Citations

Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA) along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8+ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8+ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.

Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16INK4a promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span.

Significant functional impairment and psychological distress have been observed in adolescent patients with postural orthostatic tachycardia syndrome (POTS). Interdisciplinary rehabilitation programs have been shown to be beneficial in the treatment of chronic pain in adults and adolescents. Only preliminary data have examined interdisciplinary rehabilitation efforts in patients with POTS. This study evaluated the impact of an interdisciplinary rehabilitation program on the functional impairment and psychological distress in 33 adolescents diagnosed with POTS. Patients included in the study were adolescents ages 11 to 18 diagnosed with POTS. Measures completed at admission and discharge from the program included the Functional Disability Index, Center for Epidemiological Studies–Depression–Child scale, and the Pain Catastrophizing Scale for Children. After participation in the 3-week program, adolescents with POTS demonstrated a significant increase in overall functional ability and significant reductions in depression and catastrophizing.

Abstract Interest among the zebrafish community in education and science accessibility for all ages has increased. At the 8th Annual Zebrafish Disease Models Conference (ZDM8), a specifically designed session enabled professional scientists, educators, and students to have a venue to present their science, discuss ideas in education, and partner to navigate a scientific meeting as an educational experience. This meeting report describes the format of the Platform Session as well as challenges and future plans to leverage impact of conferences on the local communities.

Background: Quality measures are now commonplace and are increasingly tied to financial incentives. We reviewed the existing quality measures that address the upper limb and tested the null hypothesis that structure (capacity to deliver care), process (appropriate care), and outcome (the result of care) measures are equally represented. Methods: We systematically reviewed MEDLINE/PubMed, Embase, Google Scholar, the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines, the National Quality Forum, the Agency for Healthcare Research and Quality, and the Physician Quality Reporting System for quality measures addressing upper limb surgery. Measures were characterized as structure, process, or outcome measures and were categorized according to their developer and their National Strategy for Quality Improvement in Health Care (National Quality Strategy) priority as articulated by the U.S. Department of Health & Human Services. Results: We identified 134 quality measures addressing the upper limb: 131 (98%) process and three (2%) outcome measures. The majority of the process measures address the National Quality Strategy priority of effective clinical care (90%), with the remainder addressing communication and care coordination (5%), person and caregiver-centered experience and outcomes (4%), and community/population health (1%). Conclusions: Our review identified opportunities to develop more measures in the structure and outcome domains as well as measures addressing patient and family engagement, public health, safety, care coordination, and efficient use of resources. The most common existing measures—process measures addressing care—might not be the best measures of upper limb surgery quality given the relative lack of evidence for their use in care improvement.