Formation of porous membranes for drug delivery systems

Highly crystalline porous hollow poly (-lactide) (PLLA) fibres suitable for the delivery of various drugs were obtained using a dry-wet spinning process. The pore structure of the fibres could be regulated by changing the spinning systems and spinning conditions. Using the spinning system PLLA-dioxane-water, fibres with a dense toplayer and a spongy sublayer were obtained. The spinning system PLLA-chloroform/toluene-methanol yielded fibres with a very open porous structure. The membrane formation of the former system probably occurs by liquid-liquid demixing followed by crystallization of the polymer rich phase. In the membrane formation process of the spinning system, PLLA-chloroform/toluene-methanol crystallization probably plays a dominant role. The membrane formation process will be related to basic principles of phase separation. The fibres are suitable for the long term zero order delivery of the contraceptive 3-ketodesogestrel and the short term zero order delivery of the cytostatic agent, cisplatin. The drugs are released by dissolution of the drug crystals in the fibre core followed by diffusion through the membrane structure. Short term release of adriamycin could be obtained through an adsorption-desorption mechanism. The pore structures of the fibres have a large influence on the release rates of the drugs investigated. When fibres with dense toplayers were used, low release rates of drugs were observed whereas fibres with well interconnected pore structures over the fibre wall showed very high release rates

Does virulence assessment of Vibrio anguillarum using sea bass (Dicentrarchus labrax) larvae correspond with genotypic and phenotypic characterization?

Background: Vibriosis is one of the most ubiquitous fish diseases caused by bacteria belonging to the genus Vibrio such as Vibrio (Listonella) anguillarum. Despite a lot of research efforts, the virulence factors and mechanism of V. anguillarum are still insufficiently known, in part because of the lack of standardized virulence assays. Methodology/Principal Findings: We investigated and compared the virulence of 15 V. anguillarum strains obtained from different hosts or non-host niches using a standardized gnotobiotic bioassay with European sea bass (Dicentrarchus labrax L.) larvae as model hosts. In addition, to assess potential relationships between virulence and genotypic and phenotypic characteristics, the strains were characterized by random amplified polymorphic DNA (RAPD) and repetitive extragenic palindromic PCR (rep-PCR) analyses, as well as by phenotypic analyses using Biolog's Phenotype MicroArray (TM) technology and some virulence factor assays. Conclusions/Significance: Virulence testing revealed ten virulent and five avirulent strains. While some relation could be established between serotype, genotype and phenotype, no relation was found between virulence and genotypic or phenotypic characteristics, illustrating the complexity of V. anguillarum virulence. Moreover, the standardized gnotobiotic system used in this study has proven its strength as a model to assess and compare the virulence of different V. anguillarum strains in vivo. In this way, the bioassay contributes to the study of mechanisms underlying virulence in V. anguillarum

Oxygen saturation targets for children with respiratory distress:a systematic review

BACKGROUND: In children with respiratory distress, supplemental oxygen is indicated at peripheral oxygen saturation ( S pO 2 ) thresholds of 90-94%. However, these thresholds are poorly studied. We conducted a systematic review to summarise the existing evidence for S pO 2 thresholds in children with respiratory distress. METHODS: Electronic databases and registries were searched for original articles published from 1 January 2010 to 7 January 2022 comparing two or more S pO 2 thresholds in children with respiratory distress. Primary outcomes were safety, including mortality, neurocognitive outcomes and readmissions, and effectiveness, including admission rate and length of hospital stay. Methodological appraisal was performed using the Cochrane Risk of Bias 2 (RoB-2) or Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) tools. Results were narratively synthesised. RESULTS: We retrieved 3384 results; seven studies were included. Lower thresholds ranged from 80% to 92% and were compared with higher thresholds ranging from 92% to 94%. Studies were highly heterogeneous in setting, design, population and outcomes. Risk of bias varied from low to high. Lower S pO 2 thresholds had equivalent mortality, neurocognitive outcomes and readmissions or re-attendance to healthcare to higher thresholds. Lower S pO 2 thresholds showed a significant decrease in admission rates by up to 40% and shortened hospitalisation duration by 10-18 h. CONCLUSIONS: The current S pO 2 thresholds of 90-94% in children with respiratory distress may be too high, which could lead to unnecessary hospitalisations and prolonged hospitalisation duration. S pO 2 thresholds as low as 88% are potentially safe in children with respiratory distress and may reduce hospitalisation rates and length of stay. However, high-quality evidence is needed to support this. </p

Chromosome-scale genome assemblies of aphids reveal extensively rearranged autosomes and long-term conservation of the X chromosome

Chromosome rearrangements are arguably the most dramatic type of mutations, often leading to rapid evolution and speciation. However, chromosome dynamics have only been studied at the sequence level in a small number of model systems. In insects, Diptera and Lepidoptera have conserved genome structure at the scale of whole chromosomes or chromosome arms. Whether this reflects the diversity of insect genome evolution is questionable given that many species exhibit rapid karyotype evolution. Here, we investigate chromosome evolution in aphids-an important group of hemipteran plant pests-using newly generated chromosome-scale genome assemblies of the green peach aphid (Myzus persicae) and the pea aphid (Acyrthosiphon pisum), and a previously published assembly of the corn-leaf aphid (Rhopalosiphum maidis). We find that aphid autosomes have undergone dramatic reorganization over the last 30 My, to the extent that chromosome homology cannot be determined between aphids from the tribes Macrosiphini (Myzus persicae and Acyrthosiphon pisum) and Aphidini (Rhopalosiphum maidis). In contrast, gene content of the aphid sex (X) chromosome remained unchanged despite rapid sequence evolution, low gene expression, and high transposable element load. To test whether rapid evolution of genome structure is a hallmark of Hemiptera, we compared our aphid assemblies with chromosome-scale assemblies of two blood-feeding Hemiptera (Rhodnius prolixus and Triatoma rubrofasciata). Despite being more diverged, the blood-feeding hemipterans have conserved synteny. The exceptional rate of structural evolution of aphid autosomes renders them an important emerging model system for studying the role of large-scale genome rearrangements in evolution

Single cell epigenetic visualization assay

Abstract Characterization of the epigenetic status of individual cells remains a challenge. Current sequencing approaches have limited coverage, and it is difficult to assign an epigenetic status to the transcription state of individual gene alleles in the same cell. To address these limitations, a targeted microscopy-based epigenetic visualization assay (EVA) was developed for detection and quantification of epigenetic marks at genes of interest in single cells. The assay is based on an in situ biochemical reaction between an antibody-conjugated alkaline phosphatase bound to the epigenetic mark of interest, and a 5′-phosphorylated fluorophore-labeled DNA oligo tethered to a target gene by gene-specific oligonucleotides. When the epigenetic mark is present at the gene, phosphate group removal by the phosphatase protects the oligo from λ-exonuclease activity providing a quantitative fluorescent readout. We applied EVA to measure 5-methylcytosine (5mC) and H3K9Ac levels at different genes and the HIV-1 provirus in human cell lines. To link epigenetic marks to gene transcription, EVA was combined with RNA-FISH. Higher 5mC levels at the silenced compared to transcribed XIST gene alleles in female somatic cells validated this approach and demonstrated that EVA can be used to relate epigenetic marks to the transcription status of individual gene alleles.</jats:p

Tiger reefs: Self-organized regular patterns in deep-sea cold-water coral reefs

Abstract Complexity theory predicts that self-organized, regularly patterned ecosystems store more biomass and are more resilient than spatially uniform systems. Self-organized ecosystems are well-known from the terrestrial realm, with “tiger bushes” being the archetypical example and mussel beds and tropical coral reefs the marine examples. We here identify regular spatial patterns in cold-water coral reefs (nicknamed “tiger reefs”) from video transects and argue that these are likely the result of self-organization. We used variograms and Lomb–Scargle analysis of seven annotated video transects to analyze spatial patterns in live coral and dead coral (i.e., skeletal remains) cover at the Logachev coral mound province (NE Atlantic Ocean) and found regular spatial patterns with length scales between 62 and 523 m in live and dead coral distribution along these transects that point to self-organization of cold-water coral reefs. Self-organization theory shows that self-organized ecosystems can withstand large environmental changes by adjusting their spatial configuration. We found indications that cold-water corals can similarly adjust their spatial configuration, possibly providing resilience in the face of climate change. Dead coral framework remains in the environment for extended periods of time, providing a template for spatial patterns that facilitates live coral recovery. The notion of regular spatial patterns in cold-water coral reefs is interesting for cold-water coral restoration, as transplantation will be more successful when it follows the patterns that are naturally present. This finding also underlines that anthropogenic effects such as ocean acidification and bottom trawling that destroy the dead coral template undermine cold-water coral resilience. Differences in the pattern periodicities of live and dead coral cover further present an interesting new angle to investigate past and present environmental conditions in cold-water coral reefs

Tiger reefs: Self‐organized regular patterns in deep‐sea cold‐water coral reefs

Complexity theory predicts that self-organized, regularly patterned ecosystems store more biomass and are more resilient than spatially uniform systems. Self-organized ecosystems are well-known from the terrestrial realm, with “tiger bushes” being the archetypical example and mussel beds and tropical coral reefs the marine examples. We here identify regular spatial patterns in cold-water coral reefs (nicknamed “tiger reefs”) from video transects and argue that these are likely the result of self-organization. We used variograms and Lomb–Scargle analysis of seven annotated video transects to analyze spatial patterns in live coral and dead coral (i.e., skeletal remains) cover at the Logachev coral mound province (NE Atlantic Ocean) and found regular spatial patterns with length scales between 62 and 523 m in live and dead coral distribution along these transects that point to self-organization of cold-water coral reefs. Self-organization theory shows that self-organized ecosystems can withstand large environmental changes by adjusting their spatial configuration. We found indications that cold-water corals can similarly adjust their spatial configuration, possibly providing resilience in the face of climate change. Dead coral framework remains in the environment for extended periods of time, providing a template for spatial patterns that facilitates live coral recovery. The notion of regular spatial patterns in cold-water coral reefs is interesting for cold-water coral restoration, as transplantation will be more successful when it follows the patterns that are naturally present. This finding also underlines that anthropogenic effects such as ocean acidification and bottom trawling that destroy the dead coral template undermine cold-water coral resilience. Differences in the pattern periodicities of live and dead coral cover further present an interesting new angle to investigate past and present environmental conditions in cold-water coral reefs

Spin Fluctuation Induced Dephasing in a Mesoscopic Ring

We investigate the persistent current in a hybrid Aharonov-Bohm ring - quantum dot system coupled to a reservoir which provides spin fluctuations. It is shown that the spin exchange interaction between the quantum dot and the reservoir induces dephasing in the absence of direct charge transfer. We demonstrate an anomalous nature of this spin-fluctuation induced dephasing which tends to enhance the persistent current. We explain our result in terms of the separation of the spin from the charge degree of freedom. The nature of the spin fluctuation induced dephasing is analyzed in detail.Comment: 4 pages, 4 figure

Incorporation of a high potential quinone reveals that electron transfer in Photosystem I becomes highly asymmetric at low temperature

Photosystem I (PS I) has two nearly identical branches of electron-transfer co-factors. Based on point mutation studies, there is general agreement that both branches are active at ambient temperature but that the majority of electron-transfer events occur in the A-branch. At low temperature, reversible electron transfer between P700 and A1A occurs in the A-branch. However, it has been postulated that irreversible electron transfer from P700 through A1B to the terminal iron-sulfur clusters FA and FB occurs via the B-branch. Thus, to study the directionality of electron transfer at low temperature, electron transfer to the iron-sulfur clusters must be blocked. Because the geometries of the donor–acceptor radical pairs formed by electron transfer in the A- and B-branch differ, they have different spin-polarized EPR spectra and echo- modulation decay curves. Hence, time-resolved, multiple-frequency EPR spectroscopy, both in the direct-detection and pulse mode, can be used to probe the use of the two branches if electron transfer to the iron-sulfur clusters is blocked. Here, we use the PS I variant from the menB deletion mutant strain of Synechocyctis sp. PCC 6803, which is unable to synthesize phylloquinone, to incorporate 2,3-dichloro-1,4-naphthoquinone (Cl2NQ) into the A1A and A1B binding sites. The reduction midpoint potential of Cl2NQ is approximately 400 mV more positive than that of phylloquinone and is unable to transfer electrons to the iron-sulfur clusters. In contrast to previous studies, in which the iron-sulfur clusters were chemically reduced and/or point mutations were used to prevent electron transfer past the quinones, we find no evidence for radical-pair formation in the B-branch. The implications of this result for the directionality of electron transfer in PS I are discussed

Active Surveillance for Papillary Thyroid Microcarcinoma in a Population with Restrictive Diagnostic Workup Strategies

Background: The worldwide incidence of papillary thyroid carcinoma (PTC) has increased. Efforts to reduce overtreatment follow two approaches: limiting diagnostic workup of low-risk thyroid nodules and pursuing active surveillance (AS) after diagnosis of microscopic PTC (mPTC). However, most studies on AS have been performed in countries with a relatively high proportion of overdiagnosis and thus incidental mPTC. The role of AS in a population with a restrictive diagnostic workup protocol for imaging and fine-needle aspiration remains unknown. Therefore, the aim of this study was to describe the proportion and characteristics of patients with mPTC in the Netherlands and to describe the potential candidates for AS in a situation with restrictive diagnostic protocols since 2007. Methods: All operated patients with an mPTC in the Netherlands between 2005 and 2015 were identified from the Netherlands Cancer Registry database. Three groups were defined: (Group 1) mPTC with preoperative distant or lymph node metastases, (Group 2) mPTC in pathology report after thyroid surgery for another indication, and (Group 3) patients with a preoperative high suspicious thyroid nodule or proven mPTC (Bethesda 5 or 6). Only patients in Group 3 were considered potential candidates for AS. Results: A total of 1018 mPTC patients were identified. Group 1 consisted of 152 patients with preoperatively discovered metastases. Group 2 consisted of 667 patients, of whom 16 (2.4%) had lymph node metastases. There were 199 patients in Group 3, of whom 27 (13.6%) had lymph node metastases. After initial treatment in Group 3, 3.5% (7/199) of the patients had recurrence. Conclusions: Restrictive diagnostic workup strategies of patients with small thyroid nodules lead to limited patients eligible for AS and a higher incidence of lymph node metastases. We believe that there is limited additive value for AS in countries with restrictive diagnostic workup guidelines such as in the Netherlands. However, if an mPTC is encountered, AS can be offered on an individual basis