EsxA, a type VII secretion system-dependent effector, reveals a novel function in the sporulation of Bacillus cereus ATCC14579.

BACKGROUND: Bacillus cereus is a Gram-positive, spore-forming bacterium that produces a spectrum of effectors integral to bacterial niche adaptation and the development of various infections. Among those is EsxA, whose secretion depends on the EssC component of the type VII secretion system (T7SS). EsxA's roles within the bacterial cell are poorly understood, although postulations indicate that it may be involved in sporulation. However, the T7SS repertoire in B. cereus has not been reported, and its functions are unestablished. METHODS: We used the type strain, B. cereus ATCC14579, to generate ΔessC mutant through homologous recombination using the homing endonuclease I-SceI mediated markerless gene replacement. Comparatively, we analyzed the culture supernatant of type strain and the ΔessC mutant through Liquid chromatography-tandem mass spectrometry (LC-MS/MS). We further generated T7SSb-specific gene mutations to explore the housekeeping roles of the T7SSb-dependent effectors. The sporulation process of B. cereus ATCC14579 and its mutants was observed microscopically through the classic Schaeffer-Fulton staining method. The spore viability of each strain in this study was established by enumerating the colony-forming units on LB agar. RESULTS: Through LC-MS/MS, we identified a pair of nearly identical (94%) effector proteins named EsxA belonging to the sagEsxA-like subfamily of the WXG100 protein superfamily in the culture supernatant of the wild type and none in the ΔessC mutant. Homology analysis of the T7SSb gene cluster among B. cereus strains revealed diversity from the 3' end of essC, encoding additional substrates. Deletions in esxA1 and esxA2 neither altered cellular morphology nor growth rate, but the ΔesxA1ΔesxA2 deletion resulted in significantly fewer viable spores and an overall slower sporulation process. Within 24 h culture, more than 80% of wild-type cells formed endospores compared to less than 5% in the ΔesxA1ΔesxA2 mutant. The maximum spore ratios for the wild type and ΔesxA1ΔesxA2 were 0.96 and 0.72, respectively. Altogether, these results indicated that EsxA1 and EsxA2 work cooperatively and are required for sporulation in B. cereus ATCC14567. CONCLUSION: B. cereus ATCC14579 possesses two nearly identical T7SSb-dependent effectors belonging to the sagEsxA-like proteins. Simultaneous deletion of genes encoding these effectors significantly delayed and reduced sporulation, a novel finding for EsxA.

Selpercatinib prior to radioactive iodine for pediatric papillary thyroid carcinoma.

OBJECTIVES: We introduced selpercatinib prior to radioactive iodine therapy prior to radioactive iodine therapy (RAI) for pediatric papillary thyroid cancer (PTC) to enhance the tumorical effects of RAI. CASE PRESENTATION: PTC has an excellent prognosis but is commonly associated with local and distant metastases. Successful complete response to the current standard of care, thyroidectomy with lymph node resection and RAI, is achieved in only a small minority of cases with metastases. The direct effect of tyrosine kinase inhibitors (TKIs) on tumor regression has been confirmed in several randomized controlled studies, while the increased RAI uptake has been reported in small case series, but typically TKIs are currently reserved third-line. Selpercatinib is a TKI that specifically has a durable effect in RET-fusion positive malignancies. We describe a 10-year-old Hispanic girl with metastatic PTC treated with total thyroidectomy and extensive lymph node resection. Evaluation for relevant genetic drivers of the malignancy revealed a strong overexpression of the RET tyrosine kinase domain indicative of a RET gene fusion. Selpercatinib 120 mg twice daily given orally was initiated prior to the initial dose of RAI to achieve further tumor regression by a direct cytostatic effect and then secondarily enhancement of RAI uptake. Minimal side effects occurred, specifically intermittent mild skin rashes that resolved. Resolution of distal lung metastases was noted on CT imaging. RAI was then administered 9 months afterward, with ultimately achievement of a low thyroglobulin level 1.0 ng/mL 11 months after RAI. CONCLUSIONS: In conclusion, selpercatinib given prior to the initial dose of adjunctive RAI for RET-fusion positive PTC is a well-tolerated intervention that further reduces tumor burden and potentially enhances the tumorcidal effects of RAI.

hERG channel agonist NS1643 strongly inhibits invasive astrocytoma cell line SMA-560.

Gliomas are highly malignant brain tumours that remain refractory to treatment. Treatment is typically surgical intervention followed by concomitant temozolomide and radiotherapy; however patient prognosis remains poor. Voltage gated ion channels have emerged as novel targets in cancer therapy and inhibition of a potassium selective subtype (hERG, Kv11.1) has demonstrated antitumour activity. Unfortunately blockade of hERG has been limited by cardiotoxicity, however hERG channel agonists have produced similar chemotherapeutic benefit without significant side effects. In this study, electrophysiological recordings suggest the presence of hERG channels in the anaplastic astrocytoma cell line SMA-560, and treatment with the hERG channel agonist NS1643, resulted in a significant reduction in the proliferation of SMA-560 cells. In addition, NS1643 treatment also resulted in a reduction of the secretion of matrix metalloproteinase-9 and SMA-560 cell migration. When combined with temozolomide, an additive impact was observed, suggesting that NS1643 may be a suitable adjuvant to temozolomide and limit the invasiveness of glioma.

Functional Noncentrosymmetric Nanoparticle-Nanofiber Hybrids via Selective Fragmentation.

Noncentrosymmetric nanostructures are an attractive synthetic target as they can exhibit complex interparticle interactions useful for numerous applications. However, generating uniform, colloidally stable, noncentrosymmetric nanoparticles with low aspect ratios is a significant challenge using solution self-assembly approaches. Herein, we outline the synthesis of noncentrosymmetric multiblock co-nanofibers by subsequent living crystallization-driven self-assembly of block co-polymers, spatially confined attachment of nanoparticles, and localized nanofiber fragmentation. Using this strategy, we have fabricated uniform diblock and triblock noncentrosymmetric π-conjugated nanofiber-nanoparticle hybrid structures. Additionally, in contrast to Brownian motion typical of centrosymmetric nanoparticles, we demonstrated that these noncentrosymmetric nanofibers undergo ballistic motion in the presence of H2O2 and thus could be employed as nanomotors in various applications, including drug delivery and environmental remediation.

Impacts of trace mineral source and ancillary drench on steer performance during a 60-day backgrounding phase.

Nutritional approaches to optimize cattle health and performance during the receiving period are warranted. This experiment evaluated the impacts of supplementing organic complexed Cu, Co, Mn, and Zn on productive and health responses of high-risk beef cattle during a 60-day backgrounding phase. Crossbred steers (120) were purchased at auction and transported to the experimental facility, where BW was recorded (day-1; initial shrunk BW = 227.7 ± 1.3 kg). On day 0, steers were ranked by BW and allocated to one of eight groups and housed in drylot pens equipped with GrowSafe automated feeding systems (Model 8000; two bunks/pen). Groups were randomly assigned to receive a total mixed ration containing: (1) sulfate sources of Cu, Co, Mn, and Zn (INR; n = 40); (2) organic complexed sources of the same minerals (AAC; Zinpro Availa 4 based on a metal:amino acid complex ratio of 1:1 for Zn, Cu, and Mn in addition to cobalt glucoheptonate; Zinpro Corp., Eden Prairie, MN; n = 40); or (3) AAC and an organic complexed trace mineral drench (APF; 30 mL/hd; Zinpro ProFusion, Zinpro Corp.) on day 0 and with morbidity treatment (n = 40). Diets provided the same daily amount of all nutrients and minerals based on 7 g/steer daily of Zinpro Availa 4. Steers were assessed for bovine respiratory disease (BRD) signs daily. Liver biopsies were performed on days 0, 28 and 60. Blood samples were collected on days 0, 2, 6, 10, 13, 21, 28 and 45. No treatment differences were detected (P ≥ 0.23) for feed intake, final BW, average daily gain, or BRD incidence. Mean liver Co concentrations were greater (P = 0.02) in AAC and APF compared to INR steers. Mean liver Cu was greater (P = 0.02) in APF compared to AAC steers. Liver Zn tended to be greater (P = 0.10) on day 28 but less (P = 0.05) on day 60 for INR compared to AAC and APF steers. Plasma cortisol was lowest (P = 0.05) for AAC steers on day 6, whereas AAC steers tended to have greater (P = 0.09) plasma cortisol on day 13 compared with APF. Plasma haptoglobin tended to be greater (P ≤ 0.10) for INR steers on days 28 and 45 compared to AAC and APF. While supplementing cattle with AAC or INR results in similar animal performance and clinical disease, AAC and APF reduce stress and acute phase protein responses.

Tailored Energy Funneling in Photocatalytic π-Conjugated Polymer Nanofibers for High-Performance Hydrogen Production.

The creation of artificial high-performance photosynthetic assemblies with a tailorable antenna system to deliver absorbed solar energy to a photosynthetic reaction center, thereby mimicking biological photosynthesis, remains a major challenge. We report the construction of recyclable, high-performance photosynthetic nanofibers with a crystalline π-conjugated polyfluorene core as an antenna system that funnels absorbed solar energy to spatially defined sensitized Co(II) porphyrin photocatalysts for the hydrogen evolution reaction. Highly effective energy funneling was achieved by tuning the dimensions of the nanofibers to exploit the very long exciton diffusion lengths (>200 nm) associated with the highly crystalline polyfluorene core formed using the living crystallization-driven self-assembly seeded growth method. This enabled efficient solar light-driven hydrogen production from water with a turnover number of over 450 for 8 h of irradiation, an H2 production rate of ca. 65 mmol h-1 g-1, and an overall quantum yield of 0.4% in the wavelength region (<405 nm) beyond the absorption of the molecular photocatalyst. The strategy of using a tailored antenna system based on π-conjugated polymers and maximizing exciton transport to a reaction center reported in this work opens up future opportunities for potential applications in other fields such as solar overall water splitting, CO2 reduction, and photocatalytic small molecule synthesis.

An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity.

Brain tumours have significant impacts on patients' quality of life, and current treatments have limited effectiveness. To improve understanding of tumour development and explore new therapies, researchers rely on experimental models. However, reproducing tumour-associated epilepsy (TAE) in these models has been challenging. Existing models vary from cell lines to in vivo studies, but in vivo models are resource-intensive and often fail to mimic crucial features like seizures. In this study, we developed a technique in which normal rat organotypic brain tissue is implanted with an aggressive brain tumour. This method produces a focal invasive lesion that preserves neural responsiveness and exhibits epileptiform hyperexcitability. It allows for real-time imaging of tumour growth and invasion for up to four weeks and microvolume fluid sampling analysis of different regions, including the tumour, brain parenchyma, and peritumoral areas. The tumour cells expand and infiltrate the organotypic slice, resembling in vivo behaviour. Spontaneous seizure-like events occur in the tumour slice preparation and can be induced with stimulation or high extracellular potassium. Furthermore, we assess extracellular fluid composition in various regions of interest. This technique enables live cell confocal microscopy to record real-time tumour invasion properties, whilst maintaining neural excitability, generating field potentials, and epileptiform discharges, and provides a versatile preparation for the study of major clinical problems of tumour-associated epilepsy.

How COVID-19 impacted people with disabilities: A qualitative study in Delaware.

Objectives: The COVID-19 pandemic created unprecedented challenges for people with disabilities and their caregivers and service providers. An assessment of how the COVID-19 pandemic, and the public health response to it, inequitably impacted the health and well-being of people with disabilities is needed to improve preparedness for future public health emergencies. Interviews were conducted with the goal of documenting the impacts of COVID-19 on community-dwelling individuals in Delaware. Study design: Qualitative interviews using a structured interview guide. Methods: In November and December 2022, interviews were conducted with individuals with disabilities, their caregivers, governmental and non-profit service providers, and elected representatives in Delaware. Interviews focused on obtaining information related to COVID-related threats to maintaining good health, affordable and accessible housing, work, educational opportunities, transportation, and community belonging during the pandemic. Interview transcripts were inductively analyzed. Results: Five themes were identified including changes to, or loss of, home-based medical and other services, changes in daily routines that impacted access to work and education, limits on access to transportation, financial strains and housing issues, and mental health concerns. Conclusions: The COVID-19 pandemic impacted nearly all aspects of the lives of people with disabilities. COVID-19 presented long-term, existential threats to progress made toward independent living, meaningful work, and financial, health, and educational equity for people with disabilities.

Phylogenomic analyses of Sapindales support new family relationships, rapid Mid-Cretaceous Hothouse diversification, and heterogeneous histories of gene duplication.

Sapindales is an angiosperm order of high economic and ecological value comprising nine families, c. 479 genera, and c. 6570 species. However, family and subfamily relationships in Sapindales remain unclear, making reconstruction of the order's spatio-temporal and morphological evolution difficult. In this study, we used Angiosperms353 target capture data to generate the most densely sampled phylogenetic trees of Sapindales to date, with 448 samples and c. 85% of genera represented. The percentage of paralogous loci and allele divergence was characterized across the phylogeny, which was time-calibrated using 29 rigorously assessed fossil calibrations. All families were supported as monophyletic. Two core family clades subdivide the order, the first comprising Kirkiaceae, Burseraceae, and Anacardiaceae, the second comprising Simaroubaceae, Meliaceae, and Rutaceae. Kirkiaceae is sister to Burseraceae and Anacardiaceae, and, contrary to current understanding, Simaroubaceae is sister to Meliaceae and Rutaceae. Sapindaceae is placed with Nitrariaceae and Biebersteiniaceae as sister to the core Sapindales families, but the relationships between these families remain unclear, likely due to their rapid and ancient diversification. Sapindales families emerged in rapid succession, coincident with the climatic change of the Mid-Cretaceous Hothouse event. Subfamily and tribal relationships within the major families need revision, particularly in Sapindaceae, Rutaceae and Meliaceae. Much of the difficulty in reconstructing relationships at this level may be caused by the prevalence of paralogous loci, particularly in Meliaceae and Rutaceae, that are likely indicative of ancient gene duplication events such as hybridization and polyploidization playing a role in the evolutionary history of these families. This study provides key insights into factors that may affect phylogenetic reconstructions in Sapindales across multiple scales, and provides a state-of-the-art phylogenetic framework for further research.

Plastid phylogenomics clarifies broad-level relationships in Bulbophyllum (Orchidaceae) and provides insights into range evolution of Australasian section Adelopetalum.

The hyperdiverse orchid genus Bulbophyllum is the second largest genus of flowering plants and exhibits a pantropical distribution with a center of diversity in tropical Asia. The only Bulbophyllum section with a center of diversity in Australasia is sect. Adelopetalum. However, the phylogenetic placement, interspecific relationships, and spatio-temporal evolution of this section remain largely unclear. To infer broad-level relationships within Bulbophyllum, and interspecific relationships within sect. Adelopetalum, a genome skimming dataset was generated for 89 samples, which yielded 70 plastid coding regions and a nuclear ribosomal DNA cistron. For 18 additional samples, Sanger data from two plastid loci (matK and ycf1) and nuclear ITS were added using a supermatrix approach. The study provided new insights into broad-level relationships in Bulbophyllum, including phylogenetic evidence for the non-monophyly of sections Beccariana, Brachyantha, Brachypus, Cirrhopetaloides, Cirrhopetalum, Desmosanthes, Minutissima, Oxysepala, Polymeres, and Sestochilos. Section Adelopetalum and sect. Minutissima s.s. formed a highly supported clade that was resolved as a sister group to the remainder of the genus. Divergence time estimations based on a relaxed molecular clock model placed the origin of Bulbophyllum in the Early Oligocene (ca. 33.2 Ma) and sect. Adelopetalum in the Late Oligocene (ca. 23.6 Ma). Ancestral range estimations based on a BAYAREALIKE model identified the Australian continent as the ancestral area of the sect. Adelopetalum. The section underwent crown diversification from the mid-Miocene to the late Pleistocene, predominantly in continental Australia. At least two independent long-distance dispersal events were inferred eastward from the Australian continent to New Zealand and to New Caledonia from the early Pliocene onwards, likely mediated by predominantly westerly winds of the Southern hemisphere. Retraction and fragmentation of the eastern Australian rainforests from the early Miocene onwards are likely drivers of lineage divergence within sect. Adelopetalum facilitating allopatric speciation.

Sinonasal Symptom Outcomes following Endoscopic Anterior Cranial Base Surgery in the Pediatric Population.

Objective This study aimed to evaluate the impact of endoscopic anterior cranial base (ACB) surgery on sinonasal symptoms in the pediatric population utilizing the Sino-Nasal Outcome Test (SNOT)-22 questionnaire. Design This is a retrospective review. Setting The study was conducted at a tertiary academic medical center. Participants Thirty-four consecutive patients, age 6 to 17 years, M:F 14:20, who underwent endoscopic ACB surgery from July 2008 to August 2019. Ten patients had baseline and a minimum of two subsequent postoperative SNOT-22 questionnaires available for analysis. Main Outcome Measures Baseline and postoperative SNOT-22 scores were compared. The mean change from baseline sinonasal symptom scores in the pediatric and historical adult cohorts was compared. Results The mean baseline SNOT-22 score for our 10 patient cohort was 0.46 out of 5 for each of the first 10 sinonasal-specific questions. This worsened to 1.69 at 1 month and returned to near baseline, 0.7, at 3 months postoperatively. The mean quality-of-life score improved to 0.91 at 1 month and 0.6 at 3 months postoperatively. The mean change from baseline for the following items: need to blow nose, runny nose, postnasal discharge, thick nasal discharge, wake up at night, reduced concentration, and frustrated/restless/irritable were similar to those in our historical adult cohort at 3 months postoperatively. Conclusion Endoscopic ACB surgery in the pediatric population results in increased sinonasal symptom morbidity in the early postoperative period; however, symptoms return to near baseline by ∼3 months, and quality-of-life scores progressively improve in the postoperative period. These trends were similar to those seen in our historic adult cohort.

Barriers and facilitators to targeted anxiety prevention programmes in families at risk: a qualitative interview study.

Anxiety disorders are the most common psychiatric disorder in children and young people. They can be prevented in those at risk, but families do not always take up opportunities to participate in prevention programmes. This qualitative study aimed to understand what families with children who were at prospective risk of anxiety disorders perceived to be the barriers to access to targeted anxiety prevention programmes, and to explore what would help facilitate access. We used Information Power to determine our sample size, and individually interviewed seven young people (14-17 years) who had anxiety disorders and their mothers, each of whom had pre-natal anxiety disorders. We transcribed all interviews and thematically analyzed them to identify perceived barriers and facilitators to targeted anxiety prevention programmes. Perceived potential barriers to access included possible negative consequences of anxiety prevention, difficulties in identifying anxiety as a problem and concerns about how professions would respond to raising concerns about anxiety. Possible facilitators included promoting awareness of anxiety prevention programmes and involvement of schools in promotion and delivery of prevention. Our findings illustrate that implementation of targeted anxiety prevention could be improved through (i) the provision of tools for parents to recognize anxiety in their children as a problem, (ii) promotion of awareness, as well as delivery, of anxiety prevention via schools and (iii) the involvement of parents and possibly adolescents in the intervention programme, but not younger children.

UV-filter pollution: current concerns and future prospects.

UV-filters are widely used in cosmetics and personal care products to protect users' skin from redamage caused by ultraviolet (UV) radiation from the sun. Globally, an estimated 16,000 to 25,000 tonnes of products containing UV-filters were used in 2014 with modern consumption likely to be much higher. Beyond this use in cosmetics and personal care products, UV-filters are also widely used to provide UV-stability in industrial products such as paints and plastics. This review discusses the main routes by which UV-filters enter aquatic environments and summarises the conclusions of studies from the past 10 years that have investigated the effects of UV-filters on environmentally relevant species including corals, microalgae, fish, and marine mammals. Safety data regarding the potential impact of UV-filters on human health are also discussed. Finally, we explore the challenges surrounding UV-filter removal and research on more environmentally friendly alternatives to current UV-filters.

Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

Prepubescent unilateral gynecomastia secondary to excessive soy consumption.

OBJECTIVE: We present a case of an unusual cause of prepubertal gynecomastia. CASE PRESENTATION: Enlargement of breast tissue in males, or gynecomastia, is a rare condition in prepubescent boys. We describe an 8-year-old male who developed unilateral gynecomastia secondary to marked dietary soy consumption. While the majority of cases are idiopathic, soy products, particularly those consumed by our patient, can contain high levels of phytoestrogens, which have been documented in limited case studies to contribute to abnormal development of breast tissue in adolescent and adult males. To our knowledge, this is the first documented case of gynecomastia occurring in a prepubescent patient resulting from excessive intake of dietary soy. Importantly, we also report a complete resolution of gynecomastia upon exclusion of dietary products containing significant amounts of soy. CONCLUSION: While soybeans and soy-derived products can be an important source of nutrition for some, those with abnormal sensitivity to phytoestrogens may benefit from limiting dietary soy consumption to avoid potential adverse effects, including gynecomastia.

Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer in children, adolescents and young adults.

OBJECTIVE: Recombinant human TSH (rhTSH) is commonly used to prepare patients for postoperative radioiodine (I-131) ablation after surgery for differentiated thyroid cancer (DTC). In adults, rhTSH is associated with equivalent oncologic efficacy in comparison to thyroid hormone withdrawal (THW), but its use has not been well studied in children. We aimed to measure time to disease progression after rhTSH stimulation vs. THW in paediatric patients under the age of 21 with DTC following total thyroidectomy. DESIGN: Retrospective cohort study (March 2001-July 2018). PATIENTS: Sixteen children and adolescents (75% female, median age, 17.4 years) who received rhTSH were compared to 29 historical controls (72% female, median age, 18.5 years) prepared with THW, followed for a median of 2.4 years (range, 0.5-14). MEASUREMENTS: Stimulated serum TSH concentrations prior to I-131 ablation and time to disease progression, as determined by a component outcome variable encompassing both structural and biochemical disease persistence/recurrence. RESULTS: No differences were observed in tumour characteristics and I-131 dose (median 2.3 [1.8-2.90] mCi/kg rhTSH) between groups. Patients who received rhTSH achieved a similar median stimulated TSH level (163 [127-184] mU/L), compared to those who underwent THW (136 [94.5-197] mU/L; p = .20). Both groups exhibited similar time to progression (p = .13) and disease persistence/recurrence rates (rhTSH 31% vs. THW 59%, p = .14). CONCLUSION: In this cohort of children and adolescents with DTC, we observed similar time to disease progression among those who received rhTSH or underwent THW prior to postoperative I-131 ablation.

Hyperandrogenism and malignant degeneration of hepatic adenomas in the setting of Abernethy malformation.

Abernethy malformation refer to a congenital absence of intrahepatic portal veins leading to a primarily extrahepatic congenital portosystemic shunt. The lack of intrahepatic portal veins leads to a characteristic set of physical exam and imaging findings that may include hyperandrogenism and liver masses such as hepatic adenomas or focal nodular hyperplasia. In this case report, we describe a 20-year-old female who presented with an enlarging hepatic adenoma. A separate hepatic adenoma had previously been biopsied and noted to have undergone malignant degeneration into hepatocellular carcinoma. For each lesion, she was treated with combination transarterial embolization and microwave ablation. On follow-up imaging after therapy, it was then noted that her extrahepatic portal vein drained directly into the inferior vena cava, consistent with congenital portosystemic shunt. Recognition of this vascular anomaly is critical in treatment planning, as early intervention with either medical therapy or surgery can prevent the metabolic sequela of this unique constellation of symptoms.

Early initiation of direct anticoagulation after stroke in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: The safety of early initiation of anticoagulant therapy in patients with ischaemic stroke related to atrial fibrillation (AF) is unknown. We investigated the safety of early initiation of direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs) or no anticoagulation. METHODS: This observational, retrospective, single-centre study included consecutive patients with recent (<4 weeks) ischaemic stroke and AF. The primary outcome was the rate of major (intracranial and extracranial) bleeding in patients on different treatment schemes, i.e. DOACs, VKAs and not anticoagulated. We also investigated the rate of ischaemic cerebrovascular events and mortality. RESULTS: We included 959 consecutive patients with AF and ischaemic stroke followed up for an average of 16.1 days after the index event. A total of 559 out of 959 patients (58.3%) were anticoagulated with either VKAs (n = 259) or DOACs (n = 300). Anticoagulation was started after a mean of 7 ± 9.4 days in the DOAC group and 11.9 ± 19.7 days in the VKA group. Early initiation of any anticoagulant was not associated with an increased risk of any major bleeding [odds ratio (OR), 0.49; 95% confidence intervals (CI), 0.21-1.16] and in particular of intracranial bleeding (OR, 0.47; 95% CI, 0.17-1.29; P = 0.143) compared with no anticoagulation. In contrast to VKAs (OR, 0.78; 95% CI, 0.28-2.13), treatment with DOACs (OR, 0.32; 95% CI, 0.10-0.96) reduced the rate of major bleeding compared with no anticoagulation. Early recurrences of ischaemic stroke did not differ significantly among the three groups. CONCLUSIONS: Starting DOACs within a mean of 7 days after stroke appeared to be safe. Randomized controlled studies are needed to establish the added efficacy of starting anticoagulation early after stroke.

A Smart Phosphine-Diyne Polymer Displays "Turn-On" Emission with a High Selectivity for Gold(I/III) Ions.

A polymeric phosphine sensor is reported that exhibits bright blue fluorescence in the presence of gold(I/III) ions but is nonemissive with other metal ions. Specifically, solutions of a poly(p-arylenediethynylene phosphine) copolymer are 35 or 94 times more emissive when treated with solutions of (tht)AuCl or HAuCl4·3H2O, respectively. Model compound studies confirm phosphine coordination to metals, including gold(I/III) and rhodium(I), and the selective "turn-on" fluorescence was investigated using time-dependent density functional theory calculations.