Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells

Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments.United States. National Institutes of Health (DE-013023)United States. National Institutes of Health (DC-007174)United States. National Institutes of Health (DC-013909)United States. National Institutes of Health (RR-00168

Human Neurobrucellosis with Intracerebral Granuloma Caused by a Marine Mammal Brucella spp.

We present the first report of community-acquired human infections with marine mammal–associated Brucella spp. and describe the identification of these strains in two patients with neurobrucellosis and intracerebral granulomas. The identification of these isolates as marine mammal strains was based on omp2a sequence and amplification of the region flanking bp26

Proteomic Insights into the Hidden World of Phloem Sap Feeding

The physical interface between a phloem-feeding insect and its host plant is a single cell buried deep within the plant tissue. As such, the molecular interactions between these notorious agricultural pests and the crop plants upon which they feed are diffi cult to study. ‘Omic’ technologies have proved crucial in revealing some of the fascinating detail of the molecular interplay between these partners. Here we review the role of proteomics in identifying putative components of the secreted saliva of phloem-feeding insects, particularly aphids, and discuss the limited knowledge concerning the function of these proteins

A multisite longitudinal evaluation of patient characteristics associated with a poor response to non-surgical multidisciplinary management of low back pain in an advanced practice physiotherapist-led tertiary service

Background: Non-surgical multidisciplinary management is often the first pathway of care for patients with chronic low back pain (LBP). This study explores if patient characteristics recorded at the initial service examination have an association with a poor response to this pathway of care in an advanced practice physiotherapist-led tertiary service. Methods: Two hundred and forty nine patients undergoing non-surgical multidisciplinary management for their LBP across 8 tertiary public hospitals in Queensland, Australia participated in this prospective longitudinal study. Generalised linear models (logistic family) examined the relationship between patient characteristics and a poor response at 6 months follow-up using a Global Rating of Change measure. Results: Overall 79 of the 178 (44%) patients completing the Global Rating of Change measure (28.5% loss to follow-up) reported a poor outcome. Patient characteristics retained in the final model associated with a poor response included lower Formal Education Level (ie did not complete school) (Odds Ratio (OR (95% confidence interval)) (2.67 (1.17–6.09), p = 0.02) and higher self-reported back disability (measured with the Oswestry Disability Index) (OR 1.33 (1.01–1.77) per 10/100 point score increase, p = 0.046). Conclusions: A low level of formal education and high level of self-reported back disability may be associated with a poor response to non-surgical multidisciplinary management of LBP in tertiary care. Patients with these characteristics may need greater assistance with regard to their comprehension of health information, and judicious monitoring of their response to facilitate timely alternative care if no benefits are attained.</p

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Contributions from the DISC to accomplish the Aeolus mission objectives

The Aeolus Data Innovation and Science Cluster (DISC) supports the Aeolus mission with a wide range of activities from instrument and product quality monitoring over retrieval algorithm improvements to numerical weather prediction (NWP) impact assessments for wind and aerosols. The Aeolus DISC provides support to ESA, Cal/Val teams, numerical weather prediction (NWP) centers, and scientific users for instrument special operations and calibration, for the re-processing of Aeolus products from the past and through the provision of bi-annual updates of the L1A, L1B, L2A and L2B operational processors. The Aeolus DISC is coordinated by DLR with partners from ECMWF, KNMI, Météo-France, TROPOS, DoRIT, ABB, s&t, serco, OLA, Physics Solutions, IB Reissig and Les Myriades involving more than 40 scientists and engineers. The presentation will highlight the Aeolus DISC activities with a focus for the year 2021 and early 2022 since the last Aeolus workshop in November 2020. This covers the evolution of the instrument performance including investigations of the cause of the on-going signal loss and the achieved improvement via dedicated laser tests in 2021. In addition, refinements of algorithms and correction of the wind bias will be discussed - including a known remaining seasonal bias in October and March as encountered during the re-processing campaigns. Finally, the strategy for the on-going and future re-processing campaigns will be addressed to inform the scientific community about the availability and quality of the re-processed data products. The Aeolus mission has fully achieved its mission objectives including the unprecedented demonstration of direct-detection Doppler wind lidar technology and high-power laser operation in space in the ultraviolet spectral region over its planned full mission lifetime of 3 years and 3 months. Aeolus wind products have clearly demonstrated positive impact on forecasts using several NWP models. Since early 2020, and thus only 1.5 years after launch, the Aeolus wind products are used in operation at various NWP centers worldwide. This was achieved even despite the larger than expected wind random errors due to lower initial atmospheric signal levels and the observed signal losses during the operation of the first and second laser. In addition to this incredible success, first scientific studies demonstrated the use of Aeolus for atmospheric dynamics research in the stratosphere and for the analysis of aerosol transport. These achievements of the Aeolus mission and its success were only possible with the essential and critical contributions from the Aeolus DISC. This demonstrates the need and potential for setting up such scientific consortia covering a wide range of expertise from instrument, processors, and scientific use of products for Earth Explorer type missions. The invaluable experience gained by the Aeolus DISC during the more then 3 years of Aeolus mission in orbit (preceded by a period of 20 years before launch by a similar study team) is a pre-requisite for a successful preparation of an operational follow-on Aeolus-2 mission