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Recent studies show that using computational algorithms to design genome editing reagents can mitigate off-target edits in plants. Finally, crops are subject to strong selection to eliminate off-type plants through well-established multigenerational breeding, selection, and commercial variety development practices. Within this context, off-target edits in crops present no new safety concerns compared to other breeding practices. The current generation of genome editing technologies is already proving useful to develop new plant varieties with consumer and farmer benefits. Genome editing will likely undergo improved editing specificity along with new developments in SDN delivery and increasing genomic characterization, further improving reagent design and application.Tremor is the most common movement disorder worldwide, but diagnosis is challenging. In 2018, the task force on tremor of the International Parkinson and Movement Disorder Society published a consensus statement that proposes a tremor classification along two independent axes a clinical tremor syndrome and its underlying aetiology. In line with this statement, we here propose a stepwise diagnostic approach that leads to the correct clinical and aetiological classification of upper limb tremor. We also describe the typical clinical signs of each clinical tremor syndrome. https://www.selleckchem.com/peptide/dulaglutide.html A key feature of our algorithm is the distinction between isolated and combined tremor syndromes, in which tremor is accompanied by bradykinesia, cerebellar signs, dystonia, peripheral neuropathy or brainstem signs. This distinction subsequently informs the selection of appropriate diagnostic tests, such as neurophysiology, laboratory testing, structural and dopaminergic imaging and genetic testing. We highlight treatable metabolic causes of tremor, as well as drugs and toxins that can provoke tremor. The stepwise approach facilitates appropriate diagnostic testing and avoids unnecessary investigations. We expect that the approach offered in this article will reduce diagnostic uncertainty and increase the diagnostic yield in patients with tremor.During the Covid-19 pandemic, a strategy to minimise face-to-face (FtF) visits and limit viral spread is essential. Video consultations offer clinical assessment despite restricted movement of people.We undertook a rapid literature review to identify the highest currently available level of evidence to inform this major change in clinical practice. We present a narrative synthesis of the one international and one national guideline and two systematic reviews-all published within the last 18 months.The global evidence appears to support video consultations as an effective, accessible, acceptable and cost-effective method of service delivery. Organisations must ensure software is simple, effective, reliable and safe, with the highest level of security for confidentiality.Although video consultations cannot fully replace FtF, they can radically reduce the need for FtF and the risk of Covid-19 spread in our communities while maintaining high standards of care. For patient safety, it will be critical to follow the WHO guidance regarding a standard operating procedure; clinical protocols for when video consultations can (and cannot) be used; policies to ensure equity of access in disadvantaged populations; adequate staff training; and administrative support to coordinate appointments.The wide prevalence and regulated expression of long non-coding RNAs (lncRNAs) highlight their functional roles, but the molecular basis for their activity and structure-function relationships remain to be investigated, with few exceptions. Among the relatively few lncRNAs conserved over significant evolutionary distances is the long intergenic non-coding RNA (lincRNA) Cyrano (orthologous to human OIP5-AS1), which contains a region of 300 highly conserved nucleotides within tetrapods, which in turn contains a functional stretch of 26 nucleotides of deep conservation. This region binds to and facilitates the degradation of the microRNA miR-7, a short ncRNA with multiple cellular functions, including modulation of oncogenic expression. We probed the secondary structure of Cyrano in vitro and in cells using chemical and enzymatic probing, and validated the results using comparative sequence analysis. At the center of the functional core of Cyrano is a cloverleaf structure maintained over the >400 million years of divergent evolution that separate fish and primates. This strikingly conserved motif provides interaction sites for several RNA-binding proteins and masks a conserved recognition site for miR-7. Conservation in this region strongly suggests that the function of Cyrano depends on the formation of this RNA structure, which could modulate the rate and efficiency of degradation of miR-7.Introduction Antimicrobial resistance is rising, largely due to the indiscriminate use of antimicrobials. The human gut is the largest reservoir of antibiotic resistant bacteria (ARB). Individuals colonised with ARB have the potential to spread these organisms both in the community and hospital settings. Infections with ARB such as extended spectrum beta-lactamase producing enterobacteriales (ESBL-E) and carbapenemase producing enterobacteriales (CPE) are more difficult to treat and are associated with an increased morbidity and mortality. Presently, there is no effective decolonisation strategy for these ARB. Faecal microbiota transplant (FMT) has emerged as a potential strategy for decolonisation of ARB from the human gut, however there is significant uncertainty about the feasibility, effectiveness and safety of using this approach. Methods and analysis Prospective, randomised, patient-blinded, placebo-controlled feasibility trial of FMT to eradicate gastrointestinal carriage of ARB. Eighty patients with a recent history of invasive infection secondary to ESBL-E or CPE and persistent gastrointestinal carriage will be randomised 11 to receive encapsulated FMT or placebo. The primary outcome measure is consent rate (as a proportion of patients who fulfil inclusion/exclusion criteria); this will be used to determine if a substantive trial is feasible. Participants will be followed up at 1 week, 1 month, 3 months and 6 months and monitored for adverse events as well as gastrointestinal carriage rates of ARB after intervention. Ethics and dissemination Research ethics approval was obtained by London-City and East Research Ethics Committee (ref 20/LO/0117). Trial results will be published in a peer-reviewed journal and presented at international conferences. Trial registration number ISRCTN registration number 34 467 677 and EudraCT number 2019-001618-41.

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