The rockefeller university

The contribution of bacterial infection to chronic low back pain and its treatment with antibiotics have generated considerable controversy in literature. If efficacious, antibiotics have the potential to transform the treatment of chronic low back pain in a significant subset of patients. Some microbiology studies of disc tissue from patients with CLBP have shown that bacteria are present, most likely due to infection, while others conclude they are absent or if found, it is due to surgical contamination. Clinical studies testing the efficacy of oral antibiotics to treat CLBP have either shown that the treatment is efficacious leading to significantly reduced pain and disability or that their effect is modest and not clinically significant. Critical review of the literature on CLBP, bacterial infection and treatment with antibiotics identified five well-designed and executed microbiology studies characterizing bacteria in disc samples that demonstrate that bacteria do infect herniated disc tissue, but that the bacterial burden is low and may be below the limits of detection in some studies. Two randomized, controlled clinical trials evaluating oral antibiotics in patients with CLBP indicate that for certain subsets of patients, the reduction in pain and disability achieved with antibiotic therapy may be significant. In patients for whom other therapies have failed, and who might otherwise progress to disc replacement or fusion surgery, antibiotic therapy may well be an attractive option to reduce the individual suffering associated with this debilitating condition. Additional clinical research is recommended to refine the selection of patients with CLBP caused or complicated by bacterial infection and most likely to respond to antibiotics, to optimize antibiotic therapy to maximize patient benefit, to minimize and manage side effects, and to address legitimate concerns about antibiotic stewardship. (C) 2021 The Author(s). Published by Elsevier Inc.

Vocal learning is the ability to imitate and modify sounds through auditory experience, a rare trait found in only a few lineages of mammals and birds. It is a critical component of human spoken language, allowing us to verbally transmit speech repertoires and knowledge across generations. In many vocal learning species, the vocal learning trait is sexually dimorphic, where it is either limited to males or present in both sexes to different degrees. In humans, recent findings have revealed subtle sexual dimorphism in vocal learning/spoken language brain regions and some associated disorders. For songbirds, where the neural mechanisms of vocal learning have been well studied, vocal learning appears to have been present in both sexes at the origin of the lineage and was then independently lost in females of some subsequent lineages. This loss is associated with an interplay between sex chromosomes and sex steroid hormones. Even in species with little dimorphism, like humans, sex chromosomes and hormones still have some influence on learned vocalizations. Here we present a brief synthesis of these studies, in the context of sex determination broadly, and identify areas of needed investigation to further understand how sex chromosomes and sex steroid hormones help establish sexually dimorphic neural structures for vocal learning.

Surface epithelia provide a critical barrier to the outside world. Upon a barrier breach, resident epithelial and immune cells coordinate efforts to control infections and heal tissue damage. Inflammation can etch lasting marks within tissues, altering features such as scope and quality of future responses. By remembering inflammatory experiences, tissues are better equipped to quickly and robustly respond to barrier breaches. Alarmingly, in disease states, memory may fuel the inflammatory fire. Here, we review the cellular communication networks in barrier tissues and the integration between tissue-resident and recruited immune cells and tissue stem cells underlying tissue adaptation to environmental stress.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of genetic disorders characterized by infections with weakly virulent environmental mycobacteria (EM) or Mycobacterium bovis bacillus Calmette-Guerin (BCG). Herein, we described the case of a 4.5-year-old boy with protein-losing enteropathy, lymphoproliferation, and candidiasis, who was found to have disseminated Mycobacterium simiae infection. A homozygous mutation in the IL12B gene, c.527_528delCT (p.S176Cfs*12) was identified, responsible for the complete IL-12p40 deficiency. He was resistant to anti-mycobacterial treatment and finally died due to sepsis-related complications.

At the start of the pandemic caused by the novel coronavirus (SARS-CoV-2), the Gaucher disease community anticipated that infection with this emerging viral pathogen would be associated with high morbidity and mortality in individuals with this chronic metabolic disorder. Surprisingly, however, preliminary studies suggest that Gaucher disease does not confer a higher risk of severe, life-threatening effects of SARS-CoV-2 infection, and no severe cases have been reported in large cohorts of patients from the United States, Europe and Israel. It is thought that the accumulation of glucocerebroside in the cells of Gaucher patients may promote immune tolerance rather than inflammation on exposure to SARS-CoV-2. We review here the current concepts of Gaucher disease and SARS-CoV-2 infection, focusing particularly on general prevention and vaccination. We also discuss the susceptibility to COVID-19 of patients with inborn errors of type 1 interferon (IFN alpha and IFN omega) immunity.

Recent advances in human naive pluripotent stem cell culture have demonstrated their ability to generate trophectoderm and descendant trophoblast cell types. Moreover, the same cells when cultured in three-dimensional configurations self-organize to generate blastocyst-like structures called blastoids. These discoveries represent a major step forward in modeling early human embryonic development.

Recent advances in synthetic human embryology has provided a previously inexistent molecular portrait of human development. Models of synthetic human embryonic tissues capitalize on the self-organizing capabilities of human embryonic stem cells when they are cultured on biomimetic conditions that simulate in vivo human development. In this Review, we discuss these models and how they have shed light on the early stages of human development including amniotic sac development, gastrulation and neurulation. We discuss the mechanisms underlying the molecular logic of embryonic tissue self-organization that have been dissected using synthetic models of human embryology and explore future challenges in the field. Geared with technological advances in bioengineering, high resolution gene expression and imaging tools, these models are set to transform our understanding of the mechanistic basis of embryonic tissue self-organization during human development and how they may go awry in disease.

Polyphasic sleep is the practice of distributing multiple short sleep episodes across the 24-hour day rather than having one major and possibly a minor (& ldquo;nap & rdquo;) sleep episode each day. While the prevalence of poly phasic sleep is unknown, anecdotal reports suggest attempts to follow this practice are common, particularly among young adults. Polyphasic-sleep advocates claim to thrive on as little as 2 hours of total sleep per day. However, significant concerns have been raised that polyphasic sleep schedules can result in health and safety consequences. We reviewed the literature to identify the impact of polyphasic sleep schedules (excluding nap or siesta schedules) on health, safety, and performance outcomes. Of 40,672 potentially relevant publications, with 2,023 selected for full-text review, 22 relevant papers were retained. We found no evidence supporting benefits from following polyphasic sleep schedules. Based on the current evidence, the consensus opinion is that polyphasic sleep schedules, and the sleep deficiency inherent in those schedules, are associated with a variety of adverse physical health, mental health, and performance outcomes. Striving to adopt a schedule that significantly reduces the amount of sleep per 24 hours and/or fragments sleep into multiple episodes throughout the 24-hour day is not recommended. (c) 2021 The Authors. Published by Elsevier Inc. on behalf of National Sleep Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell size homeostasis.