Medicinal plants are a plentiful source of bioactive molecules with much structural diversity. In cancer treatment, molecules obtained from plants represent an attractive alternative to other treatments because several plant-derived compounds have exhibited lower toxicity and higher selectivity against cancer cells. In this review, we focus on the possible application of bioactive molecules obtained from plants against more primitive cell populations in cancers, cancer stem cells. Cancer stem cells are present in several kinds of tumors and are responsible for recurrences and metastases. Common anticancer drugs exhibit lower effectiveness against cancer stem cells because of their biological features. However, recently discovered natural phytometabolites exert cytotoxic effects on this rare population of cells in cancers. Therefore, this review presents the latest research on promising compounds from plants that can act as antitumor drugs and that mainly affect stem cell populations in cancers.
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Δευτέρα 13 Φεβρουαρίου 2017
Anti-Cancer Phytometabolites Targeting Cancer Stem Cells
Screening for breast cancer
Publication date: Available online 13 February 2017
Source:Seminars in Oncology
Author(s): Kimberly S. Peairs, Youngjee Choi, Rosalyn W. Stewart, Heather F. Sateia
This review will give a general overview of the impact of breast cancer, as well as breast cancer risk factors, identification of high-risk groups, screening modalities, and guidelines for screening average-risk and high-risk individuals, including a case discussion of the primary care provider's approach to screening.
http://ift.tt/2kFdlga
Phase I trial of low-dose interleukin 2 therapy in patients with Wiskott-Aldrich syndrome
Source:Clinical Immunology
Author(s): Soma Jyonouchi, Brenda Gwafila, Lavesh A. Gwalani, Maria Ahmad, Chistopher Moertel, Cecil Holbert, Ji Young Kim, Nathan Kobrinsky, Sumita Roy-Ghanta, Jordan S. Orange
BackgroundLow dose IL-2 can restore the function of T and NK cells from Wiskott-Aldrich (WAS) patients. However, the safety of in vivo IL-2 in WAS is unknown.ObjectivesA phase-I study to assess safety of low dose IL-2 in WAS.MethodsPatients received 5 daily subcutaneous IL-2 injections, every 2months, for three courses. A "3+3" dose escalation method was used.Results6 patients received the 0.5millionunits/m2/day dose without serious adverse events. However, 2 of 3 patients receiving the 1millionunits/m2/day dose developed thrombocytopenia requiring platelet transfusions. A statistically significant platelet increase occurred in patients receiving the 0.5millionunits/m2/day dose. A trend toward higher T, B and NK cell numbers and higher T regulatory cell percentages was observed.ConclusionWe have identified a safe IL-2 dose for WAS patients. Additional trials are indicated to study the efficacy of this immunostimulant as a therapy for WAS.
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Investigation on cellular uptake and pharmacodynamics of DOCK2-inhibitory peptides conjugated with cell-penetrating peptides
Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yusuke Adachi, Kotaro Sakamoto, Tadashi Umemoto, Yasunori Fukuda, Akiyoshi Tani, Taiji Asami
Protein–protein interaction between dedicator of cytokinesis 2 (DOCK2) and Ras-related C3 botulinum toxin substrate 1 (Rac1) is an attractive intracellular target for transplant rejection and inflammatory diseases. Recently, DOCK2-selective inhibitory peptides have been discovered, and conjugation with oligoarginine cell-penetrating peptide (CPP) improved inhibitory activity in a cell migration assay. Although a number of CPPs have been reported, oligoarginine was only one example introduced to the inhibitory peptides. In this study, we aimed to confirm the feasibility of CPP-conjugation approach for DOCK2-inhibitory peptides, and select preferable sequences as CPP moiety. First, we evaluated cell permeability of thirteen known CPPs and partial sequences of influenza A viral protein PB1-F2 using an internalization assay system based on luciferin–luciferase reaction, and then selected four CPPs with efficient cellular uptake. Among four conjugates of these CPPs and a DOCK2-inhibitory peptide, the inhibitory activity of a novel CPP, PB1-F2 fragment 5 (PF5), conjugate was comparable to oligoarginine conjugate and higher than that of the non-conjugated peptide. Finally, internalization assay revealed that oligoarginine and PF5 increased the cellular uptake of inhibitory peptides to the same extent. Hence, we demonstrated that CPP-conjugation approach is applicable to the development of novel anti-inflammatory drugs based on DOCK2 inhibition by investigating both cellular uptake and bioactivity.
Graphical abstract
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In vitro anticancer activity evaluation of new cationic platinum(II) complexes based on imidazole moiety
Publication date: Available online 14 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Isabella Rimoldi, Giorgio Facchetti, Giorgio Lucchini, Elisa Castiglioni, Silvia Marchianò, Nicola Ferri
The development and the synthesis of cationic platinum(II) complexes were realized and their cytotoxic activity was tested on triple negative breast cancer MDA-MB-231 cell line and in two cell lines poorly responsive to cisplatin (DLD-1 and MCF-7). The complex 2c resulted the most potent cytotoxic agent in MDA-MB-231 (IC50=61.9 µM) and more effective than cisplatin on both DLD-1 (IC50=57.4 µM) and MCF-7 (IC50=79.9 µM) cell lines. 2c showed different cellular uptake and pharmacodynamic properties than cisplatin, interfering with the progression of the M phase of the cell cycle. Thus, 2c represents a lead compound of a new class of cytotoxic agents with promising antitumor activity.
Graphical abstract
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Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3-and 4-(hetero)arylisoxazol-5-amine scaffolds
Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mikhail Krasavin, Mikhail Korsakov, Zhanna Zvonaryova, Evgenii Semyonychev, Tiziano Tuccinardi, Stanislav Kalinin, Muhammet Tanç, Claudiu T. Supuran
Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established and rationalized by in silico docking. These findings expand the structure-activity knowledge base for heterocycle-containing sulfonamide carbonic anhydrase inhibitors and further validate the power of direct electrophilic sulfochlorination as a means of introducing the pharmacophoric primary sulfonamide group into structurally diverse aromatic precursors.
Graphical abstract
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5-Ethynylarylnaphthalimides as Antitumor Agents: Synthesis and Biological Evaluation
Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Patricia Quintana-Espinoza, Pedro Martín-Acosta, Ángel Amesty, Patricia Martín-Rodríguez, Isabel Lorenzo-Castrillejo, Leandro Fernández-Pérez, Félix Machín, Ana Estévez-Braun
A set of 5-ethynylarylnaphthalimides was synthesized by Sonogashira cross-coupling reactions and evaluated for antiproliferative and antitopoisomerase II in vitro activities. Furthermore docking studies of these molecules as DNA-intercalators were carried out and the in vivo DNA-damaging activity was also determined with the model organism Saccharomyces cerevisiae. From the obtained results three naphthalimides 6, 13 and 14 showed strong topoisomerase II inhibitory activity. These three molecules also presented good docking scores as DNA-intercalators using a self-complementary oligodeoxynucleotide d(ATGCAT)2 as a model, and compounds 13 and 14 were among the most cytotoxic in the in vivo DNA-damaging activity.
Graphical abstract
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Synthesis and Biological Evaluation of Novel N3-substituted Dihydropyrimidine Derivatives as T-Type Calcium Channel Blockers and Their Efficacy as Analgesics in Mouse Models of Inflammatory Pain
Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mohamed Teleb, Fang-Xiong Zhang, Junting Huang, Vinicius M Gadotti, Ahmed M. Farghaly, Omaima M. AboulWafa, Gerald W. Zamponi, Hesham Fahmy
Low-voltage-activated calcium channels are important regulators of neurotransmission and membrane ion conductance. A plethora of intracellular events rely on their modulation. Accordingly, they are implicated in many disorders including epilepsy, Parkinson's disease, pain and other neurological diseases. Among different subfamilies, T-type calcium channels, and in particular the CaV3.2 isoform, were shown to be involved in nociceptive neurotransmission. The role of CaV3.2 in pain modulation was supported by demonstrating selective antisense oligonucleotide-mediated CaV3.2 knockdown, in vivo antinociceptive effects of T-type blockers, and pain attenuation in CaV3.2 knockout formalin-induced pain model. These Emerging investigations have provided new insights into targeting T-type calcium channels for pain management. Within this scope, various T-type calcium channel blockers have been developed such as mibefradil and ethosuximide. Although being active, most of these molecules interact with other receptors as well. This addresses the need for T- selectivity. Few selective T-type channel blockers of diverse chemical classes were developed such as ABT-639 and TTA-P2. Interestingly, R(-) efonidipine which is a dihydropyridine (DHP) showed T-channel selectivity. Systematic modification of 1,4-dihydropyridine scaffold introduced novel derivatives with 40 fold T-type selectivity over L-type calcium channels. Along these lines, substitution of the DHP core with various analogues favored T-selectivity and may serve as novel pharmacophores. Several dihydropyrimidine (DHPM) mimics were introduced by Squibb as potential candidates. As a continuation of this approach, the current study describes the synthesis of Novel N3 substituted DHPMs with structure similarities to the active DHPs. Different functional groups were introduced to the N3 position through a spacer to gain more information about activity and selectivity. Furthermore, the spacer aims at improving the metabolic stability of the molecules. Initial screening data by whole patch clamp technique showed a robust inhibition of Cav3.2 T-type channels by eleven compounds. Interestingly, four compounds of these were efficient selective T-type blockers. Based on selectivity and efficiency, two compounds were selected for in vivo evaluation in mouse models of inflammatory pain. Results showed effective attenuation of nociception and mechanical hypersensitivity.
Graphical abstract
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Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2
Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Nan Yang, Kamal Srivastava, Ying Song, Changda Liu, Sool Cho, Yujuan Chen, Xiu-Min Li
RationaleFood Allergy Herbal Formula 2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2.MethodsThe consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1mg of berberine or B-FAHF-2 containing anequivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined.ResultsBerberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the Cmax of B-FAHF-2 fed mice was 289.30±185.40ng/mL; whereas berberine alone showed very low bioavailability with Cmax value of 35.13±47.90ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%.ConclusionsB-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine.
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Peristomal psoriasis
Summary
Background
Psoriasis is a common skin condition, affecting 1.3–2.2% of the population. The prevalence of psoriasis has previously been reported as 11.2% in patients with Crohn disease (CD) and 5.7% in patients with ulcerative colitis.
Aim
To assess the prevalence of psoriasis around stoma sites and identify the most effective treatment.
Methods
A departmental database of all patients attendings stoma clinic was accessed between 1 May 2003 and 15 October 2015. Psoriasis response was determined by clinical resolution of psoriatic plaques in terms of erythema, induration, scaling and stoma bag adherence.
Results
Of 1665 patients, 78 (4.7%) had psoriasis affecting their abdominal stoma. In 8 patients (11.5%), a thicker hydrocolloid stoma bag barrier was sufficient to resolve the peristomal psoriasis. For 75 patients (96.2%), initial management was with nongreasy topical steroid scalp preparations and their usual barrier in the form of their stoma bag. Patients who did not respond to topical treatments initially or who experienced secondary failure (n = 16; 20.5%) received different systemic treatments [ciclosporin (n = 2), methotrexate (n = 2; 1 patient did not respond) or ultraviolet B narrowband phototherapy (n = 8; 2 nonresponders). One patient received infliximab and four patients received adalimumab for treatment of their CD, and their peristomal psoriasis also responded to these treatments. A further patient was prescribed adalimumab by the dermatology departmetn for the management of psoriasis vulgaris, with good response.
Conclusion
Peristomal psoriasis is common but potentially under-recognized. Selecting effective treatment that does not hinder bag appliance is crucial for effective management. Effective treatments include hydrocolloid dressings and topical corticosteroid regimens.
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Effectiveness of a commercial leptospiral vaccine on urinary shedding in naturally exposed sheep in New Zealand
Source:Vaccine, Volume 35, Issue 9
Author(s): Emilie Vallée, Anne L. Ridler, Cord Heuer, Julie M. Collins-Emerson, Jackie Benschop, Peter R. Wilson
L. borgpetersenii serovar Hardjo and L. interrogans serovar Pomona are endemic in New Zealand sheep. An effective vaccine and vaccination strategy would protect both humans and livestock.Four to 12 lambs were selected from each of eight farms (total=84, vaccinated group), while four to 16 lambs (total=98) served as unvaccinated controls. A commercial Hardjo/Pomona vaccine was given at 1–6 weeks of age, 5–11 weeks later and 33–67 weeks later on seven farms and at 18 weeks of age and 5 weeks later on the eighth farm. Vaccinates and controls were grazed together. Blood was regularly collected from the control group to assess flock exposure. Urine was collected from both groups 26–82 weeks after the second vaccination and tested by quantitative PCR.Seroprevalence in controls at the time of urine sampling ranged from 2.7 to 98.2% for Hardjo and from 0 to 54.1% for Pomona with seroconversion occurring 13 to 67 weeks after the second vaccination in all but one farm where exposure had happened by the time of vaccination. The shedding prevalence adjusted for clustering in farms was 45.1% [95% CI 17.6–72.7] (for an observed number of 50/98) in the control animals and 1.8% [95% CI 0.0–10.1] (for an observed number of 5/84) in the vaccinated animals. The vaccine was 100% effective on five farms where animals were vaccinated before 12 weeks of age and before natural exposure occurred, but the effectiveness was 80% [0–97] on one farm where the lambs were exposed before vaccination and 65% [9–87] to 80% [0–97] on one farm where the animals were fully vaccinated by 24 weeks of age. The overall vaccine effectiveness was 86.3% [63.6–94.8%] despite maternal antibodies in some flocks at first vaccination. Vaccination timing seemed to be crucial in achieving optimum reduction in shedding in urine in vaccinated sheep.
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On the need to wait 4 weeks between two live attenuated vaccines
Source:Vaccine, Volume 35, Issue 9
Author(s): Luiz Antonio Bastos Camacho
http://ift.tt/2kEOTMe
Editorial Board/Aims and Scope
Source:Vaccine, Volume 35, Issue 9
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Comparison of platform technologies for assaying antibody to Ebola virus
Source:Vaccine, Volume 35, Issue 9
Author(s): Dianna E. Wilkinson, Mark Page, Giada Mattiuzzo, Mark Hassall, Thomas Dougall, Peter Rigsby, Lindsay Stone, Philip Minor
BackgroundThe recent Ebola outbreak in West Africa led to the use of a variety of different platform technologies for assaying antibodies because of the difficulties of handling the live virus. The same types of method could be applied rapidly to other infections when they emerge. There is a need to compare quantitative results of different assays, which means that the assays must measure similar parameters and give comparable results.MethodsA collaborative study was carried out to establish an International Reference Reagent through WHO. Nine samples were sent to 16 laboratories and the results from 22 different assays compared to those obtained by neutralisation assays using the wild type virus.FindingsQuantitative correlation with the wild type neutralisation assays was very variable but generally poor, with only five of the twenty-two assays giving a correlation coefficient of 0.7 or greater; the five best assays included methods based on wild type and VSV pseudotype neutralisation and ELISA. They could be applicable to other rapidly emerging diseases. The remaining assays including neutralisation of lentiviral pseudotypes need further development.InterpretationThe assay platform should be chosen with care to ensure that it is fit for purpose. Many of the assays were not suitable for quantitation of antibody levels, a finding that is not surprising given the urgency with which they had to be implemented but some may be of generic value. Antibody titres in samples from a vaccine trial were comparable to those from convalescent patients or lower.FundingFunding was from the UK DoH and the Wellcome Tust.
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Placebo use in vaccine trials: Caution when using active vaccines as placebo
Source:Vaccine, Volume 35, Issue 9
Author(s): Stine Byberg, Christine Stabell Benn
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US medical students’ willingness to offer the HPV vaccine by vaccination status
Source:Vaccine, Volume 35, Issue 9
Author(s): Abbey B. Berenson, Jacqueline M. Hirth, Erika L. Fuchs
We surveyed third-year medical students to assess whether personal vaccination status was associated with willingness to recommend the human papillomavirus vaccine to patients. A total of 231 students completed an anonymous survey evaluating their knowledge, attitudes, and personal vaccine history. Of 122 female students, 81 (66.4%) reported initiating the vaccine, as did 16 of 109 males (14.7%). Females and students ⩽25years old were more likely to be vaccinated. Knowledge did not vary by vaccination status, but anticipated behaviors did. Vaccinated students reported greater willingness to vaccinate adolescents before 15–16years of age (92.1% vs. 78.6%, p=0.008) and discuss vaccination at any type of medical visit (100% vs. 89.7%, p<0.001). Our findings suggest that prior experiences with the HPV vaccine may influence a provider's future actions. Thus, interventions that increase awareness of this relationship as well as vaccination rates among health care students may be beneficial.
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Tick-borne encephalitis in China: A review of epidemiology and vaccines
Source:Vaccine, Volume 35, Issue 9
Author(s): Yi Xing, Heinz-Josef Schmitt, Adriano Arguedas, Junfeng Yang
Tick-borne encephalitis (TBE) has been shown to be endemic in northern and western China, including the three mountain areas in Heilongjiang, Jilin, Inner Mongolia, and Xinjiang. In addition, serology evidence shows that there is human infection in south-west provinces of China, including Xizang (Tibet) and Yunnan. TBE in China is caused by the Far Eastern TBE virus subtype and there is no biphasic course for disease presentation. The majority of TBE cases in China have occurred in people who were living or working in forests. TBE vaccines became available in China soon after the virus was identified in the country and they have been used for more than 60years to date, with different vaccine types used in different periods. Currently, an inactivated and purified whole-virus vaccine produced in a primary hamster kidney (PHK) cell line is used. Clinical trials have shown this vaccine to have higher immunogenicity and fewer adverse reactions than previous TBE vaccines. This paper provides a review on the epidemiology of TBE and the history of TBE vaccination in China.
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Integration of data from a safety net health care system into the Vaccine Safety Datalink
Source:Vaccine, Volume 35, Issue 9
Author(s): Simon J. Hambidge, Colleen Ross, Jo Ann Shoup, Kris Wain, Komal Narwaney, Kristin Breslin, Eric S. Weintraub, Michael M. McNeil
BackgroundIn 2013 the Institute of Medicine suggested that the Vaccine Safety DataLink (VSD) should broaden its population by including data of more patients from low income and racially and ethnically diverse backgrounds. In response, Kaiser Permanente Colorado (KPCO) partnered with Denver Health (DH), an integrated safety net health care system, to explore the integration of DH data.MethodsWe compared three different methods (reference date of September 1, 2013): "Empanelment" (any patient who has had a primary care visit in the past 18months), "Proxy-enrollment" (two health care visits in 3years separated by 90days), and "Enrollment" in a managed care plan. For each of these methods, we compared cohort size, vaccination rates, socio-demographic characteristics, and health care utilization.ResultsThe empaneled population at DH provided the best comparison to KPCO. DH's empaneled population was 111,330 (57,173 adults; 54,157 children), while KPCO had 436,290 empaneled patients (336,462 adults; 99,828 children). Vaccination rates in both health care systems for empaneled patients were comparable. Two year-old up-to-date coverage rates were 83.2% (KPCO) and 86.9% (DH); rates for adolescent Tdap and MCV4 were 85.5% (KPCO) and 90.6% (DH). There were significant differences in the two populations in age, gender, race, preferred language, and % Federal Poverty Level (FPL) (DH 70.7%<100% FPL; KPCO 17.4%), as well as in healthcare utilization – for example pediatric emergency department utilization was twice as high at DH.ConclusionsUsing a cohort of "empaneled" patients, it is possible to integrate data from a safety net health care system that does not have a uniform managed care population into the VSD, and to compare vaccination rates, socio-demographic characteristics, and health care utilization across the two systems. The KPCO-DH collaboration may serve as a model for incorporating data from a safety net healthcare system into the VSD.
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Recommendations and offers for adult influenza vaccination, 2011–2012 season, United States
Source:Vaccine, Volume 35, Issue 9
Author(s): Katharine M. Benedict, Tammy A. Santibanez, Carla L. Black, Helen Ding, Samuel B. Graitcer, Carolyn B. Bridges, Erin D. Kennedy
BackgroundProvider recommendations and offers for influenza vaccination improve adult influenza vaccination coverage. Analysis was performed to describe receipt of influenza vaccination recommendations and offers among adults who visited a healthcare provider (HCP) during the 2011–2012 influenza season and describe differences between those receiving and not receiving recommendations and offers for influenza vaccination. Associations between influenza vaccination and receipt of recommendations and offers were examined.MethodsRespondents to a random digit dial telephone survey who had visited a HCP since July 1, 2011 were asked if they had received a recommendation for influenza vaccination. Those receiving a recommendation were asked if they received an offer for vaccination. Participants were characterized by demographic and access to health care variables. Logistic regression was used to examine the relationships between participant characteristics and recommendation alone, between participant characteristics and recommendation and offer, and between influenza vaccination and recommendation and offer.ResultsOf those who reported visiting a HCP, 43.8% reported receiving a recommendation for influenza vaccination. Of those who reported receiving a recommendation, 76.6% reported receiving an offer for influenza vaccination. Persons with high-risk conditions and persons over 65 years were more likely to receive recommendations for influenza vaccination when compared to those without high-risk conditions and 18–49 year olds, respectively. Those reporting receipt of a recommendation and offer for influenza vaccination were 1.76 times more likely and those reporting receipt of a recommendation but no offer were 1.72 times more likely to report being vaccinated for influenza controlling for all patient characteristics.ConclusionsLess than half of respondents reported receipt of recommendations and offers of influenza vaccination during the 2011–2012 influenza season and disparities exist between groups. All healthcare providers seeing adults should recommend or offer influenza vaccination for all patients at every visit during the influenza season.
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Vaccine draining lymph nodes are a source of antigen-specific B cells
Source:Vaccine, Volume 35, Issue 9
Author(s): Stephanie C. Pero, Yu-Jing Sun, Girja S. Shukla, Chelsea L. Carman, Christopher C. Krag, Cory Teuscher, Dimitry N. Krementsov, David N. Krag
PurposeOur research is focused on using vaccine draining lymph nodes as a source of immune cells to better understand the immune response and to attempt to generate new anti-cancer reagents. Following a vaccine, harvesting the lymph node can only be done once. We endeavored to determine the range of times that B cells secreting anti-KLH antibodies were present in the node of KLH-vaccinated mice.ResultsFollowing vaccination the total number of mononuclear cells (MNCs) increased in the vaccine-draining lymph node (VDN). The percentage of MNCs that were B cells nearly doubled. B cells recovered from the node that secreted anti-KLH antibodies were evident by day 7. The number continued to increase and then slowly decreased over the observed time range to 28days after vaccination. The VDN, compared to the spleen, the bone marrow and the nonVDN, contained a higher percentage of B cells that secreted anti-KLH antibodies.ConclusionsAfter a vaccine, there is a multi-week window of time when an increasing number of B cells are present in a VDN that secrete anti-KLH antibodies. These results support using the VDN as a source for B cells that secrete anti-vaccine antibodies.
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Introduction of inactivated poliovirus vaccine leading into the polio eradication endgame strategic plan; Hangzhou, China, 2010–2014
Source:Vaccine, Volume 35, Issue 9
Author(s): Yan Liu, Jun Wang, Shijun Liu, Jian Du, Liang Wang, Wenwen Gu, Yuyang Xu, Shuyan Zuo, Erping Xu, Zhijie An
BackgroundChina's Expanded Program on Immunization (EPI) has provided 4 doses of oral poliovirus vaccine (OPV) since the 1970s. Inactivated poliovirus vaccine (IPV) became available in 2010 in Hangzhou as a private-sector, parent-chosen alternative to OPV. In 2015, WHO recommended that countries with all-OPV vaccination schedules introduce at least one dose of IPV, to mitigate risk associated with the withdrawal of type 2 OPV. We analyzed polio vaccine coverage and utilization in Hangzhou to determine patterns of IPV use and the occurrence of vaccine-associated paralytic polio (VAPP) in the various patterns identified.MethodsChildren born between 2010 and 2014 and registered in Hangzhou's Immunization Information System (HZIIS) were included. VAPP cases were detected through the acute flaccid paralysis surveillance system. We used descriptive epidemiological methods to determine IPV and OPV usage patterns and VAPP occurrence.ResultsHZIIS data from 566,894 children were analyzed. Coverage levels of polio vaccine were greater than 92% for each birth cohort. Percentages of children using OPV-only, IPV-only, and IPV/OPV sequential schedules were 70.57%, 27.01% and 2.41%, respectively. IPV-only schedule utilization increased by birth cohort regardless of geographical area or whether the child was locally-born. The highest use of an all-IPV schedule (79.85%) was among urban, locally-born children in the 2014 birth cohort. Five VAPP cases were identified during the study years; all cases occurred following the first polio vaccine dose, which was always OPV for the cases. Type 2 vaccine virus was isolated from 2 VAPP cases, and type 2 and type 3 vaccine virus was isolated from one VAPP case. The incidence of VAPP in the 2010–2014 birth cohorts was 3.76 per 1million doses of OPV.ConclusionChildren in Hangzhou had high polio vaccination coverage. IPV-only schedule use increased by year, and was highest in urban areas among locally-born children. All cases of VAPP were associated with the first dose of OPV.
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The rise and fall of pneumococcal serotypes carried in the PCV era
Source:Vaccine, Volume 35, Issue 9
Author(s): Vanessa T. Devine, David W. Cleary, Johanna M.C. Jefferies, Rebecca Anderson, Denise E. Morris, Andrew C. Tuck, Rebecca A. Gladstone, Grace O'Doherty, Priyasharmila Kuruparan, Stephen D. Bentley, Saul N. Faust, Stuart C. Clarke
Streptococcus pneumoniae is a major cause of meningitis, sepsis and pneumonia worldwide. Vaccination using pneumococcal conjugate vaccines (PCV) has therefore been part of the UK's childhood immunisation programme since 2006. Here we describe pneumococcal carriage rates in children under five years of age attending the paediatric department of a large UK hospital in response to vaccine implementation over seven winter seasons from 2006 to 2013. S. pneumoniae (n=696) were isolated from nasopharyngeal swabs (n=2267) collected during seven consecutive winters, October to March, 2006/7 to 2012/13. This includes the period immediately following the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2006 in addition to pre- and post-PCV13 introduction in 2010. We show a decrease in PCV13 vaccine serotypes (VT) in the three years following PCV13 vaccine implementation (2010/11 to 2012/13). Serotype 6A represented the only observed VT following PCV13 implementation with all others (including PCV7 serotypes) absent from carriage. Overall pneumococcal carriage, attributable to non-VT (NVT), was consistent across all sampling years with a mean of 31·1%. The ten most frequently isolated NVTs were 6C, 11A, 15B, 23B, 15A, 21, 22F, 35F, 23A and 15C. Fluctuations in the prevalence of each were however noted. Comparing prevalence at 2006/07 with 2012/13 only 15A was shown to have increased significantly (p value of 0·003) during the course of PCV implementation. These data support the increasing evidence that the primary effect of PCVs is due to population immunity by reducing or eliminating the carriage of invasive VT serotypes. With IPD being increasingly attributed to non-vaccine serotypes, surveillance of carriage data continues to act as an early warning system for vaccine design and public health policy that require continual data of both carried pneumococcal serotypes and IPD attributed serotype data.
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IL-17A and complement contribute to killing of pneumococci following immunization with a pneumococcal whole cell vaccine
Source:Vaccine, Volume 35, Issue 9
Author(s): Ivana B. Campos, Muriel Herd, Kristin L. Moffitt, Ying-Jie Lu, Michelle Darrieux, Richard Malley, Luciana C.C. Leite, Viviane M. Gonçalves
The pneumococcal whole cell vaccine (PWCV) has been investigated as an alternative to polysaccharide-based vaccines currently in use. It is a non-encapsulated killed vaccine preparation that induces non-capsular antibodies protecting mice against invasive pneumococcal disease (IPD) and reducing nasopharyngeal (NP) carriage via IL-17A activation of mouse phagocytes. Here, we show that PWCV induces antibody and IL-17A production to protect mice against challenge in a fatal aspiration-sepsis model after only one dose. We observed protection even with a boiled preparation, attesting to the stability and robustness of the vaccine. PWCV antibodies were shown to bind to different encapsulated strains, but complement deposition on the pneumococcal surface was observed only on serotype 3 strains; using flow cytometer methodology, variations in PWCV quality, as in the boiled vaccine, were detected. Moreover, anti-PWCV induces phagocytosis of different pneumococcal serotypes by murine peritoneal cells in the presence of complement or IL-17A. These findings suggest that complement and IL-17A may participate in the process of phagocytosis induced by PWCV antibodies. IL-17A can stimulate phagocytic cells to kill pneumococcus and this is enhanced in the presence of PWCV antibodies bound to the bacterial cell surface. Our results provide further support for the PWCV as a broad-range vaccine against all existing serotypes, potentially providing protection for humans against NP colonization and IPD. Additionally, we suggest complement deposition assay as a tool to detect subtle differences between PWCV lots.
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Control of infestations by Ixodes ricinus tick larvae in rabbits vaccinated with aquaporin recombinant antigens
Source:Vaccine, Volume 35, Issue 9
Author(s): Marinela Contreras, José de la Fuente
BackgroundTick-borne diseases greatly impact human and animal health worldwide, and vaccines are an environmentally friendly alternative to acaricides for their control. Recent results have suggested that aquaporin (AQP) water channels have a key function during tick feeding and development, and constitute good candidate antigens for the control of tick infestations.MethodsHere we describe the effect of vaccination with the Ixodes ricinus AQP1 (IrAQP) and a tick AQP conserved region (CoAQP) on I. ricinus tick larval mortality, feeding and molting.ResultsWe demonstrated that vaccination with IrAQP and CoAQP had an efficacy of 32% and 80%, respectively on the control of I. ricinus larvae by considering the cumulative effect on reducing tick survival and molting.ConclusionsThe effect of the AQP vaccines on larval survival and molting is essential to reduce tick infestations, and extended previous results on the effect of R. microplus AQP1 on the control of cattle tick infestations. These results supports that AQP, and particularly CoAQP, might be a candidate protective antigen for the control of different tick species.
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Three-dimensional growth of human endothelial cells in an automated cell culture experiment container during the SpaceX CRS-8 ISS space mission – The SPHEROIDS project
Source:Biomaterials, Volume 124
Author(s): Jessica Pietsch, Samuel Gass, Stefano Nebuloni, David Echegoyen, Stefan Riwaldt, Christin Baake, Johann Bauer, Thomas J. Corydon, Marcel Egli, Manfred Infanger, Daniela Grimm
Human endothelial cells (ECs) were sent to the International Space Station (ISS) to determine the impact of microgravity on the formation of three-dimensional structures. For this project, an automatic experiment unit (EU) was designed allowing cell culture in space. In order to enable a safe cell culture, cell nourishment and fixation after a pre-programmed timeframe, the materials used for construction of the EUs were tested in regard to their biocompatibility. These tests revealed a high biocompatibility for all parts of the EUs, which were in contact with the cells or the medium used. Most importantly, we found polyether ether ketones for surrounding the incubation chamber, which kept cellular viability above 80% and allowed the cells to adhere as long as they were exposed to normal gravity. After assembling the EU the ECs were cultured therein, where they showed good cell viability at least for 14 days. In addition, the functionality of the automatic medium exchange, and fixation procedures were confirmed. Two days before launch, the ECs were cultured in the EUs, which were afterwards mounted on the SpaceX CRS-8 rocket. 5 and 12 days after launch the cells were fixed. Subsequent analyses revealed a scaffold-free formation of spheroids in space.
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Killing colon cancer cells through PCD pathways by a novel hyaluronic acid-modified shell-core nanoparticle loaded with RIP3 in combination with chloroquine
Source:Biomaterials, Volume 124
Author(s): Xueyan Hou, Chengli Yang, Lijing Zhang, Tingting Hu, Dan Sun, Hua Cao, Fan Yang, Gang Guo, Changyang Gong, Xiaoning Zhang, Aiping Tong, Rui Li, Yu Zheng
Due to extensive apoptosis defects and multidrug resistance, there is great interest regarding non-apoptotic programmed cell death (PCD) pathways, such as lysosomal-mediated programmed cell death (LM-PCD), necroptosis and autophagy. Because there is an intricate effector network among these PCD pathways, it is expected that they may act synergistically in cancer therapy. In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy. Overexpressed-eGFP-RIP3 co-localized with the selective autophagy receptor p62. mRIP3 overexpression in combination with CQ markedly increased the inhibition rate relative to that observed in the CQ-treatment group. Several experiments, including Hoechst staining, transmission electron microscopy (TEM) observation, the high-mobility group box 1 (HMGB1) release assay, Annexin V/PI staining and immunoblotting of proteins included in PCD pathways, verified that mRIP3 overexpression in combination with CQ induced lysosomal membrane permeabilization (LMP) and necroptosis of cancer cells, leading to cancer cell death. For tumor-targeted delivery, hyaluronic acid (HA)-modified, lipid-coated PLGA nanoparticles loaded with mRIP3-pDNA were prepared and characterized using a particle sizer, differential scanning calorimetry (DSC) and TEM. The nanoparticles exhibited ideal biocompatibility and good tumor-targeting efficiency, and the tumor inhibition rate of HA-Lip-PEI-mRIP3-PLGA-NPs + CQ was 80.2% in the CT26 mouse model. In this study, we attempted to treat tumors by inducing several alternative PCD pathways to shed light on the combination therapy of alternative PCD inducers.
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Identification of differentially expressed proteins in retinoblastoma tumors using mass spectrometry-based comparative proteomic approach
Publication date: Available online 13 February 2017
Source:Journal of Proteomics
Author(s): Jasmine Naru, Ritu Aggarwal, Ashok Kumar Mohanty, Usha Singh, Deepak Bansal, Nandita Kakkar, Navneet Agnihotri
In India, retinoblastoma is among the top five childhood cancers. Children mostly present with extraocular extension and high risk features that results in unsatisfactory treatment and low survival rate. In addition, lack of potential therapeutic and prognostic targets is another challenge in the management of retinoblastoma. We studied comparative proteome of retinoblastoma patients (HPV positive and negative (n=4 each) and controls (n=4), in order to identify potential retinoblastoma-specific protein targets. 2D-DIGE coupled MALDI-TOF/TOF mass spectrometry identified 39 unique proteins. Highly deregulated proteins were GFAP,RBP3,APOA1,CRYAA,CRABP1,SAG and TF. Gene ontology (Panther 7.0) revealed majority of proteins to be associated with metabolic processes (26%) and catalytic activity (38%). 8 proteins were significantly upregulated in HPV positive vis-a-vis HPV negative cases. Patient group exhibited 12 upregulated and 18 downregulated proteins compared to controls. Pathway and network analysis (IPA software) revealed CTNNB1 as most significantly regulated signalling pathway in HPV positive than HPV negative retinoblastoma. The trends in transcriptional change of 9 genes were consistent with those at proteomic level. The Western blot analysis confirmed the expression pattern of RBP3,GFAP and CRABP1. We suggest GFAP,RBP3,CRABP1,CRYAAA,APOA1 and SAG as prospective targets that could further be explored as potential candidates in therapy and may further assist in studying the disease mechanism.SignificanceIn this study we evaluated tumor tissue specimens from retinoblastoma patients and identified 39 differentially regulated proteins compared to healthy retina. From these, we propose RBP3, CRABP1, GFAP, CRYAA, APOA1 and SAG as promising proteomic signatures that could further be explored as efficient prognostic and therapeutic targets in retinoblastoma. The present study is not only a contribution to the ongoing endeavour for the discovery of proteomic signatures in retinoblastoma, but, may also act as a starting point for future studies aimed at uncovering novel targets for further therapeutic interventions and improving patient outcomes.
Graphical abstract
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Assessment of operating room airflow using air particle counts and direct observation of door openings
Source:American Journal of Infection Control
Author(s): Jonathan Teter, Isabella Guajardo, Tamrah Al-Rammah, Gedge Rosson, Trish M. Perl, Michele Manahan
BackgroundThe role of the operating room (OR) environment has been thought to contribute to surgical site infection rates. The quality of OR air, disruption of airflow, and other factors may increase contamination risks. We measured air particulate counts (APCs) to determine if they increased in relation to traffic, door opening, and other common activities.MethodsDuring 1 week, we recorded APCs in 5-minute intervals and movement of health care workers. Trained observers recorded information about traffic, door openings, job title of the opener, and the reason for opening.ResultsAt least 1 OR door was open during 47% of all readings. There were 13.4 door openings per hour during cases. Door opening rates ranged from 0.19-0.28 per minute. During this time, a total of 660 air measurements were obtained. The mean APCs were 9,238 particles (95% confidence interval [CI], 5,494- 12,982) at baseline and 14,292 particles (95% CI, 12,382-16,201) during surgery. Overall APCs increased 13% when either door was opened (P < .15). Larger particles that correlated to bacterial size were elevated significantly (P < .001) on door opening.ConclusionsWe observed numerous instances of verbal communication and equipment movement. Improving efficiency of communication and equipment can aid in reduction of traffic. Further study is needed to examine links between microbiologic sampling, outcome data, and particulate matter to enable study of risk factors and effects of personnel movement.
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A randomized trial to determine the impact of a 5 moments for patient hand hygiene educational intervention on patient hand hygiene
Source:American Journal of Infection Control
Author(s): Herleen Rai, Shanina Knighton, Trina F. Zabarsky, Curtis J. Donskey
We conducted a randomized trial of a simple educational intervention encouraging patients to perform hand hygiene at 5 specific moments, including on entry of health care personnel into their room as a reminder of the importance of hand hygiene. The intervention resulted in a significant increase in patient hand hygiene.
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Atrial natriuretic peptide: a novel mediator for TGF-β1-induced epithelial-mesenchymal transition in 16HBE-14o and A549 cells
Source:Peptides
Author(s): Shuyuan Chu, Xiufeng Zhang, Yabing Sun, Yuanyuan Yu, Yaxi Liang, Ming Jiang, Jianwei Huang, Libing Ma
Atrial natriuretic peptide (ANP) is increasingly expressed on airway and inhibits pulmonary arterial remodeling. However, the role of ANP in remodeling of respiratory system is still unclear. The role of ANP on airway remodeling and the possible mechanism was explored in this study. Both human bronchial epithelial 16HBE-14o cells and alveolar epithelial A549 cells were stimulated by TGF-β1, ANP, cGMP inhibitor, PKG inhibitor, and cGMP analogue. The expressions of epithelial markers, mesenchymal markers, and Smad3 were assessed by quantitative real-time PCR and western blotting., Immunohistochemical staining was employed to assess Smad3 expression once it was silenced by siRNA in 16HBE-14o or A549 cells. Our results showed that the mRNA and protein expressions of E-Cadherin were decreased, whereas α-SMA expressions were increased after induction by TGF-β1 in 16HBE-14o and A549 cells. The E-Cadherin expressions were increased and α-SMA expressions were decreased after ANP stimulation. Inhibition of cGMP or PKG dexcrased E-Cadherin expression but increased α-SMA expression, which could be reversed by cGMP analogue. Moreover, the phosphorylated Smad3 expression was consistent with α-SMA expression. After smad3 was silenced, smad3 was mostly expressed in cytoplasm instead of nucleus as non-silenced cells during epithelial-mesenchymal transition (EMT). In conclusion, ANP inhibits TGF-β1-induced EMT in 16HBE-14o and A549 cells through cGMP/PKG signaling, by which it targets TGF-β1/Smad3 via attenuating phosphorylation of Smad3. These findings suggest the potential of ANP in the treatment on pulmonary diseases with airway remodeling.
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Scratch behavior of epoxy coating containing self-assembled zirconium phosphate smectic layers
Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Fan Lei, Marouen Hamdi, Peng Liu, Peng Li, Michael Mullins, Hongfeng Wang, Jiang Li, Ramanan Krishnamoorti, Shaoyun Guo, Hung-Jue Sue
A facile but efficient spray-coating method was recently developed to manufacture thin, flexible, and transparent epoxy films reinforced with well-exfoliated and highly-aligned α-zirconium phosphate (ZrP) nanoplatelets in smectic liquid crystalline order. Here, we investigate the scratch resistance of ZrP/epoxy nanocomposites prepared following the same spray-coating process. Comparison was made with neat epoxy coating to determine the impact of ZrP nanofillers. Tests were conducted with accordance to ASTM D7027/ISO 19252 scratch standard and scratch mechanisms were studied using different experimental tools. Results show that scratch resistance is considerably improved after introducing ZrP nanofillers to the epoxy coating. This was reflected by the delay in microcracking and plowing damages and the decrease of scratch coefficient of friction. This result is attributed to the significant role of exfoliated and aligned ZrP nanofillers in enhancing the mechanical properties of the epoxy matrix. The usefulness of the current study in developing new coating systems for high-performance applications is discussed.
Graphical abstract
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Adamantammonium as a novel functional group for anion exchange membranes with excellent comprehensive performances
Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Jinlei Wang, Ying Chen, Qi Wei, Shanzhong Yang, Huagao Fang, Haibing Wei, Yunsheng Ding
In the pursuit of alkali stable cation as functional group for anion exchange membranes (AEMs), a novel adamantammonium (AdA) cation, which replacing methyl group of conventional trimethylammonium by an adamantyl group, was synthesized and investigated. 1H NMR spectroscopy was employed to quantify the extent of decomposition and the results showed that > 99% adamantammonium remaining after 7 days immersion in 2 M NaOH (in D2O) at 80 °C. The AdA functionalized benzyl type poly(2,6-dimethyl phenylene oxide) polyelectrolytes, PPO-AdAs, were further prepared and characterized the AEM properties. Not only the chemical durability of these new PPO-AdA membranes, interestingly, but the conductivity and dimensional stability (water uptake and in-plane swelling) are superior to the benzylmethylammonium-benchmark PPO-based AEM (PPO-TMA). With the similar IEC values, the water uptake of PPO-AdA-41 sample is much lower than PPO-TMA-28, however, the conductivity of the former (15.7 mS cm-1, chloride conductivity at 50 °C) is higher than the latter (13.3 mS cm-1). Overall, the results of this study offer a base-stable cation, adamantammonium, and the corresponding adamantammonium-based AEMs for fuel cell applications with the advantages of chemical stability, enhanced conductivity and excellent dimensional stability as well as facial functionalization technique.
Graphical abstract
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A ‘grafting from’ approach to polymer nanorods for pH-triggered intracellular drug delivery
Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Théophile Pelras, Hien T.T. Duong, Byung J. Kim, Brian S. Hawkett, Markus Müllner
We report the use of the 'grafting from' approach to produce inherently rod-shaped polymer nanoparticles with triggered drug release. Cylindrical polymer brushes (CPBs) can be directly used to yield functional polymer nanorods for pH-sensitive drug release of doxorubicin (DOX). Water-soluble CPBs have been produced via a straightforward one-step grafting of vinyl benzaldehyde (VBA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) comonomers, in which the VBA distributed throughout the CPBs provides a cost-effective and simple functionality for the subsequent conjugation of DOX using imine chemistry. Atomic force microscopy (AFM) underlined the rod-like conformation of the CPBs prior and after drug conjugation. Fluorescence spectroscopy studies revealed faster drug release in acidic environments (pH 5.0) compared to physiological pH conditions (pH 7.4). Fluorescence lifetime imaging microscopy (FLIM) and in vitro cell studies further highlighted the intracellular DOX release from the CPB drug carriers within MCF-7 breast cancer cells.
Graphical abstract
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Segregated network formation of multiwalled carbon nanotubes in natural rubber through surfactant assisted latex compounding: A novel technique for multifunctional properties
Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Neena George, P.K. Bipinbal, Bhavya Bhadran, A. Mathiazhagan, Rani Joseph
In the present study Vulcastab VL (polyethylene oxide condensate) has been used as a non-ionic surfactant to get stable aqueous dispersions of multiwalled carbon nanotubes (MWCNTs). Sonication time and surfactant concentration were optimised by UV-vis spectroscopy and dynamic light scattering technique. Homogeneously dispersed surfactant coated individual MWCNTs in water were clearly evident from Transmission electron microscopy (TEM). Natural rubber –Multiwalled carbon nanotube (NR-MWCNT) nanocomposites were prepared by latex stage mixing. Instead of being randomly dispersed, MWCNTs were found to retain at the boundary of rubber particles resulting in a segregated network as evidenced from TEM. Addition of very small amount of MWCNT showed remarkable improvement in mechanical, thermal, electrical and barrier properties of NR. Segregated network of CNTs resulted in very low electrical percolation threshold (0.043 vol%) for the composite with enhanced dielectric properties.
Graphical abstract
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Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers
Background.
Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer-specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios.
Materials and MethodsWe identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next-generation sequencing-based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities.
Results.A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination.
Conclusions.Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. The Oncologist 2017;22:000–000
Implications for Practice: Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management.
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Fluorescent carbon dots and their sensing applications
Publication date: Available online 13 February 2017
Source:TrAC Trends in Analytical Chemistry
Author(s): Xiangcheng Sun, Yu Lei
Fluorescent carbon dots (CDs) are a new class of carbon nanomaterials and have demonstrated excellent optical properties, good biocompatibility, great aqueous solubility, low cost, simple synthesis, etc. Since their discovery, various synthesis methods using different precursors were developed, which were mainly classified as top-down and bottom-up approaches. CDs have presented many applications, and this review article mainly focuses on the development of CDs based fluorescent sensors in recent 5 years. The sensing mechanisms, senor design and sensing properties to various targets are summarized. A broad range of analytes including cations, anions, small molecules, macromolecules, cells and bacteria have been discussed. In addition, the challenges and future directions for CDs as sensing materials are also presented.
Graphical abstract
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Cholesterol Levels Should Play a More Important Role in Identifying Statin Recipients.
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Potential for Net Benefit Should Guide Preventive Therapy.
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Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.
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Mediterranean Approach to Improving High-Density Lipoprotein Function.
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Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).
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Is There a Role for Betrixaban to Prevent Stroke in Medically Ill Patients?.
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Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial.
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Neurological Injury and Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction.
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Stress-Activated Kinase Mitogen-Activated Kinase Kinase-7 Governs Epigenetics of Cardiac Repolarization for Arrhythmia Prevention.
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Cardiovascular and Ventilatory Consequences of Laparoscopic Surgery.
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Recommendations for the Implementation of Telehealth in Cardiovascular and Stroke Care: A Policy Statement From the American Heart Association.
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Is This Pacemaker Functioning Abnormally?.
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Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis.
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Letter by Messerli et al Regarding Article, "The Implications of Blood Pressure Measurement Methods on Treatment Targets for Blood Pressure".
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Response by Bakris to Letter Regarding Article, "The Implications of Blood Pressure Measurement Methods on Treatment Targets for Blood Pressure".
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Correction to: Use of Sodium Glucose Cotransporter 2 Inhibitors in the Hands of Cardiologists: With Great Power Comes Great Responsibility.
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When and Where Learning is Taking Place: Multisynaptic Changes in Strength During Different Behaviors Related to the Acquisition of an Operant Conditioning Task by Behaving Rats
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Although it is generally assumed that brain circuits are modified by new experiences, the question of which changes in synaptic efficacy take place in cortical and subcortical circuits across the learning process remains unanswered. Rats were trained in the acquisition of an operant conditioning in a Skinner box provided with light beams to detect animals' approaches to lever and feeder. Behaviors such as pressing the lever, eating, exploring, and grooming were also recorded. Animals were chronically implanted with stimulating and recording electrodes in hippocampal, prefrontal, and subcortical sites relevant to the task. Field synaptic potentials were evoked during the performance of the above-mentioned behaviors and before, during, and after the acquisition process. Afferent pathways to the hippocampus and the intrinsic hippocampal circuit were slightly modified in synaptic strength during the performance of those behaviors. In contrast, afferent and efferent circuits of the medial prefrontal cortex were significantly modified in synaptic strength across training sessions, mostly at the moment of the largest change in the learning curve. Performance of behaviors nondirectly related to the acquisition process (exploring, grooming) also evoked changes in synaptic strength across training. This study helps to understand when and where learning is being engraved in the brain.</span>
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High-efficiency breeding of early-maturing rice cultivars via CRISPR/Cas9-mediated genome editing
Source:Journal of Genetics and Genomics
Author(s): Xiufeng Li, Wenjia Zhou, Yuekun Ren, Xiaojie Tian, Tianxiao Lv, Zhenyu Wang, Jun Fang, Chengcai Chu, Jie Yang, Qingyun Bu
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The diagnostic accuracy of a laser fluorescence device and digital radiography in detecting approximal caries lesions in posterior permanent teeth: an in vivo study
Abstract
The aim of this in vivo study was to test the diagnostic accuracy of a pen-type laser fluorescence (LFpen) device in detecting approximal caries lesions, in posterior permanent teeth, at the cavitation and non-cavitation thresholds, and compare it with that of digital bitewing radiography. Thirty patients (aged 18–37), who attended the Faculty of Dentistry at Damascus University for a dental examination, were consecutively screened. Ninety approximal surfaces of posterior permanent teeth without frank cavitations, enamel hypoplasia or restorations were selected and examined using the LFpen (DIAGNOdent pen) and digital bitewing radiography. The reference standard was the visual-tactile inspection, after performing temporary tooth separation, using orthodontic rubber rings, placed for 7 days. The status of included approximal surfaces was recorded as intact/sound, with white/brown spots or cavitated. One trained examiner performed all examinations. There were statistically significant differences in LFpen readings between the three types of approximal surface status (P < 0.001). The optimal cut-off values for detecting approximal caries lesions in posterior permanent teeth were >16 and 8 at the cavitation and non-cavitation thresholds respectively. The sensitivity, specificity and accuracy (measured by the area under the receiver-operating characteristic curve) were 100, 85 and 95 and 92, 90 and 95% at the cavitation and non-cavitation thresholds respectively. The intra-class correlation coefficient for intra-examiner reliability was 0.95. The diagnostic accuracy of the LFpen was significantly higher than that of digital bitewing radiography (P < 0.001). The LFpen's diagnostic performance was accurate and significantly better than digital bitewing radiography in detecting approximal caries lesions, in posterior permanent teeth.
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Role of precursors on the photophysical properties of carbon nitride and its application for antibiotic degradation
Abstract
In this paper, we provide a comprehensive evaluation of graphitic carbon nitride (C3N4) powders derived from the four different precursors melamine, cyanamide, thiourea, and urea for the photocatalytic degradation of tetracycline (TC) antibiotic under sunlight irradiation. The powders were synthesized by employing the conventional thermal decomposition method. The synthesized powders were examined using different characterization tools for evaluating the photophysical properties. The degradation profile revealed that urea-derived C3N4 showed the highest activity while melamine-derived C3N4 showed the least activity. The TC degradation efficiency of the photocatalyst was found to be influenced more by the surface area values despite extended absorption by melamine in the visible light region. Stability tests on urea-derived C3N4 and others were checked by four runs of TC degradation under sunlight irradiation. The synthesized C3N4 powders also confirmed the dominance of urea-derived powders for cyclic stability.
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Soil properties and microbial ecology of a paddy field after repeated applications of domestic and industrial sewage sludges
Abstract
The effects of repeated application of two types of sewage sludge, domestic and industrial (petrochemical, PSS) sludges, into paddy fields over a 5-year period on the soil properties and microbial ecology were studied and compared with conventional NPK fertilizer application. Soil organic matter and total nitrogen contents were significantly higher in the two sludge treatments than that in fertilized plots after 5 years. Soil concentrations of potentially toxic metals were low after 5 years of both sludge treatments, but the polycyclic aromatic hydrocarbons (PAHs) showed differences between the two sludge types. Concentrations of high-molecular-weight PAHs were significantly higher (p < 0.05) in the petrochemical sludge treatment than the domestic sludge treatment or the fertilizer control, although the total concentrations of 16 types of PAH in the petrochemical sludge treatment were only slightly higher than in the domestic sludge treatment and the control. The biological toxicity of soil dimethyl sulfoxide extracts from the petrochemical sludge treatment was also significantly higher (p < 0.05) than those from the fertilizer control and the domestic sludge treatment when evaluated using Photobacterium phosphoreum T3. Both types of sewage sludge increased soil microbial activity, but only the petrochemical sludge led to enrichment with specific PAH degraders such as Mycobacterium, Nocardioides, and Sphingomonas.
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Determining the best recipient vessel site for autologous microsurgical breast reconstruction with DIEP flaps: an anatomical study
The deep inferior epigastric perforators (DIEP) flap is a reliable and reproducible technique for autologous microsurgical breast reconstruction. Several recipient vessels sites for microvascular anastomosis have been described: the internal thoracic vessels, the thoracodorsal vessels and the circumflex scapular vessels. Nonetheless, the choice of the recipient site depends mainly on individual operator's experience and preferences, and currently the best recipient vessel site is still debated. The aim of this anatomical observational study was to determine whether anatomy could address this dilemma by determining the best vessel diameter to match the donor with these 3 recipient sites.
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Effect of soil contamination with fluorine on the yield and content of nitrogen forms in the biomass of crops
Abstract
The research was based on a pot experiment, in which the response of eight species of crops to soil contamination with fluorine was investigated. In parallel, some inactivating substances were tested in terms of their potential use for the neutralization of the harmful influence of fluorine on plants. The response of crops to soil contamination with fluorine was assessed according to the volume of biomass produced by aerial organs and roots as well as their content of N-total, N-protein, and N-NO3−. The following crops were tested: maize, yellow lupine, winter oilseed rape, spring triticale, narrow-leaf lupine, black radish, phacelia, and lucerne. In most cases, soil pollution with fluorine stimulated the volume of biomass produced by the plants. The exceptions included grain and straw of spring triticale, maize roots, and aerial parts of lucerne, where the volume of harvested biomass was smaller in treatments with fluorine-polluted soil. Among the eight plant species, lucerne was most sensitive to the pollution despite smaller doses of fluorine in treatments with this plant. The other species were more tolerant to elevated concentrations of fluorine in soil. In most of the tested plants, the analyzed organs contained more total nitrogen, especially aerial organs and roots of black radish, grain and straw of spring triticale, and aerial biomass of lucerne. A decrease in the total nitrogen content due to soil contamination with fluorine was detected only in the aerial mass of yellow lupine. With respect to protein nitrogen, its increase in response to fluorine as a soil pollutant was found in grain of spring triticale and roots of black radish, whereas the aerial biomass of winter oilseed rape contained less of this nutrient. Among the analyzed neutralizing substances, lime most effectively alleviated the negative effect of soil pollution with fluorine. The second most effective substance was loam, while charcoal was the least effective in this respect. Our results showed the effect of soil contamination with fluorine on the yield and chemical composition of fluorine depended on the species and organ of a tested plant, on the rate of the xenobotic element and on the substance added to soil in order to neutralize fluorine.
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Carbonation of gypsum from wet flue gas desulfurization process: experiments and modeling
Abstract
In this paper, waste gypsum from wet flue gas desulfurization (WFGD) mixed with NH3·H2O was applied for CO2 absorption in the solid-liquid-gas phase system. The effects of operation temperature, CO2 flow rates, and ammonia-to-gypsum ratio on carbonation process were discussed. Meanwhile, a model for CO2 absorption in the suspension of WFGD gypsum and ammonia was established. The results indicate that higher temperature favors the reaction, and WFGD gypsum conversion can be achieved above 90% even at lower ammonia-to-gypsum ratio, while CO2 conversion reaches 90% and ammonia utilization is up to 83.69%. The model fits well with the experimental results at various CO2 flow rates and predicts the concentration distribution of the main species, including CO2 absorbed, NH2COO−, and HCO3−.
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Determination of glyphosate in surface water with high organic matter content
Abstract
In this paper, we investigate the sample preparation and analysis process in order to achieve adequate results for surface water collected from rivers that flow through swamps and are consequently rich in organic matter. We show that matrix effects in glyphosate determination can be reduced by optimizing sample volume, liquid chromatography (LC) mobile phase buffer concentration and pH as well as gradient speed. Also, aspects of derivatization procedure (borate buffer concentration, fluorenylmethyloxycarbonyl chloride concentration) and their influence on accuracy are considered in detail. We encountered a cross-talk effect in the mass spectra, interfering with quantization during analysis, which was removed by optimizing MS parameters. As a result it was demonstrated that isotope-labelled internal standard with just one 13C atom is sufficient for the analysis.
All these aspects were found to strongly impact the accuracy of the glyphosate determination but have received little or no attention in earlier works. We propose a reliable solid phase extraction and LC/ESI/MS/MS method for determination of glyphosate in organic-rich waters and demonstrate that LoD can be decreased by about two times using an ESI nebulizer with a modified design.
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Functional Dental Restorative Materials That Hinder Oral Biofilm
Abstract
Purpose of Review
This review highlighted the state of the art regarding functional materials that have been used to hinder oral biofilm, focused on the materials used over the last 3 years to achieve an antimicrobial effect, considering the effects of its modification on the physical properties.
Recent Findings
Because dental restorations have failures and the main cause was found to be the presence of secondary caries, the recent studies in this field are focused on development of functional dental materials with the ability to hinder oral biofilm. Therefore, composite resins, glass ionomer cement, and dental adhesive systems have been modified with different functional materials to obtain the antibiofilm properties. For this purpose, several antimicrobial materials have been used, such as inorganic fillers nanoparticles, bioactive glass, functional monomers, and chlorhexidine.
Summary
The ability of materials to hinder biofilm-dependent diseases depends on the amount of the antimicrobial materials, size, physical and chemical properties. In the last years, studies have demonstrated great results in the use of materials aiming to decrease or control oral biofilm formation; however, some authors indicate that research of bacterial effects on these materials are still needed.
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Risk factors for hospitalization of children with congenital adrenal hyperplasia
Abstract
Background and Objectives
Patients with congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency are prone to potentially life-threatening adrenal crises. We tried to identify risk factors for post-diagnosis hospitalization for children with the salt wasting form of CAH.
Methods
We reviewed medical records of all children who presented to Children's Medical Center Dallas from 1999 to 2013 with congenital adrenal hyperplasia (ICD-9 code 255.2).
Results
522 unique patients were coded for ICD-9 code of 255.2 (CAH) from 1999-2013; 155 patients had salt- wasting disease. 55 patients were hospitalized a total of 105 times. Patients who were hospitalized were more likely to have non-commercial insurance (RR=1.8; 95% CI [1.1-2.8]; p=0.02); this included 5 patients hospitalized a total of 37 times. Children younger than 2 years (RR=3.3 [2.2-4.8]; p<0.0001) were more likely to be hospitalized. In a nested case control analysis, the risk of hospitalization was correlated with daily fludrocortisone dose (p≤0.0001) but not hydrocortisone dose; no outpatient laboratory test predicted hospitalization. Gastroenteritis was the most frequent admitting diagnosis.
Conclusions
Younger children may be at greater risk of hospitalization owing to increased susceptibility to viral infections and decreased ability to withstand stress and dehydration. A minority of patients with non-commercial insurance may have higher risk owing to social barriers that interfere with treatment compliance. Those requiring higher daily fludrocortisone dosages likely have inherently more severe disease leading to higher rates of hospitalization.
This article is protected by copyright. All rights reserved.
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Mucosal melanoma of the head and neck
Publication date: Available online 13 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations.One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery. Many new treatment options in the last years, in particular targeted therapies (i.e. inhibitors of c-KIT, NRAS/MEK or BRAF) and immunotherapies (anti CTLA-4 and anti PD-1/PD-L1 antibodies), have changed the history of cutaneous melanoma. Despite the different biology, mucosal melanoma is currently treated in the same way as cutaneous melanoma; however, patients with mucosal melanoma were excluded from the majority of recent clinical trials. Recent molecular findings offer new hope for the development of more effective systemic therapy.
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Kisspeptin-10 inhibits proliferation and regulates lipolysis and lipogenesis processes in 3T3-L1 cells and isolated rat adipocytes
Abstract
Introduction
Kisspeptin, which is encoded by the KISS1 gene and acts via GPR54, plays a role in the regulation of reproductive functions. Expression of KISS1 and GRPR54 has been found in peripheral tissues, including adipose tissue, and was shown to be influenced by metabolic status.
Purpose
We hypothesized that kisspeptin could be involved in regulation of lipid metabolism in the mouse 3T3-L1 cell line and in isolated rat adipocytes.
Methods
First, we characterized expression profiles of KISS1 and GPR54 mRNA and proteins in adipose cells isolated from male rats. Secondly, we studied the effects of kisspeptin-10 on cell proliferation and survival in 3T3-L1 cells. Thirdly, we assessed the rapid action of kisspeptin-10 on lipid metabolism and glucose uptake using 3T3-L1 cells and rat primary adipocytes. Finally, we examined the effects of kisspeptin-10 on the secretion of leptin and adiponectin in rat adipocytes.
Results
We have found that: (1) KISS1 and GPR54 were expressed in mouse 3T3-L1 cells and isolated rat adipocytes; (2) kisspeptin-10: (i) inhibited cell proliferation, viability and adipogenesis in 3T3-L1 and decreased expression of PPAR-γ and CEBPβ—genes, which are involved in the differentiation processes and adipogenesis; (ii) increased lipolysis in 3T3-L1 cells and rat adipocytes by enhancing expression of periliphin and hormone-sensitive lipase; (iii) modulated glucose uptake and lipogenesis; (iv) stimulated leptin and decreased adiponectin secretion from rat adipocytes.
Conclusion
Kisspeptin-10 could play a role in the regulation of lipid metabolism in mouse 3T3-L1 cells and rat adipocytes.
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Hair cortisol in the evaluation of Cushing syndrome
Abstract
Purpose
Hair cortisol evaluation has been used to help detect patients with suspected Cushing syndrome. Our goal was to correlate segmental hair cortisol with biochemical testing in patients with Cushing syndrome and controls. This study was a prospective analysis of hair cortisol in confirmed Cushing syndrome cases over 16 months.
Methods
Thirty-six subjects (26.5 ± 18.9 years, 75% female, and 75% Caucasian) were analyzed by diurnal serum cortisol, 24 h urinary free cortisol corrected for body surface area (UFC/BSA), and 24 h urinary 17-hydroxysteroids corrected for creatinine (17OHS/Cr). Thirty patients were diagnosed with Cushing syndrome, and six were defined as controls. 3-cm hair samples nearest to the scalp, cut into 1-cm segments (proximal, medial, and distal), were analyzed for cortisol by enzyme immunoassay and measured as pmol cortisol/g dry hair. Hair cortisol levels were compared with laboratory testing done within previous 2 months of the evaluation.
Results
Proximal hair cortisol was higher in Cushing syndrome patients (266.6 ± 738.4 pmol/g) than control patients (38.9 ± 25.3 pmol/g) (p = 0.003). Proximal hair cortisol was highest of all segments in 25/36 (69%) patients. Among all subjects, proximal hair cortisol was strongly correlated with UFC/BSA (r = 0.5, p = 0.005), midnight serum cortisol (r = 0.4, p = 0.03), and 17OHS/Cr, which trended towards significance (r = 0.3, p = 0.06).
Conclusions
Among the three examined hair segments, proximal hair contained the highest cortisol levels and correlated the most with the initial biochemical tests for Cushing syndrome in our study. Further studies are needed to validate proximal hair cortisol in the diagnostic workup for Cushing syndrome.
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Urea assisted synthesis of Ni1−xZnxFe2O4 (0 ≤ x ≤ 0.8): Magnetic and Mössbauer investigations
Publication date: 15 May 2017
Source:Journal of Alloys and Compounds, Volume 704
Author(s): S.S. Deshmukh, Ashok V. Humbe, Arun Kumar, R.G. Dorik, K.M. Jadhav
The system as Ni1−xZnxFe2O4 where x = 0.0, 0.2, 0.4, 0.6 and 0.8 were prepared using sol-gel auto combustion method. A typical as-prepared sample was characterized by using TGA DTA. Then the as-prepared samples were annealed at 600 °C for 6 h in air atmosphere and used for further characterizations. The annealed samples were characterized by XRD, IR, FESEM-EDS and TEM. The magnetic measurements were carried out using pulse field hysteresis loop tracer technique and Mössbauer spectrometer at room temperature. The analysis of XRD patterns favored the formation of the single phase cubic spinel structure of the prepared Ni-Zn spinel ferrite nanoparticles. The structural parameters like lattice constant, crystallite size, X-ray density etc were evaluated using XRD data. The characteristic bands of spinel ferrite for tetrahedral and octahedral sites in IR spectra were observed. The primary analysis of the FESEM images for Ni-Zn spinel ferrite nanoparticles were suggested the agglomerated nature, fine size distribution and spherical geometry. The EDS spectra analysis showed the well matching of calculated and experimentally obtained elemental composition. Moreover, the particle size determination and morphology investigations (x = 0.0 and 0.4) were performed by TEM technique. The particle size obtained is in the order of 28–31 nm which also confirms the nanocrystalline nature of the prepared Ni-Zn spinel ferrite nanoparticles. Using the M − H curves the saturation magnetization, remanence magnetization, coercivity were obtained. Furthermore, other magnetic parameters as remenance ratio, magneton number, anisotropy constant, anisotropy field were determined using M − H data. Moreover, the magnetic investigations of Ni-Zn spinel ferrite nanoparticles were investigated by Mössbauer spectroscopy technique and the isomer shift, line width, hyperfine field, and quadrupole splitting were studied.
Graphical abstract
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In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging
Publication date: May 2017
Source:Neurobiology of Aging, Volume 53
Author(s): Mathijs Buijs, Nhat Trung Doan, Sanneke van Rooden, Maarten J. Versluis, Baldur van Lew, Julien Milles, Jeroen van der Grond, Mark A. van Buchem
Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22–80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases.
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White matter lesions and the cholinergic deficit in aging and mild cognitive impairment
Publication date: May 2017
Source:Neurobiology of Aging, Volume 53
Author(s): Nils Richter, Anne Michel, Oezguer A. Onur, Lutz Kracht, Markus Dietlein, Marc Tittgemeyer, Bernd Neumaier, Gereon R. Fink, Juraj Kukolja
In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [11C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment.
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A case-based reasoning system based on weighted heterogeneous value distance metric for breast cancer diagnosis
Source:Artificial Intelligence in Medicine
Author(s): Dongxiao Gu, Changyong Liang, Huimin Zhao
Currently, breast cancer diagnosis depends largely on physicians' experiential knowledge. By retrieving similar cases in a breast cancer decision support system, oncologists can obtain powerful information or knowledge, complementing their own experiential knowledge, in their medical decision making. In this paper, we present the implementation of a case-based reasoning (CBR) system for breast cancer related diagnoses and its application in two studies related to benign/malignant tumor prediction and secondary cancer prediction, respectively. We observed two problems in applying standard CBR to this context: the abundance of different types of attributes and the difficulty in eliciting appropriate attribute weights from human experts. We therefore used a distance measure named weighted heterogeneous value distance metric, which can better deal with both continuous and discrete attributes simultaneously than the standard Euclidean distance, and a genetic algorithm for learning the attribute weights involved in this distance measure automatically. Our evaluation based on two real-world breast cancer data sets indicates the potential of CBR in the breast cancer diagnosis domain.
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DisTeam: A decision support tool for surgical team selection
Source:Artificial Intelligence in Medicine
Author(s): Ashkan Ebadi, Patrick J. Tighe, Lei Zhang, Parisa Rashidi
ObjectiveSurgical service providers play a crucial role in the healthcare system. Amongst all the influencing factors, surgical team selection might affect the patients' outcome significantly. The performance of a surgical team not only can depend on the individual members, but it can also depend on the synergy among team members, and could possibly influence patient outcome such as surgical complications. In this paper, we propose a tool for facilitating decision making in surgical team selection based on considering history of the surgical team, as well as the specific characteristics of each patient.MethodsDisTeam (a decision support tool for surgical team selection) is a metaheuristic framework for objective evaluation of surgical teams and finding the optimal team for a given patient, in terms of number of complications. It identifies a ranked list of surgical teams personalized for each patient, based on prior performance of the surgical teams. DisTeam takes into account the surgical complications associated with teams and their members, their teamwork history, as well as patient's specific characteristics such as age, body mass index (BMI) and Charlson comorbidity index score.ResultsWe tested DisTeam using intra-operative data from 6065 unique orthopedic surgery cases. Our results suggest high effectiveness of the proposed system in a health-care setting. The proposed framework converges quickly to the optimal solution and provides two sets of answers: a) The best surgical team over all the generations, and b) The best population which consists of different teams that can be used as an alternative solution. This increases the flexibility of the system as a complementary decision support tool.ConclusionDisTeam is a decision support tool for assisting in surgical team selection. It can facilitate the job of scheduling personnel in the hospital which involves an overwhelming number of factors pertaining to patients, individual team members, and team dynamics and can be used to compose patient-personalized surgical teams with minimum (potential) surgical complications.
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Identification of adverse drug-drug interactions through causal association rule discovery from spontaneous adverse event reports
Source:Artificial Intelligence in Medicine
Author(s): Ruichu Cai, Mei Liu, Yong Hu, Brittany L. Melton, Michael E. Matheny, Hua Xu, Lian Duan, Lemuel R. Waitman
ObjectiveDrug-drug interaction (DDI) is of serious concern, causing over 30% of all adverse drug reactions and resulting in significant morbidity and mortality. Early discovery of adverse DDI is critical to prevent patient harm. Spontaneous reporting systems have been a major resource for drug safety surveillance that routinely collects adverse event reports from patients and healthcare professionals. In this study, we present a novel approach to discover DDIs from the Food and Drug Administration's adverse event reporting system.MethodsData-driven discovery of DDI is an extremely challenging task because higher-order associations require analysis of all combinations of drugs and adverse events and accurate estimate of the relationships between drug combinations and adverse event require cause-and-effect inference. To efficiently identify causal relationships, we introduce the causal concept into association rule mining by developing a method called Causal Association Rule Discovery (CARD). The properties of V-structures in Bayesian Networks are utilized in the search for causal associations. To demonstrate feasibility, CARD is compared to the traditional association rule mining (AR) method in DDI identification.ResultsBased on physician evaluation of 100 randomly selected higher-order associations generated by CARD and AR, CARD is demonstrated to be more accurate in identifying known drug interactions compared to AR, 20% vs. 10% respectively. Moreover, CARD yielded a lower number of drug combinations that are unknown to interact, i.e., 50% for CARD and 79% for AR.ConclusionEvaluation analysis demonstrated that CARD is more likely to identify true causal drug variables and associations to adverse event.
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Analysis of cancer-related lncRNAs using gene ontology and KEGG pathways
Source:Artificial Intelligence in Medicine
Author(s): Lei Chen, Yu-Hang Zhang, Guohui Lu, Tao Huang, Yu-Dong Cai
BackgroundCancer is a disease that involves abnormal cell growth and can invade or metastasize to other tissues. It is known that several factors are related to its initiation, proliferation, and invasiveness. Recently, it has been reported that long non-coding RNAs (lncRNAs) can participate in specific functional pathways and further regulate the biological function of cancer cells. Studies on lncRNAs are therefore helpful for uncovering the underlying mechanisms of cancer biological processes.MethodsWe investigated cancer-related lncRNAs using gene ontology (GO) terms and KEGG pathway enrichment scores of neighboring genes that are co-expressed with the lncRNAs by extracting important GO terms and KEGG pathways that can help us identify cancer-related lncRNAs. The enrichment theory of GO terms and KEGG pathways was adopted to encode each lncRNA. Then, feature selection methods were employed to analyze these features and obtain the key GO terms and KEGG pathways.ResultsThe analysis indicated that the extracted GO terms and KEGG pathways are closely related to several cancer associated processes, such as hormone associated pathways, energy associated pathways, and ribosome associated pathways. And they can accurately predict cancer-related lncRNAs.ConclusionsThis study provided novel insight of how lncRNAs may affect tumorigenesis and which pathways may play important roles during it. These results could help understanding the biological mechanisms of lncRNAs and treating cancer.
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Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management
AbstractBackground
A previously under-recognized subset of hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) apical aneurysms is being identified with increasing frequency. However, risks associated with this subgroup are unknown.
ObjectivesThe authors aimed to clarify clinical course and prognosis of a large cohort of HCM patients with LV apical aneurysms over long-term follow-up.
MethodsThe authors retrospectively analyzed 1,940 consecutive HCM patients at 2 centers, 93 of which (4.8%) were identified with LV apical aneurysms; mean age was 56 ± 13 years, and 69% were male.
ResultsOver 4.4 ± 3.2 years, 3 of the 93 patients with LV apical aneurysms (3%) died suddenly or of heart failure, but 22 (24%) survived with contemporary treatment interventions: 18 experienced appropriate implantable cardioverter-defibrillator discharges, 2 underwent heart transplants, and 2 were resuscitated after cardiac arrest. The sudden death event rate was 4.7%/year. Notably, recurrent monomorphic ventricular tachycardia requiring ≥2 implantable cardioverter-defibrillator shocks occurred in 13 patients, including 6 who underwent successful radiofrequency ablation of the arrhythmic focus without ventricular tachycardia recurrence. Five non-anticoagulated patients experienced nonfatal thromboembolic events (1.1%/year), whereas 13 with apical clots and anticoagulation did not incur embolic events. There was no consistent relationship between aneurysm size and adverse HCM-related events. Rate of HCM-related deaths combined with life-saving aborted disease-related events was 6.4%/year, 3-fold greater than the 2.0%/year event rate in 1,847 HCM patients without aneurysms (p < 0.001).
ConclusionsHCM patients with LV apical aneurysms are at high risk for arrhythmic sudden death and thromboembolic events. Identification of this phenotype expands risk stratification and can lead to effective treatment interventions for potentially life-threatening complications.
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Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences
Abstract
Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke. Several discoveries in the pathogenesis, along with developments in the treatment of sleep apnea, have accumulated in recent years. In this review, we discuss the mechanisms of sleep apnea, the evidence that addresses the links between sleep apnea and cardiovascular disease, and research that has addressed the effect of sleep apnea treatment on cardiovascular disease and clinical endpoints. Finally, we review the recent development in sleep apnea treatment options, with special consideration of treating patients with heart disease. Future directions for selective areas are suggested.
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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