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1.
Sensors (Basel) ; 23(12)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37420727

RESUMEN

Binarized Neural Network (BNN) is a quantized Convolutional Neural Network (CNN), reducing the precision of network parameters for a much smaller model size. In BNNs, the Batch Normalisation (BN) layer is essential. When running BN on edge devices, floating point instructions take up a significant number of cycles to perform. This work leverages the fixed nature of a model during inference, to reduce the full-precision memory footprint by half. This was achieved by pre-computing the BN parameters prior to quantization. The proposed BNN was validated through modeling the network on the MNIST dataset. Compared to the traditional method of computation, the proposed BNN reduced the memory utilization by 63% at 860-bytes without any significant impact on accuracy. By pre-computing portions of the BN layer, the number of cycles required to compute is reduced to two cycles on an edge device.


Asunto(s)
Redes Neurales de la Computación , Carrera
2.
J Community Health ; 46(4): 645-652, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-32778989

RESUMEN

The choice to take-up specific complimentary and alternative medicine (CAM) modalities is influenced by many factors including cultural background, experience and peer-participation. In this study we investigated the beliefs and attitudes that contributed to CAM choices in a non-urban Malaysian population (N = 700). We found significant differences in the beliefs held by men and women in this population. Specifically, women believed more strongly than men that CAM providers offered healthy lifestyle advice (p = 0.042) and that those who were averse to discomfort from conventional treatments were more likely to take up CAM (p = 0.016). In addition, those individuals who chose to use CAM more strongly believed that CAM products were more healthy than conventional treatments (p = 0.002), that their effects were well understood (p = 0.002) and that CAM products worked with the body (p = 0.017). The data obtained in this study emphasize the lessons that can be learned by conventional healthcare providers in communicating the benefits of treatments to their patients. CAM users also believed that CAM products never caused harm (p = 0.007), which is a concern given that the modes of action of some CAM modalities and their interaction with prescribed treatments are not always well understood.


Asunto(s)
Terapias Complementarias , Conocimientos, Actitudes y Práctica en Salud , Femenino , Personal de Salud , Humanos , Masculino , Grupo Paritario , Factores Sexuales
3.
J Community Health ; 46(3): 515-521, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32710232

RESUMEN

Complementary and alternative medicine (CAM) therapies have been an integral part of Malaysia culture for many centuries. In recent years influences from other parts of the world have gained a foot-hold in Malaysian popular culture. We investigated the engagement with CAM in a non-urban, Malaysian population. We investigated the association of CAM use with cultural influence, perceived health status, gender and age. We recruited 700 adult participants to this study across three sites in central Malaysia. We found massage, Vitamin supplements, Herbal medicine and traditional Chinese medicine to be the most popular CAM modalities with participation at 67.7%, 55.7%, 55.5% and 26.3% respectively. CAM use was equally high at 67% among those people who claimed a predominantly Malay or Chinese cultural influence. The use of vitamins and participation in yoga were at higher prevalence among female participants compared to males. There was no gender difference for other CAM modalities. There were differences between age groups for most CAM modalities, and those over 50 years tended to be the highest frequency users for most modalities. There is a high rate of CAM use in non-urban Malaysia with younger people being more engaged with less traditional modalities such as aromatherapy, yoga and music therapy.


Asunto(s)
Terapias Complementarias , Adulto , Estudios Transversales , Femenino , Medicina de Hierbas , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Prevalencia
4.
Nucleic Acids Res ; 45(D1): D204-D209, 2017 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-27507885

RESUMEN

ADP-ribosylation refers to the addition of one or more ADP-ribose units onto proteins post-translationally. This protein modification is often added by ADP-ribosyltransferases, commonly known as PARPs, but it can also be added by other enzymes, including sirtuins or bacterial toxins. While past literature has utilized a variety of methods to identify ADP-ribosylated proteins, recent proteomics studies bring the power of mass spectrometry to determine sites of the modification. To appreciate the diverse roles of ADP-ribosylation across the proteome, we have created ADPriboDB - a database of ADP-ribosylated proteins (http://ADPriboDB.leunglab.org). Each entry of ADPriboDB is annotated manually by at least two independent curators from the literature between January 1975 and July 2015. The current database includes over 12 400 protein entries from 459 publications, identifying 2389 unique proteins. Here, we describe the structure and the current state of ADPriboDB as well as the criteria for entry inclusion. Using this aggregate data, we identified a statistically significant enrichment of ADP-ribosylated proteins in non-membranous RNA granules. To our knowledge, ADPriboDB is the first publicly available database encapsulating ADP-ribosylated proteins identified from the past 40 years, with a hope to facilitate the research of both basic scientists and clinicians to better understand ADP-ribosylation at the molecular level.


Asunto(s)
ADP-Ribosilación , Bases de Datos de Proteínas , Procesamiento Proteico-Postraduccional , Animales , Bibliometría , Predicción , Humanos , Proteoma
6.
J Med Radiat Sci ; 71 Suppl 2: 10-18, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37622485

RESUMEN

INTRODUCTION: Travelling for cancer treatment comes with unique challenges, particularly for a young patient and his or her family. The aims of this study were to (1) gain an understanding of the experiences of families and patients who travelled overseas (OS) from Australia for proton beam therapy (PBT) and (2) identify the supportive care needs patients and their families require when living away from home, while having PBT. METHODS: This was a retrospective, qualitative study using semi-structured interviews, conducted with participants aged under 25 years and their families who travelled OS for PBT between 2017 and 2020. Data were analysed using Microsoft Excel Software, where key themes were identified and coded based on their responses. A total of 17 participants were included in interviews from seven Australian families who travelled to America or Europe for PBT. RESULTS: The majority of participants reported a lack of coordination with travel and treatment arrangements prior to arrival OS. Families who stayed in hotel accommodation while OS reported greater feelings of isolation compared with those who stayed in share house-style accommodation. The acuity of cancer diagnosis played a significant part in patient experience, with those patients requiring the greatest amount of supportive care and availability of service provision at stand-alone centres reporting a lack of appropriate care provision. CONCLUSIONS: This study has identified services, accommodation provisions and care coordination requirements that are largely missing from the travel and treatment experience in patients travelling OS for PBT. Future use of consumer-led working groups or committees in creating models of care for families travelling for PBT treatment could be advantageous, with many families willing to share their experiences and provide support to others who are travelling for PBT.


Asunto(s)
Terapia de Protones , Humanos , Masculino , Femenino , Anciano , Australia , Estudios Retrospectivos , Viaje , Investigación Cualitativa
7.
Asia Pac J Clin Oncol ; 19(4): 525-532, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36464920

RESUMEN

INTRODUCTION: The Australian Bragg Centre for Proton Therapy and Research (ABCPTR) will be Australia's first proton beam therapy (PBT) facility. A model was developed to predict associated public hospital care requirements for patients during PBT, to facilitate resource planning for pediatric, adolescent and young adult (AYA), and adult public hospitals in South Australia. METHODS: National incidence rates for specific cancer indications were obtained from the Australian Childhood Cancer Registry, Australian Institute of Health and Welfare and published data. Australian Bureau of Statistics national population projections were used to estimate new cases in 2025 and beyond. Radiation oncologists and pediatric oncologists from the Central Adelaide Local and Women's and Children's Health Network, along with international colleagues, provided guidance on chemotherapy utilization and inpatient admission estimates. RESULTS: It was estimated 180 patients (40.4%) within the adult population (≥25 years) and 265 patients (59.6%) within the pediatric/AYA population (<25 years) would be eligible for PBT in 2025. There was no indication adult cancers would require concurrent outpatient/inpatient chemotherapy, in contrast with pediatric and AYA patients (59.5% and 62.8% outpatient and 18.9% and 41.9% inpatient, respectively). It was estimated 53% and 29% of pediatric and AYA patients could require inpatient admission for toxicity related to disease, concurrent chemotherapy or PBT. CONCLUSION: Associated public hospital care requirements related to the delivery of a national PBT service were estimated. This has particular implications for planning of the new Women's and Children's hospital, co-located with the ABCPTR. True data accuracy will be determined on future data generation and analysis.


Asunto(s)
Neoplasias , Terapia de Protones , Adolescente , Adulto Joven , Humanos , Niño , Femenino , Terapia de Protones/efectos adversos , Salud Infantil , Australia/epidemiología , Salud de la Mujer , Neoplasias/epidemiología , Neoplasias/radioterapia , Neoplasias/etiología
8.
Artículo en Inglés | MEDLINE | ID: mdl-38146017

RESUMEN

Proton Beam Therapy (PBT) has the potential to improve paediatric cancer care by reducing radiation exposure and thus long-term toxicities. Ethical concerns and debates surrounding the treatment, such as eligibility and accessibility, are ongoing in Australia. The Australian Bragg Centre for Proton Therapy and Research (ABCPTR) (named after Sir William Henry Bragg who described the Bragg peak in his laboratory at the University of Adelaide in 1903) aims to increase access to PBT in Australasia and offer a patient-centred care approach. Research is underway to assess PBT's safety and cost-effectiveness, using tools including Normal Tissue Complication Probability (NTCP) models. Collaborative efforts are focused on developing tailored survivorship clinics to enhance patient follow-up and quality of life. With the anticipated opening of the ABCPTR, Australia is preparing to take a significant step in radiation oncology, offering new research opportunities and creating a publicly funded treatment centre. The initiative aims to balance treatment efficacy with patient care, setting the stage for a future in which radiation therapy will reduce long-term side effects compared to the current standard of care. The implementation of PBT in Australia represents a complex and promising approach to paediatric oncology. This article provides an overview of the current landscape, highlighting the potential benefits and challenges of a treatment that could redefine the quality of survivorship and contribute to global research and best clinical practice.

9.
Eur J Hum Genet ; 30(1): 7-12, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33840813

RESUMEN

Hearing loss (HL) is one of the most common sensory defects, of which X-linked nonsyndromic hearing loss (NSHL) accounts for only 1-2%. While a COL4A6 variant has been reported in a single Hungarian family with NSHL associated with inner ear malformation, causative role of COL4A6 variants and their phenotypic consequences in NSHL remain elusive. Here we report two families in which we identified a male member with X-linked HL. Each has inherited a rare hemizygous COL4A6 variant from their respective mothers, NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951 + 1 G > C. An in vitro minigene splicing assay revealed that c.951 + 1 G > T leads to skipping of exon 15, strongly suggesting a pathogenic role for this variant in the HL phenotype. The p.Gly1091Ala variant is classified as a variant of unknown significance based on the variant interpretation guidelines. This report provides evidence for variants in the COL4A6 gene resulting in X-linked NSHL. It highlights the importance of in-depth genetic studies in all family members in addition to the proband, especially in multiplex families, to determine the precise etiology of HL.


Asunto(s)
Colágeno Tipo IV/genética , Pérdida Auditiva Sensorineural/genética , Femenino , Pérdida Auditiva Sensorineural/patología , Hemicigoto , Humanos , Masculino , Mutación Missense , Linaje
10.
J Med Entomol ; 48(4): 797-805, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21845938

RESUMEN

The population size, age-class structure, and movement of the American cockroach, Periplaneta americana (L.) (Dictyoptera: Blattidae), were studied in three sewers in Penang, Malaysia, from September 2008 to October 2009. Eighteen to 20 glass-jar traps (two per manhole) were deployed for a 24-h period during each sampling occasion at each sewer. Adults and nymphs were active throughout the study period, with an average monthly trap catch of 57-97 adults and 79-99 nymphs. The mean proportions of adults and nymphs at the three sewers ranged from 0.47 to 0.57. Of the 2177 male and 2717 female cockroaches marked and released over the three sewers, recapture rates were 29.4-45.8 and 30.8-47.0%, respectively. The proportion of marked males and females did not differ significantly from the proportion of recaptured marked males and females. However, the mean number of times a marked female was recaptured was significantly greater than that of males. Of the 783 males and 1,030 females that were marked and recaptured, 19.4 and 24.7%, respectively, had moved between manholes, and significantly more females than males moved between manholes. Of the 406 recaptured marked adults that moved between manholes, 90.4% moved a distance of 2-20 m from their initial release site; one male moved 192 m, the longest distance recorded. Trap catch on each sampling occasion was positively correlated with daily mean temperature. The number of cockroach movements between manholes also was correlated with the mean daily minimum temperature.


Asunto(s)
Periplaneta/fisiología , Animales , Drenaje de Agua , Femenino , Malasia , Masculino , Movimiento , Ninfa/fisiología , Dinámica Poblacional , Distribución por Sexo
11.
J Econ Entomol ; 104(6): 2031-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22299367

RESUMEN

The objective of this study was to evaluate the potential of Aprostocetus hagenowii (Ratzeburg) (Hymenoptera: Eulophidae) to control American cockroaches, Periplaneta americana (L.) (Dictyoptera: Blattidae), in sewer manholes and in crevices around buildings. Parasitoids were released weekly for 12 wk from laboratory parasitized heat-killed oothecae, and parasitism monitored using sentinel oothecae of American cockroaches. In addition, preference of A. hagenowii for 1- to 4-wk-old oothecae was evaluated in the laboratory. A. hagenowii females showed no preference for any ootheca age. Twenty of the 30 tested females parasitized one ootheca, whereas the other 10 parasitized two oothecae. The total progeny (males, females, and total) that emerged from a single ootheca parasitized by a female was not significantly different to the total progeny that emerged from two oothecae parasitized by a female. The number of males, females, and total progeny that emerged from the second parasitized ootheca was significantly less than the number that emerged from the first parasitized ootheca. The weekly mean sentinel oothecal parasitism rate in wall crevices was 18.1 +/- 3.2% and in sewer manholes was 13.3 +/- 2.0%. The mean number of released A. hagenowii females per number of parasitized sentinel oothecae recorded in crevices was 189 +/- 18, whereas it was 428 +/- 50 in sewers. A. hagenowii females were more effective at parasitizing sentinel oothecae placed at high and middle levels in manholes than at a low level when releases were made at the midpoint of the manhole shaft.


Asunto(s)
Periplaneta/parasitología , Control Biológico de Vectores/métodos , Avispas/fisiología , Animales , Espacios Confinados , Drenaje de Agua , Femenino , Vivienda , Malasia , Masculino , Oviposición , Óvulo/parasitología , Óvulo/fisiología , Periplaneta/fisiología , Estaciones del Año
12.
J Clin Pharmacol ; 61(1): 25-31, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32648298

RESUMEN

Severe drug hypersensitivity reactions (DHRs) are often encountered by health care professionals (HCPs). We evaluated knowledge of doctors and pharmacists in the assessment and management of severe DHRs using a structured questionnaire. A cross-sectional study was conducted in 4 metropolitan hospital networks in Melbourne, Australia. A 13-question, scenario-based multiple-choice questionnaire to assess specific knowledge domains in drug hypersensitivity syndrome recognition, causality attribution, cross-reactivity patterns, appropriate diagnostic tests, and therapy was administered to HCPs of various vocation and specialty groups. Data were analyzed according to profession, self-reported experience, and preparedness in managing severe DHRs. Two hundred thirty-eight participants (45.0% senior doctors, 24.4% junior doctors, and 30.7% pharmacists) across a range of subspecialties achieved an overall median score of 7 (IQR, 5-8)-overall 55.6% correct responses to all questions-with senior doctors outperforming junior doctors and pharmacists (P < .001). The best performance by all participants was in DHR syndrome recognition (60.9%), and the poorest was in diagnostics/therapy (52.0%). HCP group and experience level were significantly associated with better performance in the knowledge domains of cross-reactivity and diagnostics/therapy (P = .003 and < .001, respectively), but not in the domains of syndrome recognition and causality attribution (P > .05). Levels of self-reported preparedness in DHR management were not associated with performance rates in any of the knowledge domains. This study demonstrated significant knowledge gaps in the recognition and management of severe drug hypersensitivity reactions. Targeted multidisciplinary education of staff caring for these patients is needed to improve knowledge gaps.


Asunto(s)
Hipersensibilidad a las Drogas/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Australia , Reacciones Cruzadas , Estudios Transversales , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/fisiopatología , Hipersensibilidad a las Drogas/terapia , Humanos
13.
Polymers (Basel) ; 13(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806990

RESUMEN

Geopolymer coating using rice husk ash (RHA) as the aluminosilicate source has shown excellent fire retardant properties. However, incorporation of rice husk ash into the geopolymer matrix increased water absorption properties of the polymer composite. As such, silicone rubber (SiR) was introduced to improve the moisture absorption and fire retardant properties of the composite. Additionally, the less efficient one-factor-at-a-time (OFAT) approach was conventionally used in past studies on the RHA-based geopolymer composite. In understanding the optimum value and significant effect of factors on the fire retardant and moisture absorption properties of the binary blended geopolymer coating composite, the use of statistical analysis and regression coefficient model (mathematical model) was considered essential. The objectives of this study are to identify the significant effect of factors on moisture absorption and fire retardant properties, to determine the optimum composition, and to study the microstructure of the rice husk ash/silicone rubber (RHA/SiR)-based binary blended geopolymer coating composite. The RHA/AA and SiR/Ge ratios were chosen as factors, and the response surface methodology (RSM) was employed to design experiments and conduct analyses. Fire retardant and moisture absorption tests were conducted. A scanning electron microscope (SEM) was used to observe the microstructure of geopolymer samples. The RHA/alkaline activator (AA) and SiR/Ge ratios were shown to have a significant effect on the responses (temperature at equilibrium and moisture absorption). The high ratio of RHA/AA and SiR/Ge resulted in a lower temperature at equilibrium (TAE) below 200°C and at moisture absorption below 16%. The optimum formulation for the geopolymer coating composite can be achieved when the RHA/AA ratio, SiR/Ge ratio, and sodium hydroxide concentration are set at 0.85, 0.70, and 14 M, respectively. SEM micrographs of samples with good fire retardant properties showed that the char residue of the geopolymer composite coating, which is a layer of excess silicone rubber, is porous and continuous, thus providing a shielding effect for the layer of geopolymer underneath. The sample with good moisture absorption showed the formation of a thin outer layer of silicone rubber without any cracks. The unreacted SiR formed a thin layer beneath the geopolymer composite matrix providing a good moisture barrier.

14.
J Econ Entomol ; 103(5): 1770-4, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21061978

RESUMEN

The objective of this study was to evaluate the suitability of heat- and freeze-killed oothecae of Periplaneta americana (L.) (Dictyoptera: Blattidae) as hosts for parasitoid Aprostocetus hagenowii (Ratzeburg) (Hymenoptera: Eulophidae). The oothecae were subjected to -20, 45, 48, 50, and 55 degrees C at different exposure times (15, 30, 45, and 60 min). The effects of heat- and freeze-killed oothecae on several biological parameters (e.g., parasitism and emergence rates, developmental times, progeny number, and sex ratio) ofA. hagenowii were determined. Embryonic development of 2-d-old oothecae was terminated by either freezing at -20 degrees C or heating at > or = 48 degrees C for > or =30 min. A. hagenowii parasitized live oothecae as well as both heat- and freeze-killed oothecae. Percentage parasitism, emergence rates, and developmental times ofA. hagenowii in both heat- and freeze-killed oothecae were not significantly different from those of the live oothecae. Both heating and freezing did not influence progeny number (male and female) and sex ratio of A. hagenowii emerged from killed oothecae.


Asunto(s)
Himenópteros/crecimiento & desarrollo , Periplaneta/parasitología , Animales , Embrión no Mamífero , Congelación , Interacciones Huésped-Parásitos , Calor , Control de Insectos/métodos
15.
J Med Imaging Radiat Oncol ; 64(5): 682-688, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32243727

RESUMEN

INTRODUCTION: Australia's first proton beam therapy (PBT) service, The Australian Bragg Centre for Proton Therapy and Research, is scheduled to open in the near future providing PBT for patients closer to home. Patients currently access Commonwealth funding for PBT via the Medicare Medical Treatment Overseas Program (MTOP). Proton versus photon treatment planning is a pre-requisite for the MTOP application. The Royal Adelaide Hospital (RAH) Department of Radiation Oncology has been providing this since 2016. We aim to provide a descriptive overview of our proton versus photon treatment planning process, presenting a summary of the comparative planning results and the treatment pathways selected for the patients referred. METHODS: All patients referred to the RAH for comparative planning between January 2016 and December 2018 were included in the analysis. Comparative plans were generated for each case using Pinnacle or Eclipse treatment planning systems. The planning techniques used and plan quality metrics were reported. RESULTS: Forty three patients were referred for comparative planning. The age range was 1-63 years, with the majority (72%) being paediatric patients (age ≤18 years). Of the 19 cases that have been submitted to MTOP, 16 have been accepted and 3 denied. Two of the accepted cases chose not to travel abroad for PBT. The other 14 cases have received PBT overseas. CONCLUSIONS: The RAH has provided an important service to demonstrate the dosimetric difference between PBT and photon therapy for Australian patients, an important step in supporting the funding of patients for treatment overseas.


Asunto(s)
Neoplasias/radioterapia , Terapia de Protones , Oncología por Radiación/métodos , Adolescente , Adulto , Australia , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Fotones , Planificación de la Radioterapia Asistida por Computador
16.
Australas Phys Eng Sci Med ; 42(4): 1091-1098, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31646441

RESUMEN

While proton beam therapy (PBT) can offer increased sparing of healthy tissue, it is associated with large capital costs and as such, has limited availability. Furthermore, it has not been well established whether PBT has significant clinical advantages over conventional volumetric modulated arc therapy (VMAT) for all tumour types. PBT can potentially offer improved clinical outcomes for base of skull chordoma (BOSCh) patients compared with photon (X-ray) therapy, however the cost-effectiveness of these treatments is unclear. In this study, the cost-effectiveness of PBT in the treatment of BOSCh patients is assessed, based on an analysis of comparative radiotherapy treatment plans using a radiobiological Markov model. Seven BOSCh patients had treatment plans for the delivery of intensity modulated proton therapy and VMAT retrospectively analysed. The patient outcome (in terms of tumour local control and normal tissue complications) after receiving each treatment was estimated with a radiobiological Markov model. In addition, the model estimated the cost of both the primary treatment and treating any resultant adverse events. The incremental cost-effectiveness ratio (ICER) was obtained for each patient. PBT was found to be cost-effective for 5 patients and cost-saving for 2. The mean ICER was AUD$1,990 per quality adjusted life year gained. Variation of model parameters resulted in the proton treatments remaining cost-effective for these patients. Based on this cohort, PBT is a cost-effective treatment for patients with BOSCh. This supports the inclusion of PBT for BOSCh in the Medicare Services Advisory Committee 1455 application.


Asunto(s)
Cordoma/economía , Cordoma/terapia , Análisis Costo-Beneficio , Terapia de Protones/economía , Neoplasias de la Base del Cráneo/economía , Neoplasias de la Base del Cráneo/terapia , Adulto , Niño , Preescolar , Estudios de Cohortes , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Cadenas de Markov , Persona de Mediana Edad , Probabilidad , Calidad de Vida
17.
Bioorg Med Chem ; 16(1): 171-80, 2008 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-17964170

RESUMEN

A library of chalcones with basic functionalities were screened for inhibition of P-glycoprotein (Pgp, ABCB1) by the calcein-AM accumulation assay on MDCKII/MDR1 cells. Three members that had ring A substituted with 5-(1-ethylpiperidin-4-yl) and 2,4-dimethoxy groups were found to increase calcein-AM accumulation to a greater extent than verapamil, a Pgp inhibitor. These compounds were subsequently shown to enhance the uptake of doxorubicin by MCF-7 cells that over-expressed Pgp. However, when tested for inhibition of the breast cancer resistance protein (BCRP, ABCG2) by the mitoxantrone uptake assay, the same compounds fared poorly. In comparison, a non-basic chalcone (5-14, 3-(4-chlorophenyl)-1-(2,4-dimethoxyphenyl)prop-2-en-1-one) increased mitoxantrone uptake by BCRP over-expressing MCF-7 cells (MCF-7/MX) by more than 300% at 5 microM. Thus, introducing a basic group on the chalcone template enhanced Pgp inhibition at the expense of BCRP inhibition. The basic chalcones were also better Pgp inhibitors than their non-basic counterparts which may in turn be better BCRP inhibitors. Structure activity analysis showed that lipophilicity of the chalcones was not the overriding factor for Pgp inhibitory activity. Rather, good activity was associated with appropriately placed electron donor atoms, of which the meta-disubstituted dimethoxy motif on either ring A or B was of particular relevance. In spite of differing structural requirements for inhibition of Pgp and BCRP, chalcone 3-100 [3-(2,4-dimethoxyphenyl)-1-(4-(piperazin-1-yl)phenyl)prop-2-en-1-one] inhibited both Pgp and BCRP to a reasonable extent and may be a useful starting point for the design of dual inhibitors.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Chalconas/farmacología , Resistencia a Antineoplásicos , Proteínas de Neoplasias/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Línea Celular , Línea Celular Tumoral , Chalconas/química , Electrones , Humanos , Bibliotecas de Moléculas Pequeñas , Relación Estructura-Actividad
18.
J Clin Pharmacol ; 58(10): 1332-1339, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29733431

RESUMEN

We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2-year period (2015-2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1-10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4-5.5, and P = .04, OR 4.2, 95%CI 1.2-18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9-7.9, and P < .0001, OR 11.4, 95%CI 4.6-27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Personal de Salud , Seguridad del Paciente , Farmacovigilancia , Australia/epidemiología , Humanos , Estudios Retrospectivos
19.
J Econ Entomol ; 110(6): 2504-2511, 2017 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-29029091

RESUMEN

Many female parasitoid wasps optimize host selection to balance the benefits of high-quality hosts and the costs of predator- or hyperparasitoid-induced mortality risks to maximize their fitness. Cannibalism exists in many insect species and affects survival of parasitoid larvae developing in or on parasitized hosts. However, little is known about how parasitoid wasps resolve the fitness consequence of host cannibalism-induced mortality risk during host selection. We examined the effect of oothecal age on cannibalism in the American cockroach Periplaneta americana (L.) (Dictyoptera: Blattidae) and its effect on host age selection and fitness of its oothecal parasitoid Evania appendigaster (L.) (Hymenoptera: Evaniidae). P. americana differentially cannibalized 1-d-old (30‒60%) versus 10- to 40-d-old oothecae (<9%). However, parasitoid females did not avoid but still preferred to parasitize 1-d-old (45%) over 10- to 40-d-old oothecae (1.6‒20%). The parasitism rate was greater and the handling time was shorter on 1-d-old compared to older oothecae. For parasitoid progeny emerging from different-aged oothecae, regression analysis showed that development time increased and body size (measured as hind tibia length) and longevity decreased with oothecal age. These results demonstrate that reduced parasitoid progeny survival due to host cannibalism did not change the parasitoid's oviposition preference for newly laid oothecae, and that E. appendigaster females traded progeny survival for fitness gains for themselves and their progeny.


Asunto(s)
Oviposición , Periplaneta/crecimiento & desarrollo , Periplaneta/parasitología , Avispas/fisiología , Animales , Canibalismo , Femenino , Aptitud Genética , Interacciones Huésped-Parásitos , Larva/crecimiento & desarrollo , Larva/fisiología , Masculino , Ninfa/crecimiento & desarrollo , Ninfa/parasitología , Óvulo/crecimiento & desarrollo , Óvulo/parasitología , Avispas/genética , Avispas/crecimiento & desarrollo
20.
J Econ Entomol ; 110(1): 213-220, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28028170

RESUMEN

The influences of ootheca age and temperature on the life history of Aprostocetus hagenowii (Ratzeburg) (Hymenoptera: Eulophidae), a gregarious ootheca parasitoid of the American cockroach Periplaneta americana (L.) (Dictyoptera: Blattidae), were evaluated. Oothecae were incubated at 20, 25, and 30 °C to produce oothecae aged 1-60, 1-40, and 1-30 d old, respectively. Fitness traits (development time, percentage emergence, number of progeny, percentage female progeny, and female body size) of A. hagenowii developing in these different-aged oothecae were determined. For oothecae incubated at 20, 25, and 30 °C, parasitoids successfully developed in oothecae aged up to 50, 30, and 20 d old, which represent 72.9%, 65.9%, and 61.9% of the total embryonic development time of P. americana, respectively, without any changes in their fitness traits. When A. hagenowii from oothecae kept at constant temperatures (20, 25, 30, 32, and 35 °C) were compared, the immature development time (71.0-34.0 d) and adult life span decreased with increasing temperature. No parasitoid emerged at 35 °C. The lower, upper, and optimal temperature-dependent developmental thresholds were 9.5, 34.2, and 31.1 °C, respectively. Thermal constant for total immature development was 666.7 degree-days. Temperature did not affect lifetime realized fecundity and number of oothecae parasitized by females but did influence parasitism activities over time. Sugar-fed females sustained longer periods of high parasitism rates (≥70%) at 20-30 °C (15-30 d) than at 32-35 °C (1-5 d). These results are useful for determining the ootheca age and temperature range optimal for parasitoid rearing and for estimating the effectiveness of biological control by the wasps.


Asunto(s)
Interacciones Huésped-Parásitos , Rasgos de la Historia de Vida , Periplaneta/fisiología , Periplaneta/parasitología , Avispas/fisiología , Animales , Femenino , Fertilidad , Masculino , Óvulo/crecimiento & desarrollo , Óvulo/parasitología , Temperatura
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