Severe Inflammation Following Vaccination Against Streptococcus pneumoniae in Patients With Cryopyrin-Associated Periodic Syndromes

OBJECTIVE: Pneumococcal vaccination is recommended for patients receiving immunosuppressive drugs. We describe unusually severe adverse reactions to pneumococcal vaccination in each of 7 consecutive patients with cryopyrin-associated periodic syndromes (CAPS). METHODS: Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines. Clinical information was collected retrospectively. RESULTS: Within a few hours after the vaccination, all 7 patients developed severe local reactions at the injection site. Two patients had to be hospitalized for systemic reactions including fever. All symptoms resolved in a period of 3–17 days. CONCLUSION: Our findings indicate that pneumococcal vaccines can trigger a severe local and systemic inflammatory reaction in patients with CAPS and possibly patients with other autoinflammatory diseases. Careful consideration is warranted when implementing current European League Against Rheumatism immunization guidelines in this patient population

Opticin: a potent anti-angiogenic/antiproliferative agent for breast cancer therapy

No abstract available

A preliminary audit of medical and aid provision in English Rugby union clubs:compliance with Regulation 9

BackgroundGoverning bodies are largely responsible for the monitoring and management of risks associated with a safe playing environment, yet adherence to regulations is currently unknown. The aim of this study was to investigate and evaluate the current status of medical personnel, facilities, and equipment in Rugby Union clubs at regional level in England.MethodsA nationwide cross-sectional survey of 242 registered clubs was undertaken, where clubs were surveyed online on their current medical personnel, facilities, and equipment provision, according to regulation 9 of the Rugby Football Union (RFU).ResultsOverall, 91 (45. 04%) surveys were returned from the successfully contacted recipients. Of the completed responses, only 23.61% (n = 17) were found to be compliant with regulations. Furthermore, 30.56% (n = 22) of clubs were unsure if their medical personnel had required qualifications; thus, compliance could not be determined. There was a significant correlation (p = −0.029, r = 0.295) between club level and numbers of practitioners. There was no significant correlation indicated between the number of practitioners/number of teams and number of practitioners/number of players. There were significant correlations found between club level and equipment score (p = 0.003, r = −0.410), club level and automated external defibrillator (AED) access (p = 0.002, r = −0.352) and practitioner level and AED access (p = 0.0001, r = 0.404). Follow-up, thematic analysis highlighted widespread club concern around funding/cost, awareness, availability of practitioners and AED training.ConclusionThe proportion of clubs not adhering overall compliance with Regulation 9 of the RFU is concerning for player welfare, and an overhaul, nationally, is required

Study protocol for First Dental Steps Intervention: feasibility study of a health visitor led infant oral health improvement programme.

BACKGROUND: Dental caries in childhood is a burden on the daily lives of children and their families, and associated with poor oral health in adulthood. In England, dental caries is the most common reason for young children to be admitted to hospital. It is believed that most tooth extractions (due to decay) for children aged 10 years and under, could be avoided with improved prevention and early management. National public health policy recommendations in England include specific oral health initiatives to tackle tooth decay. One of these initiatives is delivered as part of the Healthy Child Programme and includes providing workforce training in oral health, integrating oral health advice into home visits, and the timely provision of fluoride toothpaste. This protocol seeks to assess the delivery of the First Dental Steps intervention and uncertainties related to the acceptability, recruitment, and retention of participants. METHODS: This study seeks to explore the feasibility and acceptability of the First Dental Steps intervention and research methods. First Dental Steps intervention will be delivered in local authority areas in South West England and includes oral health training for health visitors (or community nursery nurses) working with 0-5-year-olds and their families. Further, for vulnerable families, integrating oral health advice and the provision of an oral health pack (including a free flow cup, an age appropriate toothbrush, and 1450 ppm fluoride toothpaste) during a mandated check by a health visitor. In this study five local authority areas will receive the intervention. Interviews with parents receiving the intervention and health visitors delivering the intervention will be undertaken, along with a range of additional interviews with stakeholders from both intervention and comparison sites (four additional local authority areas). DISCUSSION: This protocol was written after the start of the COVID-19 pandemic, as a result, some of the original methods were adjusted specifically to account for disruptions caused by the pandemic. Results of this study will primarily provide evidence on the acceptability and feasibility of both the First Dental Steps intervention and the research methods from the perspective of both families and stakeholders

Low frequency radio properties of the z>5 quasar population

Optically luminous quasars at z > 5 are important probes of super-massive black hole (SMBH) formation. With new and future radio facilities, the discovery of the brightest low-frequency radio sources in this epoch would be an important new probe of cosmic reionization through 21-cm absorption experiments. In this work, we systematically study the low-frequency radio properties of a sample of 115 known spectroscopically confirmed z > 5 quasars using the second data release of the Low Frequency Array (LOFAR) Two Metre Sky survey (LoTSS-DR2), reaching noise levels of ∼80 µJy beam−1 (at 144 MHz) over an area of ∼ 5720 deg2 . We find that 41 sources (36%) are detected in LoTSS-DR2 at > 2σ significance and we explore the evolution of their radio properties (power, spectral index, and radio loudness) as a function of redshift and rest-frame ultra-violet properties. We obtain a median spectral index of −0.29+0.10 −0.09 by stacking 93 quasars using LoTSS-DR2 and Faint Images of the Radio Sky at Twenty Centimetres (FIRST) data at 1.4 GHz, in line with observations of quasars at z < 3. We compare the radio loudness of the high-z quasar sample to a lower-z quasar sample at z ∼ 2 and find that the two radio loudness distributions are consistent with no evolution, although the low number of high-z quasars means that we cannot rule out weak evolution. Furthermore, we make a first order empirical estimate of the z = 6 quasar radio luminosity function, which is used to derive the expected number of high-z sources that will be detected in the completed LoTSS survey. This work highlights the fact that new deep radio observations can be a valuable tool in selecting high-z quasar candidates for follow-up spectroscopic observations by decreasing contamination of stellar dwarfs and reducing possible selection biases introduced by strict colour cuts

The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana

Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific ‘‘avirulent’’ pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NBLRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector

Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies

Introduction: Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20-year follow-ups. Methods: In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology. Cognitive performance was tested five times over 20 years. Linkage to electronic health records identified incident dementia. The results were replicated in the Atherosclerosis Risk in Communities (ARIC) study. Results: Fifteen non-amyloid/non-tau–related proteins were associated with cognitive decline and dementia, were consistently identified in both cohorts, and were not explained by known dementia risk factors. Levels of six of the proteins are modifiable by currently approved medications for other conditions. Discussion: This study identified several plasma proteins in dementia-free people that are associated with long-term risk of cognitive decline and dementia