Search

This study makes an ecological economic comparison between three different rice farming strategies in the Mekong Delta. Interviews were made with 30 farmers with two crops of rice and low dikes (2RLd), 30 farmers with three crops of rice and high dikes (3RHd) and 18 farmers with two crops of rice and one crop of fish (2RF). 2RF farmers had the highest annual net income and benefit cost ratio, because of low production costs and high yields of rice and fish. 2RLd farmers had the lowest annual net income. 3RHd had the highest annual rice yield, but also used the highest amount of rice seeds and agrochemicals, generating the lowest benefit cost ratio. Most farmers (70%) preferred two crops because of a higher production efficiency. High dikes and frequent use of pesticides and fertilizers were seen to decrease the water and rice quality, connectivity and biodiversity in farms with three crops. It is concluded that rice farming with two crops, and especially if integrated with fish and applying IPM, provides a sustainable alternative to rice farming with three crops and high dikes, because it makes use of the high connectivity within the rice-field ecosystem for an efficient production of healthy food through increased recycling of nutrients and  natural pest control mechanisms., (© 2023. The Author(s).)

The p53 transcription factor is a master regulator of cellular responses to stress that is commonly inactivated in diverse cancer types. Despite decades of research, the mechanisms by which p53 impedes tumorigenesis across vastly different cellular contexts requires further investigation. The bulk of research has been completed using in vitro studies of cancer cell lines or in vivo studies in mouse models, but much less is known about p53 action in diverse non-transformed human tissues. Here, we investigated how different cellular states modify the p53 transcriptional program in human cells through a combination of computational analyses of publicly available large-scale datasets and in vitro studies using an isogenic system consisting of induced pluripotent stem cells (iPSCs) and two derived lineages. Analysis of publicly available mRNA expression and genetic dependency data demonstrated wide variation in terms of expression and function of a core p53 transcriptional program across various tissues and lineages. To monitor the impact of cell differentiation on the p53 transcriptome within an isogenic cell culture system, we activated p53 by pharmacological inhibition of its negative regulator MDM2. Using cell phenotyping assays and genome wide transcriptome analyses, we demonstrated that cell differentiation confines and modifies the p53 transcriptional network in a lineage-specific fashion. Although hundreds of p53 target genes are transactivated in iPSCs, only a small fraction is transactivated in each of the differentiated lineages. Mechanistic studies using small molecule inhibitors and genetic knockdowns revealed the presence of two major regulatory mechanisms contributing to this massive heterogeneity across cellular states: gene silencing by epigenetic regulatory complexes and constitutive transactivation by lineage-specific transcription factors. Altogether, these results illuminate the impact of cell differentiation on the p53 program, thus advancing our understanding of how this tumor suppressor functions in different contexts., (© 2023. The Author(s).)

Inactivation of the p53 tumor suppressor, either by mutations or through hyperactivation of repressors such as MDM2 and MDM4, is a hallmark of cancer. Although many inhibitors of the p53-MDM2/4 interaction have been developed, such as Nutlin, their therapeutic value is limited by highly heterogeneous cellular responses. We report here a multi-omics investigation of the cellular response to MDM2/4 inhibitors, leading to identification of FAM193A as a widespread regulator of p53 function. CRISPR screening identified FAM193A as necessary for the response to Nutlin. FAM193A expression correlates with Nutlin sensitivity across hundreds of cell lines. Furthermore, genetic codependency data highlight FAM193A as a component of the p53 pathway across diverse tumor types. Mechanistically, FAM193A interacts with MDM4, and FAM193A depletion stabilizes MDM4 and inhibits the p53 transcriptional program. Last, FAM193A expression is associated with better prognosis in multiple malignancies. Altogether, these results identify FAM193A as a positive regulator of p53., Competing Interests: Declaration of interests J.M.E. has provided consulting services for Elli Lily and Co. and Gilead Sciences Inc. and serves on the advisory board of Perha Pharmaceuticals and on the editorial board of Cell Reports., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Little is known about the association between a mixture of heavy metals and obesity among individuals ≥50 years of age with comorbidities. Thus, we identified the associations of serum cadmium (Cd), lead (Pb), and mercury (Hg) with obesity using linear regression models; weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted as secondary analyses. Of the 6434 subjects included in the analysis, 13.8% had obesity and 44.6% had abdominal obesity. In the logistic regression model, serum Hg was associated with obesity and abdominal obesity, and significant trends were observed for these heavy metal tertiles (p < 0.001). Serum Hg levels were also associated with body mass index (BMI) and waist circumference (WC). The WQS index was significantly associated with both obesity (OR = 1.43, 95% CI: 1.40-1.46) and abdominal obesity (β = 1.51, 95% CI: 1.48-1.54). The qgcomp index also found a significant association between heavy metals and both obesity (OR = 1.35, 95% CI: 1.12-1.63) and abdominal obesity (OR = 1.34, 95% CI: 1.12-1.60). Serum Hg was the most heavily weighed heavy metal in these models. In BKMR analysis, the overall effect of the mixture was significantly associated with obesity, BMI, and WC. Serum Hg showed positive trends and was observed as the most important factor associated with obesity, BMI, and WC. Our findings were largely robust to secondary analyses that used three novel mixture modeling approaches: WQS, qpcomp, and BKMR. Given increasing exposure to heavy metals, well-characterized cohorts of individuals aged ≥50 years are required to determine the mixed effects of heavy metals on obesity and related diseases., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Trisomy 21, the source of Down syndrome, causes a 0.5-fold protein increase of the chromosome 21-resident gene Pericentrin (PCNT) and reduces primary cilia formation and signaling. We investigate how PCNT imbalances disrupt cilia. Using isogenic RPE-1 cells with increased chromosome 21 dosage, we find PCNT accumulates around the centrosome as a cluster of enlarged cytoplasmic puncta that localize along microtubules (MTs) and at MT ends. Cytoplasmic PCNT puncta impact the density, stability, and localization of the MT trafficking network required for primary cilia. The PCNT puncta appear to sequester cargo peripheral to centrosomes in what we call pericentrosomal crowding. The centriolar satellite proteins PCM1, CEP131, and CEP290, important for ciliogenesis, accumulate at enlarged PCNT puncta in trisomy 21 cells. Reducing PCNT when chromosome 21 ploidy is elevated is sufficient to decrease PCNT puncta and pericentrosomal crowding, reestablish a normal density of MTs around the centrosome, and restore ciliogenesis to wild-type levels. A transient reduction in MTs also decreases pericentrosomal crowding and partially rescues ciliogenesis in trisomy 21 cells, indicating that increased PCNT leads to defects in the MT network deleterious to normal centriolar satellite distribution. We propose that chromosome 21 aneuploidy disrupts MT-dependent intracellular trafficking required for primary cilia.

Fusarium is one of the most important fungal genera of plant pathogens that affect the cultivation of a wide range of crops. Agricultural losses caused by Fusariumoxysporumf.sp.cubense ( Foc ) directly affect the income, subsistence, and nourishment of thousands of farmers worldwide. For Viet Nam, predictions on the impact of Foc for the future are dramatic, with an estimated loss in the banana production area of 8% within the next five years and up to 71% within the next 25 years. In the current study, we applied a combined morphological-molecular approach to assess the taxonomic identity and phylogenetic position of the different Foc isolates collected in northern Viet Nam. In addition, we aimed to estimate the proportion of the different Fusarium races infecting bananas in northern Viet Nam. The morphology of the isolates was investigated by growing the collected Fusarium isolates on four distinct nutritious media (PDA, SNA, CLA, and OMA). Molecular phylogenetic relationships were inferred by sequencing partial rpb1 , rpb2 , and tef1a genes and adding the obtained sequences into a phylogenetic framework. Molecular characterization shows that c. 74% of the Fusarium isolates obtained from infected banana pseudostem tissue belong to F.tardichlamydosporum . Compared to F.tardichlamydosporum , F.odoratissimum accounts for c.10% of the Fusarium wilt in northern Viet Nam, demonstrating that Foc TR4 is not yet a dominant strain in the region. Fusariumcugenangense - considered to cause Race 2 infections among bananas - is only found in c. 10% of the tissue material that was obtained from infected Vietnamese bananas. Additionally, one of the isolates cultured from diseased bananas was phylogenetically not positioned within the F.oxysporum species complex (FOSC), but in contrast, fell within the Fusariumfujikuroi species complex (FFSC). As a result, a possible new pathogen for bananas may have been found. Besides being present on several ABB 'Tay banana', F.tardichlamydosporum was also derived from infected tissue of a wild Musalutea , showing the importance of wild bananas as a possible sink for Foc ., (Loan Le Thi, Arne Mertens, Dang Toan Vu, Tuong Dang Vu, Pham Le Anh Minh, Huy Nguyen Duc, Sander de Backer, Rony Swennen, Filip Vandelook, Bart Panis, Mario Amalfi, Cony Decock, Sofia I. F. Gomes, Vincent S. F. T. Merckx, Steven B. Janssens.)

At the end of the dry season, March and April in Southeast Asia (SEA), agricultural refuse burnings occur over the region, mainly in the countries of Myanmar, Thailand, Laos, Cambodia and Vietnam, in preparation for the wet rice plantation. In this study, the impact of biomass burnings at the height of the burning period in March 2019 in mainland SEA on air quality and pollutant transport is modelled using the Weather Research Forecast WRF-Chem air quality model with emission input from the National Center for Atmospheric Research (NCAR) Fire Emission Inventory from NCAR (FINN). FINN is derived from satellite remote sensing data and species emission factors. A simulation of the dispersion of pollutants from biomass burnings from 13 to 19 March 2019, when the burnings was most intense, was performed. Validation of the model prediction using observed meteorological and pollutant data such as AOD measurements on ground from AERONET (Aerosol Robotic Network) and data from MODIS and CALIPSO satellites is carried out at various sites in the region. The results show that impact on air quality was most pronounced in Thailand and Laos but the effect of biomass burnings in mainland SEA at the end of the dry season is widespread in terms of pollutant dispersion and population exposure over the whole region and beyond. It is also shown that the transport of pollutants from biomass burnings in SEA to southern China, Taiwan and beyond is facilitated by the Truong Son mountain range, when under westerly wind, acting as a launching pad to uplift the pollutant plumes to higher altitude which then can be dispersed widely and transported farther from the biomass burning sources in Thailand and Laos., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The burden of metabolic syndrome (MetS) has increased worldwide, especially during the COVID-19 pandemic, and this phenomenon is related to environmental, dietary, and lifestyle risk factors. We aimed to determine the association between the levels of serum heavy metals, hs-CRP, vitamins, and curry intake and to predict risks of MetS based on marginal effects. A data set of 60,256 Koreans aged ≥ 15 years between 2009 and 2017 was used to obtain information on sociodemographic, lifestyle, family history characteristics, MetS, food intake survey, and serum heavy metals. Daily intake of vitamins was measured by a one-day 24 h recall, and curry consumption was calculated using a food frequency questionnaire. Serum heavy metal levels were quantified by graphite furnace atomic absorption spectrometry and using a mercury analyzer. We found that vitamin B1, B2, B3, C, and A intakes were significantly lower in subjects with than without MetS. In contrast, serum levels of Pb, Hg, Cd, vitamin A, E, and hs-CRP were significantly higher in subjects with MetS. The risk of MetS was significantly lower for high curry consumers than low curry consumers (adjusted odds ratio 0.85, 95%CI 0.74-0.98). The risks of MetS were reduced by 12% and 1%, when vitamin B1 and C intakes increased by one mg, respectively, but were increased by 14%, 3%, and 9%, when serum levels of Pb, Hg, and hs-CRP increased by one unit. These results show that the potential health benefits resulting from vitamin and curry intakes could protect the public against the dual burden of communicable and non-communicable diseases. Further studies are required to reduce risk factors associated with serum heavy metal levels and to determine whether interactions between vitamin and curry consumption influence the presence of MetS.

The present study aimed to determine thiamine intake levels and the association between thiamine intake, diabetes, cardiovascular diseases and mental health. Participants were interviewed to obtain data on socio-demographic characteristics, lifestyle, current medications, medical and family history. The daily intake of thiamine was assessed by a 24-h recall. The mean age of the 34 700 study subjects was 42⋅9 years (sd 22⋅8, min-max: 1-80) and 19 342 (55⋅7 %) were women. The levels of thiamine intake were 1⋅126 mg (2016), 1⋅115 mg (2017) and 1⋅087 mg (2018) for women, which were equal to or only slightly above the recommended intake of 1⋅10 mg/d for women. The levels of thiamine intake from 2014-15 and 2016-18 significantly decreased. The estimated percentage of insufficient thiamine intake was 37⋅8 % (95 % CI 37⋅3, 38⋅4). Multivariable regression analysis adjusted for potential confounders showed that thiamine intake was critically associated with lower risks of hypertension, MI or angina, type 2 diabetes, depression and dyslipidemia. The daily thiamine intake from food can reversal the risks of hypertension (OR 0⋅95; 95 % CI 0⋅90, 0⋅99), MI or angina (OR 0⋅84; 95 % CI 0⋅74, 0⋅95), type 2 diabetes (OR 0⋅86; 95 % CI 0⋅81, 0⋅93), depression (OR 0⋅90; 95 % CI 0⋅83, 0⋅97) and dyslipidemia (OR 0⋅90; 95 % CI 0⋅86, 0⋅95), respectively. Further works are needed to identify the effects of thiamine and non-communicable diseases (NCDs) and mental health. A preventive thiamine supplementation strategy should be adopted to target NCDs and mental health and risk factors associated with thiamine deficiency. The optimisation of NCD control and mental health protection is also a vital integral part of Korea's public health system., (© The Author(s) 2021.)

Polycomb group (PcG) proteins repress master regulators of development and differentiation through organization of chromatin structure. Mutation and dysregulation of PcG genes cause developmental defects and cancer. PcG proteins form condensates in the cell nucleus, and these condensates are the physical sites of PcG-targeted gene silencing via formation of facultative heterochromatin. However, the physiochemical principles underlying the formation of PcG condensates remain unknown, and their determination could shed light on how these condensates compact chromatin. Using fluorescence live-cell imaging, we observed that the Polycomb repressive complex 1 (PRC1) protein chromobox 2 (CBX2), a member of the CBX protein family, undergoes phase separation to form condensates and that the CBX2 condensates exhibit liquid-like properties. Using site-directed mutagenesis, we demonstrated that the conserved residues of CBX2 within the intrinsically disordered region (IDR), which is the region for compaction of chromatin in vitro , promote the condensate formation both in vitro and in vivo We showed that the CBX2 condensates concentrate DNA and nucleosomes. Using genetic engineering, we report that trimethylation of Lys-27 at histone H3 (H3K27me3), a marker of heterochromatin formation produced by PRC2, had minimal effects on the CBX2 condensate formation. We further demonstrated that the CBX2 condensate formation does not require CBX2-PRC1 subunits; however, the condensate formation of CBX2-PRC1 subunits depends on CBX2, suggesting a mechanism underlying the assembly of CBX2-PRC1 condensates. In summary, our results reveal that PcG condensates assemble through liquid-liquid phase separation (LLPS) and suggest that phase-separated condensates can organize PcG-bound chromatin., (© 2019 Tatavosian et al.)

Environmental monitoring and modelling, especially in the regional context, has seen significant progress with the widely usage of satellite measurement in conjunction with local meteorological and air quality monitoring to understand the atmospheric dispersion and transport of air pollutants. This paper studies the application of these data and modelling tools to understand the environment effects of a major bushfire period in the state of New South Wales (NSW), Australia, in 2013. The bushfires have caused high pollution episodes at many sites in the greater Sydney metropolitan areas. The potential long-range transport of aerosols produced by bushfires to other region and states has been seen by regulators as a major concern. Using data and images collected from satellites, in addition to the results obtained from different simulations carried out using HYSPLIT trajectory model and a regional meteorological model called Conformal Cubic Atmospheric Model (CCAM), we were able to identify at least 2 days on which the smoke aerosols from bush fires in NSW has been transported at high altitude to the northern state of Queensland and the Coral Sea. As a result, widespread high particle concentration in South East Queensland including the Brisbane area, as measured by nearly all the air quality monitoring stations in this region, occurred on the day when the smoke aerosols intruded to lower altitude as indicated by the CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) Lidar measurements on the CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation) satellite. The use of meteorological or air quality modelling to connect the ground-based measurements with satellite observations as shown in this study is useful to understand the pollutant transport due to bushfires and its impact on regional air quality.

Over 80% of diffuse intrinsic pontine gliomas (DIPGs) harbor a point mutation in histone H3.3 where lysine 27 is substituted with methionine (H3.3K27M); however, how the mutation affects kinetics and function of PcG proteins remains elusive. We demonstrate that H3.3K27M prolongs the residence time and search time of Ezh2, but has no effect on its fraction bound to chromatin. In contrast, H3.3K27M has no effect on the residence time of Cbx7, but prolongs its search time and decreases its fraction bound to chromatin. We show that increasing expression of Cbx7 inhibits the proliferation of DIPG cells and prolongs its residence time. Our results highlight that the residence time of PcG proteins directly correlates with their functions and the search time of PcG proteins is critical for regulating their genomic occupancy. Together, our data provide mechanisms in which the cancer-causing histone mutation alters the binding and search dynamics of epigenetic complexes.

HaloTag has been widely used to label proteins in vitro and in vivo (Los et al ., 2008). In this protocol, we describe labelling HaloTag-Cbx fusion proteins by HaloTag ligands for live-cell single-molecule imaging (Zhen et al ., 2016).

The Polycomb PRC1 plays essential roles in development and disease pathogenesis. Targeting of PRC1 to chromatin is thought to be mediated by the Cbx family proteins (Cbx2/4/6/7/8) binding to histone H3 with a K27me3 modification (H3K27me3). Despite this prevailing view, the molecular mechanisms of targeting remain poorly understood. Here, by combining live-cell single-molecule tracking (SMT) and genetic engineering, we reveal that H3K27me3 contributes significantly to the targeting of Cbx7 and Cbx8 to chromatin, but less to Cbx2, Cbx4, and Cbx6. Genetic disruption of the complex formation of PRC1 facilitates the targeting of Cbx7 to chromatin. Biochemical analyses uncover that the CD and AT-hook-like (ATL) motif of Cbx7 constitute a functional DNA-binding unit. Live-cell SMT of Cbx7 mutants demonstrates that Cbx7 is targeted to chromatin by co-recognizing of H3K27me3 and DNA. Our data suggest a novel hierarchical cooperation mechanism by which histone modifications and DNA coordinate to target chromatin regulatory complexes., Competing Interests: JBG: Filed patent application on the Janelia Fluor (JF) dyes (PCT/US2015/023953). LDL: Filed patent application on the Janelia Fluor (JF) dyes (PCT/US2015/023953). The other authors declare that no competing interests exist.

During the dry season, from November to April, agricultural biomass burning and forest fires especially from March to late April in mainland Southeast Asian countries of Myanmar, Thailand, Laos and Vietnam frequently cause severe particulate pollution not only in the local areas but also across the whole region and beyond due to the prevailing meteorological conditions. Recently, the BASE-ASIA (Biomass-burning Aerosols in South East Asia: Smoke Impact Assessment) and 7-SEAS (7-South-East Asian Studies) studies have provided detailed analysis and important understandings of the transport of pollutants, in particular, the aerosols and their characteristics across the region due to biomass burning in Southeast Asia (SEA). Following these studies, in this paper, we study the transport of particulate air pollution across the peninsular region of SEA and beyond during the March 2014 burning period using meteorological modelling approach and available ground-based and satellite measurements to ascertain the extent of the aerosol pollution and transport in the region of this particular event. The results show that the air pollutants from SEA biomass burning in March 2014 were transported at high altitude to southern China, Hong Kong, Taiwan and beyond as has been highlighted in the BASE-ASIA and 7-SEAS studies. There are strong evidences that the biomass burning in SEA especially in mid-March 2014 has not only caused widespread high particle pollution in Thailand (especially the northern region where most of the fires occurred) but also impacted on the air quality in Hong Kong as measured at the ground-based stations and in LulinC (Taiwan) where a remote background monitoring station is located.

Epigenetic complexes play an essential role in regulating chromatin structure, but information about their assembly stoichiometry on chromatin within cells is poorly understood. The cellular assembly stoichiometry is critical for appreciating the initiation, propagation, and maintenance of epigenetic inheritance during normal development and in cancer. By combining genetic engineering, chromatin biochemistry, and single-molecule fluorescence imaging, we developed a novel and sensitive approach termed single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) to enable investigation of the cellular assembly stoichiometry of epigenetic complexes on chromatin. Sm-ChIPi was validated by using chromatin complexes with known stoichiometry. The stoichiometry of subunits within a polycomb complex and the assembly stoichiometry of polycomb complexes on chromatin have been extensively studied but reached divergent views. Moreover, the cellular assembly stoichiometry of polycomb complexes on chromatin remains unexplored. Using Sm-ChIPi, we demonstrated that within mouse embryonic stem cells, one polycomb repressive complex (PRC) 1 associates with multiple nucleosomes, whereas two PRC2s can bind to a single nucleosome. Furthermore, we obtained direct physical evidence that the nucleoplasmic PRC1 is monomeric, whereas PRC2 can dimerize in the nucleoplasm. We showed that ES cell differentiation induces selective alteration of the assembly stoichiometry of Cbx2 on chromatin but not other PRC1 components. We additionally showed that the PRC2-mediated trimethylation of H3K27 is not required for the assembly stoichiometry of PRC1 on chromatin. Thus, these findings uncover that PRC1 and PRC2 employ distinct mechanisms to assemble on chromatin, and the novel Sm-ChIPi technique could provide single-molecule insight into other epigenetic complexes., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Polycomb group (PcG) proteins are epigenetic transcriptional factors that repress key developmental regulators and maintain cellular identity through mitosis via a poorly understood mechanism. Using quantitative live-cell imaging in mouse ES cells and tumor cells, we demonstrate that, although Polycomb repressive complex (PRC) 1 proteins (Cbx-family proteins, Ring1b, Mel18, and Phc1) exhibit variable capacities of association with mitotic chromosomes, Cbx2 overwhelmingly binds to mitotic chromosomes. The recruitment of Cbx2 to mitotic chromosomes is independent of PRC1 or PRC2, and Cbx2 is needed to recruit PRC1 complex to mitotic chromosomes. Quantitative fluorescence recovery after photobleaching analysis indicates that PRC1 proteins rapidly exchange at interphasic chromatin. On entry into mitosis, Cbx2, Ring1b, Mel18, and Phc1 proteins become immobilized at mitotic chromosomes, whereas other Cbx-family proteins dynamically bind to mitotic chromosomes. Depletion of PRC1 or PRC2 protein has no effect on the immobilization of Cbx2 on mitotic chromosomes. We find that the N-terminus of Cbx2 is needed for its recruitment to mitotic chromosomes, whereas the C-terminus is required for its immobilization. Thus these results provide fundamental insights into the molecular mechanisms of epigenetic inheritance., (© 2014 Zhen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Objective: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation of molar pregnancies we measured the concentrations of free hCG beta-subunit (free hCGbeta), "total" hCG (hCG+hCGbeta) and ITA, and determined whether ITA, the two other hCG analytes, or the calculated ratios of hCGbeta/hCG+hCGbeta, hCGbeta/ITA and hCG+hCGbeta/ITA could predict the later development of PTD., Design: A retrospective study based on blood specimens collected in the Dutch Central Registry for Hydatidiform Moles. The study group comprised 97 patients with hydatidiform moles who did not develop PTD after mole evacuation and 33 patients who did develop PTD., Methods: Serum samples from 130 patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free hCGbeta, total hCG, and ITA. From these analytes we also calculated the ratios hCGbeta/hCG+hCGbeta, hCGbeta/ITA, and hCG+hCGbeta/ITA. To predict the development of PTD from these analytes and parameters we performed receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curve (AUCs) that represented the diagnostic accuracy which was rated in a range from excellent (AUC >0.9 or <0.1) to poor (AUC 0.4-0.6)., Results: The diagnostic accuracy of ITA was moderate (0.618) and not different from that of free hCGbeta (0.610) and hCG+hCGbeta (0.622)., Conclusions: ITA as well as the other analytes and parameters in serum taken prior to evacuation from patients with molar pregnancies cannot be used to predict the subsequent development of persistent trophoblastic disease.

The authors report the case of a 50 year old man with pseudowanthoma elastica with a history of myocardial infarction and severe aortic regurgitation. Angiography showed multiple coronary artery aneurysms and aneurysmal dilatation of the aortic annulus. The outcome after triple coronary bypass surgery with aortic valve replacement in a valved Bentall conduit was favourable. Pseudoxanthoma elastica is a rare condition in which the prognosis depends on the degree of vascular involvement. In this context, coronary artery aneurysms and aneurysmal dilatation of the aorta are rare complications.

The pharmacokinetics of antineoplastic drugs based on compartmental models are combined with deterministic exponential growth models of tumors containing drug-resistant and sensitive cells. Model predictions for single-drug therapy are compared with in vivo data obtained by other investigators for L1210 t-cell leukemia in mice treated with BCNU and Ara-C and for in vitro treatment of L1210 with Ara-C. The model and data compare favorably in terms of rate of tumor growth and duration of drug action for both constant infusion and bolus delivery of the drugs.