Strongyloidiasis in a nonagenarian who previously worked in conservancy services

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Evidence-Based PET for Neurological Diseases

Over the past two decades, one of the major breakthroughs for the approach to neurological diseases both in the clinical and research settings has been represented by the validation of diagnostic biomarkers able to demonstrate the presence of pathological mechanisms, alteration in neurotransmission as well as to predict disease progression [1, 2]. The use of PET with different tracers as well as other imaging biomarkers support the etiological diagnosis of neurological disorders in vivo. This approach is particularly relevant in the field of neurodegenerative diseases. In fact, neurodegenerative diseases are characterized by the progressive degeneration and death of neurons. They represent a heterogeneous group of conditions characterized by different etiologies, different neuropathological and neurochemical alterations leading to different clinical pictures and courses [3]. Indeed, an early accurate diagnosis allows to tackle the disease with available or experimental intervention, lifestyle changes, or logistical arrangements, before disability has developed. Early intervention is expected to have greater clinical impact, extend independent and active life, improve its quality, and decrease the burden and costs of the disease [4]. However, the validation of PET tracers in neurological disease is still ongoing, and evidence on its comparative and combined diagnostic value with respect to other biomarkers is incomplete [4, 5]. As a matter of fact, the increasing pressure for cost-effectiveness requires systematic assessment and validation of all biomarker performance in the clinical settings. Similarly only an evidence-based approach to new PET tracers can allow to select the most promising tracers for PET imaging in the research field both for pathophysiological investigations and for upcoming diagnostic approaches

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Circulating MicroRNAs in Plasma as Novel Biomarkers for Alzheimer's Disease

Conference Theme: Nature and Nurture in Brain FunctionsAlzheimer’s disease (AD) is the most common and complex neurodegenerative disorder. Although it has been over a hundred years since AD was originally described, the exact underlying mechanism remains largely elusive and no curative drugs are available for AD treatment. Early diagnosis of AD is believed to be essential for effective administration of drugs targeting. However, there are still no prefect biomarkers for AD diagnosis. Recent findings suggest that microRNAs (miRNAs) in the circulating system act as potential biomarkers for AD. In the present study, we extracted total RNAs from the plasma of 12 Chinese AD patients and 6 normal controls. Eight miRNA candidates (miR-29a, -125b, -146b, let-7f, -181a, -30c, -128 and -16) were selected and their expression profiles in plasma were measured using qRT-PCR (quantitative reverse transcription polymerase chain reaction). Our data demonstrated that plasma miR-128 was significantly down-regulated in AD patients compared with control subjects. Moreover, plasma miR-128 levels significantly correlated with protein markers in cerebrospinal fluid (CSF) and Mini Mental State Examination (MMSE) scores of the subjects. Importantly, plasma miR-128 showed good accuracy to distinguish AD patients from control subjects based on receiver operating characteristic (ROC) curve analysis. In conclusion, our results indicated that miR-128 in plasma could be a potential non-invasive biomarker of AD

A "tricky" subarachnoid hemorrhage

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A highly contagious psoriasiform eruption on the scalp of a patient with systemic lupus erythematosus

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