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Purpose In this work, we tested the hypothesis that microneedles provide a minimally invasive method to inject particles into the suprachoroidal space for drug delivery to the back of the eye. Methods A single, hollow microneedle was inserted into the sclera, and infused nanoparticle and microparticle suspensions into the suprachoroidal space. Experiments were performed on whole rabbit, pig, and human eyes ex vivo. Particle delivery was imaged using brightfield and fluorescence microscopy as well as microcomputed tomography. Results Microneedles were shown to deliver sulforhodamine B as well as nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig, and human eyes. Volumes up to 35 μL were administered consistently. Optimization of the delivery device parameters showed that microneedle length, pressure, and particle size played an important role in determining successful delivery into the suprachoroidal space. Needle lengths of 800-1,000 μm and applied pressures of 250-300 kPa provided most reliable delivery. Conclusions Microneedles were shown for the first time to deliver nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig and human eyes. This shows that microneedles may provide a minimally invasive method for controlled drug delivery to the back of the eye.

In this work, we investigated the emerging pollutants in Taiwanese groundwater for the first time and correlated their presence with possible contamination sources. Fifty target pharmaceuticals and perfluorinated chemicals in groundwater were mostly present at ng L −1 concentrations, except for 17α-ethynylestradiol, sulfamethoxazole, and acetaminophen (maximums of 1822, 1820, and 1036 ng L −1 , respectively). Perfluorinated compounds were detected with the highest frequencies in groundwater at almost all of the sample sites, especially short-chained perfluorinated carboxylates, which were easily transferred to the groundwater. The results indicate that the compounds found to have high detection frequencies and concentrations in groundwater are similar to those found in other countries around the world. Most common pharmaceuticals that contain hydrophilic groups, such as sulfonamide antibiotics and caffeine, are easily transported through surface waters to groundwater. The results also indicated that the persistent natures of emerging contaminants with high detection frequencies in surface water and groundwater, such as perfluorooctanesulfonate (risk quotient >1), caffeine, and carbamazepine, should be further studied and evaluated.

Understanding biological systems and mimicking their functions require electronic tools that can interact with biological tissues with matched softness. These tools involve biointerfacing materials that should concurrently match the softness of biological tissue and exhibit suitable electrical conductivities for recording and reading bioelectronic signals. However, commonly employed intrinsically soft and stretchable materials usually contain solvents that limit stability for long-term use or possess low electronic conductivity. To date, an ultrasoft (i.e., Young’s modulus <30 kPa), conductive, and solvent-free elastomer does not exist. Additionally, integrating such ultrasoft and conductive materials into electronic devices is poorly explored. This article reports a solvent-free, ultrasoft and conductive PDMS bottlebrush elastomer (BBE) composite with single-wall carbon nanotubes (SWCNTs) as conductive fillers. The conductive SWCNT/BBE with a filler concentration of 0.4 − 0.6 wt% reveals an ultralow Young’s modulus (<11 kPa) and satisfactory conductivity (>2 S/m) as well as adhesion property. Furthermore, we fabricate ultrasoft electronics based on laser cutting and 3D printing of conductive and non-conductive BBEs and demonstrate their potential applications in wearable sensing, soft robotics, and electrophysiological recording. Conductive materials with tissue-matched softness are needed for ultra-soft electronics. Here, the authors report ultra-soft and conductive bottlebrush elastomer composites and fabricate them into electronics with laser cutting and 3D printing methods.

Many lipophilic pharmaceuticals may be sorbed in solid phases, leading to different photochemical behaviors. This study investigated the photochemistry of ciprofloxacin in a solid-phase system and compared it to that in a water-phase system. Kaolinite was used as the model solid matrix. The photolysis of ciprofloxacin in kaolinite fits pseudo-first-order kinetics for thicknesses less than 199 μm, and the rate constants k p decreased from 0.0154 to 0.0016 min −1 as the thickness of the layer increased. Unlike the aqueous phase, two-step degradation processes were observed for all kaolinite layer thicknesses (14–199 μm), and the pseudo-first-order constant at the surface of the kaolinite layer was smaller than that in the water phase. Comparatively , a similar photolysis rate constant of ciprofloxacin in a kaolinite suspension was also observed, and it was an order of magnitude smaller than that of the direct photodegradation (0.035 min −1 ) in water. The results indicate that ciprofloxacin is likely more stable when it is adsorbed on kaolinite and that the half-lives of ciprofloxacin in kaolinite and a kaolinite suspension are 2–25 times longer than that in deionized water (20 min) under simulated sunlight. Direct photolysis is proposed to be the main photodegradation mechanism for ciprofloxacin in kaolinite, and the cleavage of a piperazine ring is the main degradation pathway. However, the interaction between ciprofloxacin and kaolinite reduces the direct photolysis and leads to a higher light stability. In association with the reduction in photolysis, the yields of norfloxacin and defluorinated byproduct decreased significantly. Consequently, the interaction increases the persistence of ciprofloxacin and thus the ecological risk to the environment.

This study aimed to perform a preliminary screen of various waters for pollution by emerging contaminants and identifying potential cross-contamination problems in aquaculture systems. Specifically, the occurrence and distribution of 110 emerging contaminants (49 antibiotics, 49 other pharmaceuticals, and 12 industrial/household compounds) in 14 aquaculture sites (fish, shrimp, and shellfish ponds) and three surrounding aquatic environments in Taiwan were investigated. All the detected compounds were at nanogram per liter to sub-microgram per liter levels. Six pharmaceuticals that occurred at high concentrations and frequencies were ibuprofen (788 ng/L), lincomycin (624 ng/L), flumequine (331 ng/L), caffeine (276 ng/L), ifosfamide (220 ng/L), and cephalexin (172 ng/L). Other commonly detected emerging contaminants (with detection frequencies > 70%) were sulfamethoxazole, erythromycin-H2O, atenolol, methadone, benzotriazole, tolyltriazole, perfluorobutane sulfonate (PFBS), perfluoroheptanoic acid (PFHpA), perfluorooctanoate (PFOA), and perfluorononanoic acid (PFNA). This work demonstrated the impact of aquaculture activities (i.e., usage of antibiotics) on the surrounding aquatic environments and, at the same time, how the surrounding anthropogenic activities impact aquaculture waters. Cross-contamination was observed between these two aquatic systems; emerging contaminants resulting from human activities, such as perfluorinated chemicals, anticorrosive substances, and anticancer and abused drugs, from the surrounding waters were found to be introduced into the aquaculture systems.

Benzotriazole (BT) and 5-methyl-1H-benzotriazole (5-MeBT) are broadly used in industrial applications, such as anti-icing fluids and dishwashing detergent, and act as the primary building blocks for UV absorbers and photostabilizers. This study examined the occurrence of these two compounds in the environment and their unique photochemical behavior affecting photosensitizers and other micro-organic pollutants in aqueous environments. BT and 5-MeBT were detected in all river water samples from the major rivers in Taipei City in the concentration ranges of 147 to 1560 ng/L and 22 to 235 ng/L, respectively, and both compounds persisted through a conventional wastewater treatment plant. The direct photolysis half-lives of BT and 5-MeBT were 56.9 and 14.0 h, respectively. The half-life of photolysis in river water for BT was 44.2 h, whereas the half-life of 5-MeBT was 24.7 h. The long half-lives in real-water matrices resulted in their prevalence in water bodies, and these compounds were also found to minimize the photosensitizing ability of nitrate and dissolved organic matter (DOM) and increase the persistence of other micro-organic pollutant. With BT present, the production of · OH in nitrate photolysis was reduced, the degradation of DOM under sunlight was hindered, and the photodegradation of pharmaceutical residues in surface water, such as methotrexate, was completely impeded. This study suggests that in cases in which BT and 5-MeBT are highly concentrated, the effectiveness of natural attenuation process, i.e., photodegradation, in the aqueous environment is diminished, which increases the persistence of the pollutants as well as the risk of exposure.

Costello syndrome (OMIM# 218040) is a distinctive rare multisystem disorder comprising a characteristic coarse facial appearance, intellectual disabilities, and tumor predisposition. Although the diagnosis can be suspected clinically, confirmation requires identification of a heterozygous mutation in the proto-oncogene HRAS . In contrast to somatic oncogenic mutations in neoplasia, the Costello syndrome changes are typically introduced in the paternal germline. The predicted amino acid substitutions allow for constitutive or prolonged activation of the HRAS protein, resulting in dysregulation of the Ras/mitogen activated protein kinase pathway. Dysregulation of this signaling pathway is the disease mechanism shared among Costello syndrome and other rasopathies, including neurofibromatosis type 1, Noonan syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. The Ras/mitogen activated protein kinase pathway governs cell proliferation and differentiation, and its dysregulation affects cardiac and brain development, accounting for the significant overlap in physical and developmental differences and common medical problems among rasopathies. Unlike the genetically heterogeneous Noonan syndrome and cardio-facio-cutaneous syndrome, Costello syndrome is caused by HRAS mutations only. Patients, clinicians, and researchers may benefit from a multidisciplinary “rasopathy clinic,” which serves patients with more common conditions such as Noonan syndrome and neurofibromatosis and those affected by rare conditions such as Costello syndrome. Genet Med 2012:14(3):285–292

We investigated the ozonation of the antineoplastic drugs cyclophosphamide (CP), ifosfamide (IF), and 5-fluorouracil (5-FU) and of the vasodilator pentoxifylline (PEN) in distilled water, in pharmaceutical wastewater, and in hospital effluent at pH 5–11. Under an alkaline pH of 11, all of the target compounds rapidly degraded through the attack of hydroxyl radicals, which resulted in their complete removal within 5 min at an ozone supply rate of 3 g O₃/h. Under acidic pH conditions, such as pH 5.6, CP and IF exhibited slower removal rates; however, compounds with unsaturated C-C bonds, such as 5-FU and PEN, were still removed at rapid rates under acidic conditions. Although the parent compounds were removed within minutes, the resulting ozonation byproducts were resistant to further ozonation and possessed increased Microtox acute toxicity. In distilled water, the resulting ozonation products exhibited minimal mineralization but high acute toxicity, whereas in naturally buffered pharmaceutical and hospital effluents, the byproducts were more amenable to removal and detoxification.

Seadragons are a remarkable lineage of teleost fishes in the family Syngnathidae, renowned for having evolved male pregnancy. Comprising three known species, seadragons are widely recognized and admired for their fantastical body forms and coloration, and their specific habitat requirements have made them flagship representatives for marine conservation and natural history interests. Until recently, a gap has been the lack of significant genomic resources for seadragons.We have produced gene-annotated, chromosome- scale genome models for the leafy and weedy seadragon to advance investigations of evolutionary innovation and elaboration of morphological traits in seadragons as well as their pipefish and seahorse relatives. We identified several interesting features specific to seadragon genomes, including divergent noncoding regions near a developmental gene important for integumentary outgrowth, a high genome-wide density of repetitive DNA, and recent expansions of transposable elements and a vesicular trafficking gene family. Surprisingly, comparative analyses leveraging the seadragon genomes and additional syngnathid and outgroup genomes revealed striking, syngnathid-specific losses in the family of fibroblast growth factors (FGFs), which likely involve reorganization of highly conserved gene regulatory networks in ways that have not previously been documented in natural populations. The resources presented here serve as important tools for future evolutionary studies of developmental processes in syngnathids and hold value for conservation of the extravagant seadragons and their relatives.

RASA1-related disorders are vascular malformation syndromes characterized by hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. The number of cases reported is relatively small; and while the main clinical features are CMs and AVMs/AVFs, the broader phenotypic spectrum caused by variants in the RASA1 gene is still being defined. Here, we report the clinical and molecular findings in 69 unrelated cases with a RASA1 variant identified at ARUP Laboratories. Sanger sequencing and multiplex ligation-dependent probe amplification were primarily used to evaluate RASA1. Several atypical cases were evaluated using next-generation sequencing (NGS) and array-comparative genomic hybridization (aCGH). Sixty individuals had a deleterious RASA1 variant of which 29 were novel. Nine individuals had a variant of uncertain significance. Five large RASA1 deletions were detected, giving an overall deletion/duplication rate of 8.3% (5/60) among positive cases. Most (75.4%) individuals with a RASA1 variant had CMs, and 44.9% had an AVM/AVF. Clinical findings in several cases expand the RASA1 phenotype. Our data suggest that screening for large RASA1 deletions and duplications in this disorder is important and suggest that NGS multi-gene panel testing is beneficial for the molecular diagnosis of cases with complex vascular phenotypes.