To develop a screening tool to optimise neonatal drug prescription, which is often based on low-quality evidence.

Neonatal pharmacotherapy recommendations were identified by literature review and synthesised into NeoCheck tool statements. In a two-round modified Delphi process, experts from Swiss neonatal intensive care units (NICUs) rated their agreement with individual statements using a five-point Likert scale (5 = totally agree). Statements with >65% scores ≥4 in round 1 and >75% scores ≥4 in round 2 were selected.

We identified 1375 clinical guidelines via literature review. After synthesis, 158 statements were submitted to 23 experts (1 clinical pharmacist, 22 neonatologists; 65% with >10 years neonatology practice) from 10 Swiss NICUs. Nineteen items did not reach the agreement threshold and were eliminated in the second Delphi round. The final NeoCheck tool comprises 141 statements in 11 medical domains concerning 49 neonatal diseases. Most (79%) statements conscription-screening tool developed to optimise neonatal pharmacotherapy. In a future prospective study, its effect on NICU prescription optimisation and the quality of care will be assessed.

Mortality rates of COVID-19 patients hospitalised in intensive care units (ICUs) are generally high. Availability of ICU resources might influence clinical outcomes. The aim of this study was to examine the clinical course of the 42 patients treated during the first epidemic wave between 2 March and 20 May 2020 at the tertiary ICU of the Bern University Hospital, where staffing, equipment and drugs were not limited.

For this descriptive study, retrospective data of the first COVID-19 wave in an interdisciplinary adult ICU of a Swiss University hospital was used. The study included data regarding healthcare staffing and COVID-19 patients. The primary outcome was the ICU mortality in COVID-19 patients.

Patients’ median age was 61 years (range 32–86), simplified acute physiology score (SAPS-II) was 46 (13–90), 81% of the patients were males, 79% were mechanically ventilated (3 of them on extracorporeal membrane oxygenation), 31% were under renal replacement therapy and 21% recing steroids in selected cases, combined with an interdisciplinary approach and provision of sufficient human resources, were associated with low ICU and hospital mortality rates despite high disease severity. Availability of qualified human resources may have an important impact on the outcome of COVID-19.

Prompt linkage to human immunodeficiency virus (HIV) care after diagnosis is of utmost importance for individual health and reduction of HIV transmission. Different definitions for “linkage to care” have challenged comparisons as a public health marker. Its meaning in the era of “universal test and treat” has transformed in all settings, but is most relevant in sub-Sahara Africa, where the burden of new HIV infection is still highest.

For this narrative review on “linkage to care” definitions with a focus on sub-Saharan Africa, we searched PubMed/Medline between September and December 2020, restricted to the period 2000–2020 using Boolean operators “HIV” AND (“linkage to care” OR “engagement in care”) and screened for institutional definitions of “linkage to care”. Additionally, as one example of a rural sub-Saharan African setting, we analysed linkage stepsca.Experimental methods that capture the individual properties of single cells are revealing the key role of cell-to-cell variability in countless biological processes. These single-cell methods are becoming increasingly important across the life sciences in fields such as immunology, regenerative medicine and cancer biology. In addition to high-dimensional transcriptomic techniques such as single-cell RNA sequencing, there is a need for fast, simple and high-throughput assays to enumerate cell samples based on RNA biomarkers. In this work, we present single-cell nucleic acid profiling in droplets (SNAPD) to analyze sets of transcriptional markers in tens of thousands of single mammalian cells. Individual cells are encapsulated in aqueous droplets on a microfluidic chip and the RNA markers in each cell are amplified. Molecular logic circuits then integrate these amplicons to categorize cells based on the transcriptional markers and produce a detectable fluorescence output. SNAPD is capable of analyzing over 100,000 cells per hour and can be used to quantify distinct cell types within heterogeneous populations, detect rare cells at frequencies down to 0.1% and enrich specific cell types using microfluidic sorting. SNAPD provides a simple, rapid, low cost and scalable approach to study complex phenotypes in heterogeneous cell populations.The sequence-specific recognition of duplex DNA by unmodified parallel triplex-forming oligonucleotides is restricted to low pH conditions due to a necessity for cytosine protonation in the third strand. This has severely restricted their use as gene-targeting agents, as well as for the detection and/or functionalisation of synthetic or genomic DNA. Here I report that the nucleobase 6-amino-5-nitropyridin-2-one (Z) finally overcomes this constraint by acting as an uncharged mimic of protonated cytosine. Synthetic TFOs containing the nucleobase enabled stable and selective triplex formation at oligopurine-oligopyrimidine sequences containing multiple isolated or contiguous GC base pairs at neutral pH and above. see more Moreover, I demonstrate a universal strategy for the enzymatic assembly of Z-containing TFOs using its commercially available deoxyribonucleotide triphosphate. These findings seek to improve not only the recognition properties of TFOs but also the cost and/or expertise associated with their chemical syntheses.Microsatellite expansions are the cause of >20 neurological or developmental human disorders. Shortening expanded repeats using specific DNA endonucleases may be envisioned as a gene editing approach. Here, we measured the efficacy of several CRISPR-Cas nucleases to induce recombination within disease-related microsatellites, in Saccharomyces cerevisiae. Broad variations in nuclease performances were detected on all repeat tracts. Wild-type Streptococcus pyogenes Cas9 (SpCas9) was more efficient than Staphylococcus aureus Cas9 on all repeats tested, except (CAG)33. Cas12a (Cpf1) was the most efficient on GAA trinucleotide repeats, whereas GC-rich repeats were more efficiently cut by SpCas9. The main genetic factor underlying Cas efficacy was the propensity of the recognition part of the sgRNA to form a stable secondary structure, independently of its structural part. This suggests that such structures form in vivo and interfere with sgRNA metabolism. The yeast genome contains 221 natural CAG/CTG and GAA/CTT trinucleotide repeats.