medication (group 2) compared to treatment-naive POAG patients (group 1) (P=0.004, 0.015; respectively). Long term administration of topical antiglaucoma medications causes additional toxic effects on TM.


Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins.
Nicastrin is an integral component of the high molecular weight presenilin complexes that control proteolytic processing of the amyloid precursor protein and Notch. We report here that nicastrin is most probably a type 1 transmembrane glycoprotein that is expressed at moderate levels in the brain and in cultured neurons. Immunofluorescence studies demonstrate that nicastrin is localized in the endoplasmic reticulum, Golgi, and a discrete population of vesicles. Glycosidase analyses reveal that endogenous nicastrin undergoes a conventional, trafficking-dependent maturation process. However, when highly expressed in transfected cells, there is a disproportionate accumulation of the endo-beta-N-acetylglucosaminidase H-sensitive, immature form, with no significant increase in the levels of the fully mature species. Immunoprecipitation revealed that presenilin-1 interacts preferentially with mature nicastrin, suggesting that correct trafficking and co-localization of the presenilin complex components are essential for activity. These findings demonstrate that trafficking and post-translational modifications of nicastrin are tightly regulated processes that accompany the assembly of the active presenilin complexes that execute gamma-secretase cleavage. These results also underscore the caveat that simple overexpression of nicastrin in transfected cells may result in the accumulation of large amounts of the immature protein, which is apparently unable to assemble into the active complexes capable of processing amyloid precursor protein and Notch.


Diazepam Binding Inhibitor Promotes Stem Cell Expansion Controlling Environment-Dependent Neurogenesis.
Plasticity of adult neurogenesis supports adaptation to environmental changes. The identification of molecular mediators that signal these changes to neural progenitors in the niche has remained elusive. Here we report that diazepam binding inhibitor (DBI) is crucial in supporting an adaptive mechanism in response to changes in the environment. We provide evidence that DBI is expressed in stem cells in all neurogenic niches of the postnatal brain. Focusing on the hippocampal subgranular zone (SGZ) and employing multiple genetic manipulations in vivo, we demonstrate that DBI regulates the balance between preserving the stem cell pool and neurogenesis. Specifically, DBI dampens GABA activity in stem cells, thereby sustaining the proproliferative effect of physical exercise and enriched environment. Our data lend credence to the notion that the modulatory effect of DBI constitutes a general mechanism that regulates postnatal neurogenesis.


Retrograde Femoral Nailing Using Percutaneous Reduction Techniques.
Femoral shaft fractures are commonly treated with closed reduction and reamed intramedullary nailing. However, some reductions are difficult to obtain or maintain, especially in muscular or large patients. When closed methods fail to achieve reduction, percutaneous techniques are extremely useful. In addition, the use of either permanent or temporarily placed blocking implants offer a minimally invasive option for improving sagittal and coronal plane alignment. In the accompanying video, we describe our method of percutaneous reduction techniques in the setting of a comminuted femoral shaft fracture treated with a retrograde femoral intramedullary nail.


Circulating miR-21 and miR-155 as potential noninvasive biomarkers in Iranian Azeri patients with breast carcinoma.
Breast cancer (BC) is the most common cause of cancer-related mortality among women. Despite recent advances in diagnosis and prognosis of breast carcinomas, noninvasive biomarkers have been poorly identified. We evaluated the biomarker potential of miR-21 and miR-155 in tissue and plasma specimens of Iranian Azeri patients. Tumor specimens, paired nontumoral adjacent tissues, and matched plasma samples were collected from a number of thirty Iranian Azeri women with breast carcinoma. Plasma of healthy women was used as the control. The relative expression of miR-21 and miR-155 was measured by real-time polymerase chain reaction. Our data revealed that the expression levels of miR-21 and miR-155 in tumor tissues are significantly higher than paired nontumoral adjacent specimens (P < 0.05). Furthermore, receiver operating characteristic (ROC) curve analysis of samples showed the area under the ROC curve of 0.81 for miR-21 and area of 0.83 for miR-155. In addition, statistical analysis showed that miR-21 and miR-155 RNAs are significantly detected in the plasma of BC patients compared to healthy specimens (P < 0.05). Circulating miRNAs yielded area under the ROC curve of 0.99 for miR-21 and 0.92 for miR-155. Our data showed that miR-21 and miR-155 oncomiRs can be considered as noninvasive biomarkers for monitoring breast carcinomas. However, further investigations are needed to confirm the use of these noncoding RNAs in pathology.


Selective detection of trace Cr3+ in aqueous solution by using 5,5'-dithiobis (2-nitrobenzoic acid)-modified gold nanoparticles.
A simply prepared gold nanoparticle-based sensor, 5,5'-dithiobis (2-nitrobenzoic acid) (DTNBA)-modified gold nanoparticles, was prepared to explore the sensitive and selective detection of metal ions using a colorimetric technique. The selective detection of trace levels (93.6 ppb) Cr3+ in aqueous solution was achieved over 15 other metal ions. The functionalized gold nanoparticles became aggregated in solution in the presence of Cr3+ by an ion-templated chelation process, which caused an easily measurable change in the extinction spectrum of the particles and provided an inherently sensitive method for Cr3+ detection in aqueous solution.


Modelling the apparent mass of the standing human body under whole-body vibration training conditions.
Several studies have measured the vibration transmitted to and through the human body under vibration training conditions. However, no work has modelled the apparent mass of the human body under such conditions. In this work, a 2 degree-of-freedom model has been developed to predict the apparent mass of the standing human body under whole-body vibration training conditions. The parameters of the model were optimised using measured apparent mass of 12 subjects standing with different knee angle of 180°, 165°, 150° and 135°. Good agreement was found between the predicted and measured apparent mass with errors less than 3 kg in the median apparent mass magnitude and errors less than 6° in the apparent mass phase angle. The medians of the optimised parameters of the 12 individual apparent masses were close to the corresponding optimised parameters of the median apparent mass of the 12 subjects. Compared to standing with extended legs, bending the knees was found to affect mainly the parameters (i.e. stiffness and damping) of the model close to the source of vibration. Bending the knees decreased the mass of the model close to the source of vibration and increased the mass away from the source of vibration. Among the postures with bent knees, the change in the model parameters was generally not significant. The model can be used as a tool by manufacturers of whole-body vibration training machines to test the performance of the machines during the design stage and/or after production. This will decrease the number of experimentations with human subjects which guarantees consistency, repeatability, time-saving and safety.


A Carbon Cycle Model for the Social-Ecological Process in Coastal Wetland: A Case Study on Gouqi Island, East China.
Coastal wetlands offer many important ecosystem services both in natural and in social systems. How to simultaneously decrease the destructive effects flowing from human activities and maintaining the sustainability of regional wetland ecosystems are an important issue for coastal wetlands zones. We use carbon credits as the basis for regional sustainable developing policy-making. With the case of Gouqi Island, a typical coastal wetlands zone that locates in the East China Sea, a carbon cycle model was developed to illustrate the complex social-ecological processes. Carbon-related processes in natural ecosystem, primary industry, secondary industry, tertiary industry, and residents on the island were identified in the model. The model showed that 36780 tons of carbon is released to atmosphere with the form of CO2, and 51240 tons of carbon is captured by the ecosystem in 2014 and the three major resources of carbon emission are transportation and tourism development and seawater desalination. Based on the carbon-related processes and carbon balance, we proposed suggestions on the sustainable development strategy of Gouqi Island as coastal wetlands zone.


Observational retrospective study of vascular modulator changes during treatment in essential thrombocythemia.
Essential thrombocythemia (ET) patients are at risk of developing thrombotic events. Qualitative platelet (PLT) abnormalities and activation of endothelial cells (ECs) and PLTs are thought to be involved. Microparticles (MPs) can originate from PLTs (PMPs), ECs (EMPs), or red cells (RMPs). Previous studies have indicated that MPs contribute to ET pathophysiology. Endothelial modulators (eg, nitric oxide [NO], adrenomedullin [ADM], and endothelin-1 [ET-1]) are also involved in the pathophysiology of this condition. We hypothesized that treatments for reducing PLT count might also indirectly affect MP generation and endothelial activity by altering endothelial modulator production. The rationale of this study was that hydroxyurea (HU), a cytostatic drug largely used in ET, induces the production of a potent vasoactive agent NO in ECs. An observational retrospective study was designed to investigate the relationship between MPs, NO, ADM, and ET-1 in ET patients on treatment with HU, anagrelide (ANA), aspirin (ASA), and a group of patients before treatment. A total of 63 patients with ET diagnosis: 18 on HU + ASA, 15 on ANA + ASA, 19 on ASA only, and 11 untreated patients, and 18 healthy controls were included in this study. Blood samples were analyzed for MP (absolute total values) and functional markers (percentage values) by flow cytometry. PLT-derived MPs were studied using CD61, CD62P, CD36, and CD63, whereas endothelial-derived MPs were studied using CD105, CD62E, and CD144. Endothelial modulator markers (NO, ADM, and ET-1) were measured by ELISA. Total MP count was higher in the group treated with ANA + ASA (P < 0.01). MP markers modified in ET patients returned to levels of healthy controls following treatment, in particular, in patients on ANA treatment. NO and ADM values were higher in the HU group (P < 0.001). HU and ANA treatment also affected MP production in a cell origin-specific manner. HU and ANA, although acting via different pathways, have similar final effects. For instance, HU causes vasodilatation by increasing NO and ADM levels, whereas ANA impairs vasoconstriction by reducing ET-1. In conclusion, therapy with HU cytostatic drugs and ANA can reduce PLT count in ET, and also affect endothelial modulatory agents, with HU sustaining vasodilation and prothrombotic MP concentration, whereas ANA decreases vasoconstriction.


Expressions of Immune Negative Regulator FoxP3+Treg and PD-L1 Protein in the Immune Microenvironment of Cervical Lesion.
Objective To explore the expression patterns of immune negative regulator FoxP3+Treg and PD-L1 protein in cervical carcinoma and its precancerous lesions. Methods The expression patterns of FoxP3+Treg and PD-L1 protein in 45 cases of cervical lesions tissues of the cervix and 20 cases of normal cervix tissues by using immunohistochemistry (IHC). Results Compared with the normal cervix,the expressions of FoxP3+Treg (H=43.211,P=0.000) and PD-L1 protein (t=213.00,P=0.001) were significantly increased in cervical lesions. Compared with the low-grade squamous cell carcinoma,the invasiveness of FoxP3+Treg was increased in high-grade squamous cell carcinoma (H=28.307,P=0.000),along with increased expression of PD-L1 protein (t=239.000,P=0.028). The FoxP3+Treg expression was positively correlated with PD-L1 protein expression in abnormally differentiated cells (rs=0.364,P=0.003). Conclusion Along with the progression of cervical cancer,the FoxP3+Treg amount increases in the local microenvironment,along with enhanced PD-L1 protein expression in abnormally differentiated cells.


Design and monitoring of multi-arm multi-stage clinical trials.
Two-arm group sequential designs have been widely used for over 40 years, especially for studies with mortality endpoints. The natural generalization of such designs to trials with multiple treatment arms and a common control (MAMS designs) has, however, been implemented rarely. While the statistical methodology for this extension is clear, the main limitation has been an efficient way to perform the computations. Past efforts were hampered by algorithms that were computationally explosive. With the increasing interest in adaptive designs, platform designs, and other innovative designs that involve multiple comparisons over multiple stages, the importance of MAMS designs is growing rapidly. This article provides break-through algorithms that can compute MAMS boundaries rapidly thereby making such designs practical. For designs with efficacy-only boundaries the computational effort increases linearly with number of arms and number of stages. For designs with both efficacy and futility boundaries the computational effort doubles with successive increases in number of stages.


Mechanism of inhibition of DNA polymerases by 4'-epiadriamycin and 4'-O-tetrahydropyranyladriamycin.
4'-Epiadriamycin and 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), derivatives of adriamycin, strongly inhibited in vitro reactions of DNA polymerases alpha and beta from calf thymus by competing with activated DNA (template-primer). Preincubation of DNA polymerases with 4'-epiadriamycin or THP-adriamycin strongly inhibited the DNA polymerase, but the inhibition was reversed by adding excess amounts of template-primer. These results indicate that 4'-epiadriamycin and THP-adriamycin inhibit the in vitro reactions of DNA polymerases by direct interaction of the drugs with the enzymes as well as by impairing the template activity through intercalation into DNA, in agreement with results obtained for other anthracycline antitumor agents, daunomycin and adriamycin. The activity of DNA polymerase alpha may be more sensitive to both 4'-epiadriamycin (Ki, 9 microM) and THP-adriamycin (Ki, 5.5 microM) than that of DNA polymerase beta (Ki 30 microM for 4'-epiadriamycin and 22 microM for THP-adriamycin). DNA polymerase I from Escherichia coli was inhibited by these drugs in the same manner as DNA polymerase alpha. On the other hand, the inhibition of RNA polymerase from E. coli was more marked when the drug was preincubated with template DNA than with the enzyme.


Direct evidence for ferromagnetism of nanometer-scale palladium by contact with perovskite manganite.
Using a template method, we have synthesized hybrid Pd/La0.7Ca0.3-xSrxMnO3 (LCSMO) materials, which were evidenced by SEM, TEM, X-ray powder diffraction, and magnetization measurements. It was found that the Pd moment was induced by the rough LCSMO oxide, which was quantitatively analyzed. Our results provided direct evidence for ferromagnetism of nanosized Pd materials by contact with the perovskite manganite.


Molecular cloning and expression studies of two divergent alpha-tubulin genes in Neurospora crassa.
Three alpha-tubulin isoforms were previously detected in Neurospora crassa. We have cloned and analysed two alpha-tubulin cDNAs, Tub alpha A and Tub alpha B that encode polypeptides of 453 and 451 amino acids, respectively. The encoded amino acids exhibit an unusual divergence of 35%. This is the highest divergence ever observed between alpha-tubulins from the same species. The expression of the two genes is developmentally regulated. We did not detect any transcription of the Tub alpha A gene in dormant macroconidia and during the first 30 min of development even though the alpha-tub A protein is already present in the early stage of germination. In contrast, the Tub alpha B gene is continuously transcribed during the vegetative cycle and the expression profile of the protein follows the ones of its mRNA.


German community pastors' contact with palliative care patients and collaboration with health care professionals.
The current level of palliative care in Germany is unsatisfactory. Health care professionals view the psychosocial support of patients and families and the collaboration amongst the different care providers as the main deficiencies. In this context little is known about the viewpoints of community pastors who might have an important role in providing psychosocial and spiritual care for patients at home. In order to study their perspectives we performed 76 standardized telephone interviews with Protestant and Catholic pastors and examined how much contact pastors had with palliative care patients; their views of the collaboration with health care professionals; and how the pastors assessed their own skills in palliative care. Forty-one percent of respondents had no contact with any palliative care patients. The majority perceived collaboration with family doctors to be insufficient. The pastors assessed their own skills concerning palliative care predominantly as "satisfactory". Our findings suggest that community pastors' participation in the delivery of palliative care in Germany might be encouraged by specialized training and intensified contact with health care professionals.


[Mode of action of protamine sulfate on histamine secretion in the rat mast cells].
Protamine sulfate, known for a long time as a histamine releaser, was labeled with a fluorescent dye (FITC). This conjugate was shown to stain selectively the mast cell fraction of rat peritoneal cells. Within a few seconds, the protamine was found inside the cells. Although the cells had lost their histamine completely, no granules were found outside the cells. In the electron microscope, the protamine treated mast cells showed a loss of the electron density of their granules, a vacuolization, and other signs of histamine release. Evidence for a direct connection between the vacuoles and the extracellular fluid was gained by incubating mast cells in FITC-labeled human serum albumin followed by the addition of unlabeled protamine. After washing, the fluorescence was found to be located inside the cells, demonstrating an influx of the FITC-HSA under the influence of protamine. The protamine-induced release reaction is increased after addition of Ca2+, reduced by lowering the temperature, addition of 2-deoxyglucose, or cytochalasin B. Disodium cromoglycate also diminished the histamine release in a dose dependent manner. Protamine did not induce a loss of lactate dehydrogenase from the mast cells. The release reaction is mediated by the cell membrane, as shown by the releasing activity of insolubilized protamine. We conclude that the protamine-induced release is a non-cytotoxic reaction, fulfilling some criteria of the anaphylactic histamine release.


Systematic analysis of Zn2Cys6 transcription factors required for development and pathogenicity by high-throughput gene knockout in the rice blast fungus.
Because of great challenges and workload in deleting genes on a large scale, the functions of most genes in pathogenic fungi are still unclear. In this study, we developed a high-throughput gene knockout system using a novel yeast-Escherichia-Agrobacterium shuttle vector, pKO1B, in the rice blast fungus Magnaporthe oryzae. Using this method, we deleted 104 fungal-specific Zn(2)Cys(6) transcription factor (TF) genes in M. oryzae. We then analyzed the phenotypes of these mutants with regard to growth, asexual and infection-related development, pathogenesis, and 9 abiotic stresses. The resulting data provide new insights into how this rice pathogen of global significance regulates important traits in the infection cycle through Zn(2)Cys(6)TF genes. A large variation in biological functions of Zn(2)Cys(6)TF genes was observed under the conditions tested. Sixty-one of 104 Zn(2)Cys(6) TF genes were found to be required for fungal development. In-depth analysis of TF genes revealed that TF genes involved in pathogenicity frequently tend to function in multiple development stages, and disclosed many highly conserved but unidentified functional TF genes of importance in the fungal kingdom. We further found that the virulence-required TF genes GPF1 and CNF2 have similar regulation mechanisms in the gene expression involved in pathogenicity. These experimental validations clearly demonstrated the value of a high-throughput gene knockout system in understanding the biological functions of genes on a genome scale in fungi, and provided a solid foundation for elucidating the gene expression network that regulates the development and pathogenicity of M. oryzae.


Effect of temperature and oxidation rate on carbon-isotope fractionation during methane oxidation by landfill cover materials.
The quantification of methane oxidation is one of the major uncertainties in estimating CH4 emissions from landfills. Stable isotope methods provide a useful field approach for the quantification of methane oxidation in landfill cover soils. The approach relies upon the difference between the isotopic composition of oxidized gas at the location of interest and anaerobic zone CH4 and knowledge of alpha(ox), a term that describes the isotopic fractionation of the methanotrophic bacteria in their discrimination against (13)CH4. Natural variability in alpha(0x) in different landfill soils and the effect of temperature and other environmental factors on this parameter are not well defined. Therefore, standard determinations of alpha(ox), batch incubations of landfill cover soils with CH4, were conducted to determine alpha(ox) under a variety of conditions. When these results were combined with those of previous landfill incubation studies, the average alpha(ox) at 25 degrees C was 1.022 +/- 0.0015. alpha(ox) decreased with increasing temperature (-0.00039 alpha(ox) degrees C(-1)) overthe temperature range of 3-35 degrees C. alpha(ox) was found to be higher when determined after CH4-free storage and declined following CH4 pretreatment. alpha(ox) declined nonlinearly with increasing methane oxidation rate, Vmax.


alpha-tocopherol increases the intracellular glutathione level in HaCaT keratinocytes.
alpha-Tocopherol is a lipophilic vitamin that exhibits an antioxidative activity. The purpose of this study was to clarify the roles of alpha-tocopherol in the regulation of intracellular glutathione (GSH) levels in HaCaT keratinocytes. When HaCaT keratinocytes were cultivated with alpha-tocopherol for 24 h, the intracellular GSH was increased at every concentration of alpha-tocopherol tested. Furthermore, the HaCaT keratinocytes cultured with alpha-tocopherol at 50 microM for 24 h exhibited resistance against H2O2. However, a short exposure of HaCaT keratinocytes to alpha-tocopherol for 1 h did not influence either the GSH level or the resistance to H2O2. These findings suggest that GSH, which is inductively synthesized by alpha-tocopherol, effectively reduces exogenous oxidative stress. To evaluate the effect of alpha-tocopherol on the GSH level, BSO, which is a typical inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), was used. When BSO was added to HaCaT keratinocytes, no action of alpha-tocopherol on the GSH level was observed. On the other hand, alpha-tocopherol resulted in the up-regulation of gamma-GCS-HS (heavy subunit) mRNA. In addition, water soluble alpha-tocopherol derivatives (alpha-tocopherol phosphate and trolox) caused no changes in GSH level. From these results, it was concluded that alpha-tocopherol increases the intracellular GSH level of HaCaT keratinocytes through the up-regulation of gamma-GCS-HS mRNA.


Optimization of Iron Oxide Tracer Synthesis for Magnetic Particle Imaging.
The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based synthesis of multicore superparamagnetic iron oxide nanoparticles stabilized with dextran (MC-SPIONs). We also demonstrate the preparation of single core superparamagnetic iron oxide nanoparticles in organic media, subsequently coated with a poly(ethylene glycol) gallic acid polymer and phase transferred to water (SC-SPIONs). Our aim was to obtain long-term stable particles in aqueous media with high MPI performance. We found that the amplitude of the third harmonic measured by magnetic particle spectroscopy (MPS) at 10 mT is 2.3- and 5.8-fold higher than Resovist for the MC-SPIONs and SC-SPIONs, respectively, revealing excellent MPI potential as compared to other reported MPI tracer particle preparations. We show that the reconstructed MPI images of phantoms using optimized multicore and specifically single-core particles are superior to that of commercially available Resovist, which we utilize as a reference standard, as predicted by MPS.


Statin use and risk of kidney cancer: a meta-analysis of observational studies and randomized trials.
Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject. A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. A total of 12 (two randomized controlled trials, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results. The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.


[Preparation of a realistic calf model for obstetrical instruction].
Construction of a largely realistic and flexible calf-dummy for the instruction and practice of veterinary obstetrical procedures is described. The most important steps are presented in detail and illustrated by means of figures. The fundamental materials include: threaded rods, artificial metal joints, hard foam with a coating of soft foam rubber for neck and trunk, a flexible metal tube filled with silicone to imitate the vertebral column and silicone acetate injected into moulds to form the limb segments and the head. The natural skin, which had been specially tanned in order to retain its elasticity, was sewed over the flexible dummy. Adherence to the original proportions and a realistic replication of the limb joints ensured that the flexibility and movement of the dummy approaches that of an original calf.


Nuclear exclusion of TET1 is associated with loss of 5-hydroxymethylcytosine in IDH1 wild-type gliomas.
The recent identification of isocitrate dehydrogenase 1 (IDH1) gene mutations in gliomas stimulated various studies to explore the molecular consequences and the clinical implications of such alterations. The Cancer Genome Atlas Research Network showed evidence for a CpG island methylator phenotype in glioblastomas that was associated with IDH1 mutations. These alterations were associated with the production of the oncometabolite, 2-hydroxyglutarate, that inhibits oxygenases [ie, ten-eleven translocation (TET) enzymes involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC)]. We investigated 60 gliomas for 5hmC presence, 5-methylcytosine content, TET1 expression, and IDH1 mutation to gain insight into their relationships on a histological level. Of gliomas, 61% revealed no immunoreactivity for 5hmC, and no correlation was observed between IDH1 mutations and loss of 5hmC. Interestingly, expression of TET1 showed remarkable differences regarding overall protein levels and subcellular localization. We found a highly significant (P = 0.0007) correlation between IDH1 mutations and nuclear accumulation of TET1, but not with loss of 5hmC. Of 5hmC-negative gliomas, 70% showed either exclusive or dominant cytoplasmic expression, or no detectable TET1 protein (P = 0.0122). Our data suggest that the loss of 5hmC is a frequent event in gliomas, independent of IDH1 mutation, and may be influenced by the nuclear exclusion of TET1 from the nuclei of glioma cells.


A Discursive Review of Recent Development and Patents on Glycerosomes.
To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect. The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery. Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.


[Pharmaceutical properties of novel liposomes containing total alkaloids from seed of Strychnos nux-vomica].
To prepare the novel liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC) and soybean phosphatidylcholine (SPC) containing the total alkaloids from seed of Strychnos nux-vomica, and to compare the pharmaceutical properties of the novel liposomes with the corresponding HSPC or SPC liposomes. The total alkaloids were extracted from seeds of S. nux-vomica. and further purified. Novel liposomes containing the total alkaloids were prepared by ammonium sulfate transmembrane gradients and stealth liposome technique. Pharmaceutical properties such as encapsulation efficiency (EE), size, zeta potential and drug release profile of novel liposomes and corresponding HSPC or SPC liposomes were compared intensively. For novel liposomes, HSPC-SPC (1:3) was the best ratio which has the highest EE. At the drug/lipid weight ratio of 1:6, the EE of novel, SPC and HSPC liposomes were (73.6 +/- 2.9)%, (62.9 +/- 1.8)% and (54.7 +/- 1.0)% (n = 3), respectively. Compared with the corresponding SPC or HSPC liposomes, the size of novel liposomes was obviously decreased but the zeta potential was not different. The results of drug release showed that the novel liposomes were more stable than the SPC liposomes in the presence of rat plasma Taken together, high encapsulation efficiency improved stability in blood, and relative low price of phospholipids of the novel liposomes, indicate that the novel liposomes may act as promising carriers for anti-tumor traditional Chinese medicine.


Baculovirus nuclear import: open, nuclear pore complex (NPC) sesame.
Baculoviruses are one of the largest viruses that replicate in the nucleus of their host cells. During infection, the rod-shape, 250-nm long nucleocapsid delivers its genome into the nucleus. Electron microscopy evidence suggests that baculoviruses, specifically the Alphabaculoviruses (nucleopolyhedroviruses) and the Betabaculoviruses (granuloviruses), have evolved two very distinct modes for doing this. Here we review historical and current experimental results of baculovirus nuclear import studies, with an emphasis on electron microscopy studies employing the prototypical baculovirus Autographa californica multiple nucleopolyhedrovirus infecting cultured cells. We also discuss the implications of recent studies towards theories of nuclear transport mechanisms.


Effect of fibroblast growth factor and enamel matrix derivative treatment on root resorption after delayed replantation.
Periodontal ligament (PDL) healing and long term prognosis of replanted avulsed teeth should rely on several factors including length of extra-oral dry time and type of the storage medium. The status of periodontal ligament is critical for the healing of replanted teeth. Different substances have been used for root surface treatment to promote formation of PDL and increase the survival of avulsed teeth submitted to replantation. The purpose of this study was to assess the effect of recombinant basic fibroblast growth factor 2 (bFGF) and enamel matrix derivative (EMD) on root resorption after delayed replantation. 18 freshly extracted single-rooted incisor and premolar teeth were extracted from the beagle dogs and immersed in whole bovine milk for 45 and 60 min (n = 3 each). Following storage period, sockets washed and teeth were treated with bFGF and EMD and replanted into the sockets. After 8 weeks, dogs were sacrificed, specimens processed to 4-μm thick serial sections for histopathologic examination and morphometric assessments. Thus, the proportions of the roots that exhibited signs of surface resorption, inflammatory resorption, and replacement resorption, that is, ankylosis and normal PDL were noted. The percentage of root resorption was in the following order: EMD>milk>bFGF for 45 min and milk>EMD>bFGF for 60 min. For all groups, teeth stored 60 min showed significantly higher incidence of PDL resorption than those stored for 45 min (P < 0.01). The highest incidence of replacement resorption was observed in teeth treated with EMD for 60 min. After 8 weeks, the least resorption was found in bFGF-treated group (P < 0.01). The findings of this study suggest that use of bFGF favored the formation of new periodontal ligament; prevent ankylosis and resorption process following delayed replantation of teeth while EMD shows replacement resorption, which may turn to ankylosis.


Forty-Five Years of Civil Litigation Against Canadian Psychiatrists: An Empirical Pilot Study.
To extract the themes pertaining to prudent psychiatric practice from written court judgments in Canada. We searched the medical and legal literature for cases involving civil litigation against Canadian psychiatrist and reviewed all available written judgments. We completed a thematic analysis of the civil actions against psychiatrists as conveyed by those written court judgments. We classified the cases according to the disposal status and the essential lessons from the decisions on standard of care and practice by Canadian psychiatrists. Forty such cases were identified as involving psychiatrists over a 45-year period. A subgroup included those dealing with limitation periods and disclosure applications. Thirty of the 40 cases (75%) were decided in favour of the defendant psychiatrists, including 2 dismissed for running over the limitation period. The cases that actually went to trial suggest that documentation and obtaining second opinions are protective against claims of negligence. Inpatient cases resulting in successful litigation against psychiatrists involved fatal outcomes, but not all fatal outcomes led to successful litigation. The key lessons from these cases are the importance and relevance of regular best clinical practices, such as documentation, obtaining second opinions, following guidelines, and balancing competencies in the expert and manager or advocate roles. Incorporating these practices should allay concerns about litigation against psychiatrists.


Contributions of mass spectrometry to peptide and protein structure.
With the advent of recombinant deoxyribonucleic acid (DNA) technology which allows a wide range of manipulation of genes and their expression in cell lines other than the natural ones, many aspects of protein structure have become more important than ever. In addition to the determination of the amino acid sequence questions relating to homogeneity, the nature of post-translational modifications, the verification of the structure of a protein produced by a synthetically modified gene or the detection of a natural mutant are all questions that are more and more frequently asked and with the demand for more detail. Mass spectrometry has emerged as an important contributor to this field, particularly since the advent of fast atom bombardment (FAB) ionization, which makes it possible to ionize directly large polar molecules such as peptides and small proteins. As such, FAB mass spectrometry provides mainly molecular weight information which, in itself, often suffices to answer certain questions, particularly because the mass of many peptides can be determined directly from a single mass spectrum of a mixture. However, in order to obtain detailed structural information, such as the amino acid sequence, fragmentation has to be induced by collision processes and the product ions separated, preferably in the second mass spectrometer of a tandem system. This approach is particularly suited for the determination of the sequence of N-blocked peptides and the nature of the blocking group; the type and location of modified (i.e. phosphorylated, sulfated, glycosylated) amino acids; detection or verification of amino acid replacements; confirmation of the structure of synthetic peptides; and last but not least, the determination of the primary structure of proteins.


Blood Pressure and Penumbral Sustenance in Stroke from Large Vessel Occlusion.
The global burden of stroke remains high, and of the various subtypes of stroke, large vessel occlusions (LVOs) account for the largest proportion of stroke-related death and disability. Several randomized controlled trials in 2015 changed the landscape of stroke care worldwide, with endovascular thrombectomy (ET) now the standard of care for all eligible patients. With the proven success of this therapy, there is a renewed focus on penumbral sustenance. In this review, we describe the ischemic penumbra, collateral circulation, autoregulation, and imaging assessment of the penumbra. Blood pressure goals in acute stroke remain controversial, and we review the current data and suggest an approach for induced hypertension in the acute treatment of patients with LVOs. Finally, in addition to reperfusion and enhanced perfusion, efforts focused on developing therapeutic targets that afford neuroprotection and augment neural repair will gain increasing importance. ET has revolutionized stroke care, and future emphasis will be placed on promoting penumbral sustenance, which will increase patient eligibility for this highly effective therapy and reduce overall stroke-related death and disability.