Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various ...countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low‐risk GTN (FIGO Stages I–III: score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN (FIGO Stages II–III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.
Gestational trophoblastic disease, although rare, needs special attention because if managed properly, likelihood of cure is almost 100%.
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•Microplastic abundance and distribution were characterized in NE Pacific seawater samples.•Microplastic particles (62–5000μm) were found in seawater at all stations.•Microplastic ...concentrations were highest nearshore, consistent with land-based sources.•Low microplastic levels SW of Vancouver Island are consistent with La Perouse Bank upwelling.•This assessment provides a basis to evaluate the in-coming debris from Tohoku Tsunami.
We document the abundance, composition and distribution of microplastics in sub-surface seawaters of the northeastern Pacific Ocean and coastal British Columbia. Samples were acid-digested and plastics were characterized using light microscopy by type (fibres or fragments) and size (<100, 100–500, 500–100 and >1000μm). Microplastics concentrations ranged from 8 to 9200particles/m3; lowest concentrations were in offshore Pacific waters, and increased 6, 12 and 27-fold in west coast Vancouver Island, Strait of Georgia, and Queen Charlotte Sound, respectively. Fibres accounted for ∼75% of particles on average, although nearshore samples had more fibre content than offshore (p<0.05). While elevated microplastic concentrations near urban areas are consistent with land-based sources, the high levels in Queen Charlotte Sound appeared to be the result of oceanographic conditions that trap and concentrate debris. This assessment of microplastics in the NE Pacific is of interest in light of the on-coming debris from the 2011 Tohoku Tsunami.
Gestational trophoblastic disease Seckl, Michael J, Prof; Sebire, Neil J, FRCPath; Berkowitz, Ross S, MD
The Lancet (British edition),
08/2010, Letnik:
376, Številka:
9742
Journal Article
Recenzirano
Summary Gestational trophoblastic disease encompasses a range of pregnancy-related disorders, consisting of the premalignant disorders of complete and partial hydatidiform mole, and the malignant ...disorders of invasive mole, choriocarcinoma, and the rare placental-site trophoblastic tumour. These malignant forms are termed gestational trophoblastic tumours or neoplasia. Improvements in management and follow-up protocols mean that overall cure rates can exceed 98% with fertility retention, whereas most women would have died from malignant disease 60 years ago. This success can be explained by the development of effective treatments, the use of human chorionic gonadotropin as a biomarker, and centralisation of care. We summarise strategies for management of gestational trophoblastic disease and address some of the controversies and future research directions.
Municipal wastewater treatment plants (WWTPs) are conduits through which microplastics (MPs) are released into aquatic environments. However, the technical challenges in working with wastewater ...sample matrices have precluded reliable particle count budget calculations. We applied newly-adapted methods for MP collection and analysis to a study of a major WWTP serving a population of 1.3 million people near Vancouver, Canada. Suspected MP particles, including fibres, were counted and categorized using light microscopy in influent, primary effluent, secondary effluent, primary sludge and secondary sludge. Fourier Transform Infrared Spectroscopy (FT-IR) confirmed that just 32.4% of the suspected MPs were plastic polymers. Using FT-IR corrected data, we estimate that 1.76 ± 0.31 trillion MPs enter the WWTP annually, with 1.28 ± 0.54 trillion MPs settling into primary sludge, 0.36 ± 0.22 into secondary sludge, and 0.03 ± 0.01 trillion MPs released into the receiving environment. This corresponds to a retention of microplastics of up to 99% in the WWTP.
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•Wastewater treatment plants release microplastics into aquatic environments.•An estimated 1.76 trillion microplastics per year enter a major urban WWTP in Vancouver.•98% of microplastics entering the WWTP were retained in solids, 70% being fibres.•With 30 billion particles released to the ocean, there exist concerns about risk to biota.
The high storage capacities and excellent biocompatibilities of metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. Incorporation of surface functionality is ...a route to enhanced properties, and here we report on a surface-modification procedure—click modulation—that controls their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1) synthesized as ∼200 nm nanoparticles coated with functionalized modulators, (2) loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol) (PEG) chains through mild bioconjugate reactions. At pH 7.4, the PEG chains endow the MOF with enhanced stability toward phosphates and overcome the “burst release” phenomenon by blocking interaction with the exterior of the nanoparticles, whereas at pH 5.5, stimuli-responsive drug release is achieved. The mode of cellular internalization is also tuned by nanoparticle surface chemistry, such that PEGylated UiO-66 potentially escapes lysosomal degradation through enhanced caveolae-mediated uptake. This makes it a highly promising vector, as demonstrated for dichloroacetic-acid-loaded materials, which exhibit enhanced cytotoxicity. The versatility of the click modulation protocol will allow a wide range of MOFs to be easily surface functionalized for a number of applications.
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•A surface modification protocol for MOFs compatible with cargo loading is reported•PEGylated UiO-66 nanoparticles show pH-responsive cargo release•Endocytosis routes are modified by the control of MOF surface chemistry•Enhanced cytotoxicity is observed for PEGylated UiO-66 loaded with dichloroacetate
Using artificial agents to deliver drugs selectively to sites of disease while protecting them from metabolism and clearance offers potential routes to new treatments. Porous metal-organic frameworks (MOFs) have emerged as potential candidates because they offer high storage capacities and easy clearance after delivery. We report on a method that controls the size and surface chemistry of MOFs and is compatible with cargo loading, showing that surface modification with biocompatible poly(ethylene glycol) chains improves stability toward phosphate and allows pH-responsive cargo release, which could enhance selectivity because cancerous cells are typically more acidic than healthy ones. Modes of cellular uptake are also altered, which could account for the enhanced cell death when polymer-coated MOFs are loaded with the anticancer drug dichloroacetic acid. Surface modification is mild and could be applied across a range of MOFs, opening up applications in selective molecular separation, blending into hybrids, and turn-on catalysis.
Porous nanoparticles that can store drug molecules have great potential in drug delivery, the use of nanocarriers to transport therapeutic agents around the body. Forgan and colleagues report on a method that controls the surface properties and functionality of metal-organic framework nanoparticles to enhance their stability, allow stimuli-responsive release of drug molecules, and enhance the anticancer therapeutic effect of loaded drugs by changing the route of cell uptake. Further development of these materials could enhance drug efficiencies and avoid unwanted side effects.
Abstract Placental site (PSTT) and epithelioid trophoblastic tumor (ETT) are rare types of gestational trophoblastic neoplasia (GTN) that arise from intermediate trophoblast. Given that this cell of ...origin is different from other forms of GTN, it is not surprising that the clinical presentation, tumor marker profile, and treatment paradigm for PSTT and ETT are quite different as well. The mainstay for therapy for stage I PSTT and ETT is hysterectomy with adjuvant chemotherapy reserved for those presenting greater than four years from the antecedent pregnancy. Surgery is also important for metastatic disease. There is no standardized chemotherapy regimen for advanced stage disease but often consists of a platinum-containing combination therapy, usually EMA-EP or TE/TP. Despite its rarity, PSTT and ETT account for a disproportionate percentage of mortality from GTN likely resulting from their relative chemotherapy resistance. Novel therapeutic modalities therefore are needed to improve the outcomes of women with advanced stage or resistant PSTT and ETT.
Heterojunctions between three-dimensional (3D) semiconductors with different bandgaps are the basis of modern light-emitting diodes, diode lasers and high-speed transistors. Creating analogous ...heterojunctions between different 2D semiconductors would enable band engineering within the 2D plane and open up new realms in materials science, device physics and engineering. Here we demonstrate that seamless high-quality in-plane heterojunctions can be grown between the 2D monolayer semiconductors MoSe2 and WSe2. The junctions, grown by lateral heteroepitaxy using physical vapour transport, are visible in an optical microscope and show enhanced photoluminescence. Atomically resolved transmission electron microscopy reveals that their structure is an undistorted honeycomb lattice in which substitution of one transition metal by another occurs across the interface. The growth of such lateral junctions will allow new device functionalities, such as in-plane transistors and diodes, to be integrated within a single atomically thin layer.
Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient ...preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition.
The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group.
Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded.
One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.
Conformational changes of linker units in metal‐organic frameworks (MOFs) are often responsible for gate‐opening phenomena in selective gas adsorption and stimuli‐responsive optical and electrical ...sensing behaviour. Herein, we show that pressure‐induced bathochromic shifts in both fluorescence emission and UV/Vis absorption spectra of a two‐fold interpenetrated Hf MOF, linked by 1,4‐phenylene‐bis(4‐ethynylbenzoate) ligands (Hf‐peb), are induced by rotation of the central phenyl ring of the linker, from a coplanar arrangement to a twisted, previously unseen conformer. Single‐crystal X‐ray diffraction, alongside in situ fluorescence and UV/Vis absorption spectroscopies, measured up to 2.1 GPa in a diamond anvil cell on single crystals, are in excellent agreement, correlating linker rotation with modulation of emission. Topologically isolating the 1,4‐phenylene‐bis(4‐ethynylbenzoate) units within a MOF facilitates concurrent structural and spectroscopic studies in the absence of intermolecular perturbation, allowing characterisation of the luminescence properties of a high‐energy, twisted conformation of the previously well‐studied chromophore. We expect the unique environment provided by network solids, and the capability of combining crystallographic and spectroscopic analysis, will greatly enhance understanding of luminescent molecules and lead to the development of novel sensors and adsorbents.
Pressure‐induced bathochromic shifts in both fluorescence emission and UV/Vis absorption spectra of a two‐fold interpenetrated Hf MOF are induced by rotation of the central phenyl ring of the linker. Single‐crystal X‐ray diffraction was measured up to 2.1 GPa, thus correlating linker rotation with modulation of emission.
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