The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination.

The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination-the regeneration of myelin sheaths-also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota.This work was supported by grants from UK Multiple Sclerosis Society, The British Trust for the Myelin Project, MedImmune, The Adelson Medical Research Foundation, Wellcome Trust, BBSRC, the Leverhulme Trust and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute. CEM was supported by grants from the Jean Shanks Foundation and the James Baird Fund, AGF was supported by an ECTRIMS fellowship and OBZ received a BIRAX fellowship

Achieving benchmarks for national quality indicators reduces recurrence and progression in non-muscle-invasive bladder cancer

Background Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non–muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland’s National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. Objective To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. Design, setting, and participants QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. Intervention QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). Outcome measurements and statistical analysis The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. Key findings and limitations Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6–9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4–24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73–0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59–0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45–0.84, p = 0.002 and HR 0.65, 95% CI = 0.49–0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. Conclusions Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. Patient summary Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non–muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression

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

Photographic representation of skin tones in three dermatology journals.

Although ethnic diversity is rising in the United States, educational resources continue to lag behind, as evidenced by prior studies highlighting limited skin of color representation in dermatology resources. The objective of this study was to evaluate the representation of skin tones in three dermatology journals commonly used in resident education and journal clubs. Overall, 5.6% (Journal of the American Academy of Dermatology), 4.1% (JAMA Dermatology), and 8.3% (Pediatric Dermatology) of images in the journals were depicted on Dark skin (Fitzpatrick V-VI). Disparities in skin of color representation exist in three dermatology journals used in medical education in the United States