Icahn School of Medicine at Mount Sinai

About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.

Induction of ICOS+CXCR3+CXCR5+ TH Cells Correlates with Antibody Responses to Influenza Vaccination

Abstract: Seasonal influenza vaccine protects 60 to 90% of healthy young adults from influenza infection. The immunological events that lead to the induction of protective antibody responses remain poorly understood in humans. We identified the type of CD4+ T cells associated with protective antibody responses after seasonal influenza vaccinations. The administration of trivalent split-virus influenza vaccines induced a temporary increase of CD4+ T cells expressing ICOS, which peaked at day 7, as did plasmablasts. The induction of ICOS was largely restricted to CD4+ T cells coexpressing the chemokine receptors CXCR3 and CXCR5, a subpopulation of circulating memory T follicular helper cells. Up to 60% of these ICOS+CXCR3+CXCR5+CD4+ T cells were specific for influenza antigens and expressed interleukin-2 (IL-2), IL-10, IL-21, and interferon-γ upon antigen stimulation. The increase of ICOS+CXCR3+CXCR5+CD4+ T cells in blood correlated with the increase of preexisting antibody titers, but not with the induction of primary antibody responses. Consistently, purified ICOS+CXCR3+CXCR5+CD4+ T cells efficiently induced memory B cells, but not naive B cells, to differentiate into plasma cells that produce influenza-specific antibodies ex vivo. Thus, the emergence of blood ICOS+CXCR3+CXCR5+CD4+ T cells correlates with the development of protective antibody responses generated by memory B cells upon seasonal influenza vaccination.

Antidepressant actions of histone deacetylase inhibitors.

Abstract: Persistent symptoms of depression suggest the involvement of stable molecular adaptations in brain, which may be reflected at the level of chromatin remodeling. We find that chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens, an important limbic brain region. This persistent increase in H3 acetylation is associated with decreased levels of histone deacetylase 2 (HDAC2) in the nucleus accumbens. Similar effects were observed in the nucleus accumbens of depressed humans studied postmortem. These changes in H3 acetylation and HDAC2 expression mediate long-lasting positive neuronal adaptations, since infusion of HDAC inhibitors into the nucleus accumbens, which increases histone acetylation, exerts robust antidepressant-like effects in the social defeat paradigm and other behavioral assays. HDAC inhibitor [N-(2-aminophenyl)-4-[N-(pyridine-3-ylmethoxy-carbonyl)aminomethyl]benzamide (MS-275)] infusion also reverses the effects of chronic defeat stress on global patterns of gene expression in the nucleus accumbens, as determined by microarray analysis, with striking similarities to the effects of the standard antidepressant fluoxetine. Stress-regulated genes whose expression is normalized selectively by MS-275 may provide promising targets for the future development of novel antidepressant treatments. Together, these findings provide new insight into the underlying molecular mechanisms of depression and antidepressant action, and support the antidepressant potential of HDAC inhibitors and perhaps other agents that act at the level of chromatin structure.

Commensal–dendritic-cell interaction specifies a unique protective skin immune signature

Abstract: The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.

National Trends in Rotator Cuff Repair

Abstract: Considerable literature exists regarding the surgical management of rotator cuff tears. Arthroscopic and open rotator cuff repairs have had comparable clinical results in the literature, with distinct advantages and disadvantages to both procedures1,2. Arthroscopy allows for preservation of the deltoid muscle3, improved ability to treat intra-articular lesions3, improved ability to mobilize and release the rotator cuff3, and less immediate postoperative pain4. Open and mini-open repair techniques allow for easier transosseous fixation to better replicate the footprint of the supraspinatus tendon5 and theoretically may provide a better potential for healing5, although transosseous equivalent constructs with use of suture anchors have been described that also show improved pressurized contact area6,7. Open repair and mini-open repair also allow for the placement of a modified Mason-Allen stitch, which, in comparison with the simple stitch, is a stronger method to grasp the tendon8,9. Several studies have examined geographic variation in the number of rotator cuff surgical procedures performed as well as variations in what surgeons deemed to be indications for rotator cuff surgery. For example, Vitale et al. found a large geographic variation in the number of rotator cuff surgical procedures that were performed in Medicare beneficiaries in 199210. This variation may have reflected a lack of clear operative indications and/or an understanding of the risks and benefits of surgery at the time of the study. With respect to surgical indications, Green et al. reported that surgeon preference was the primary deciding factor for performing inpatient rotator cuff surgery11. Dunn et al. also found significant variation in indications for rotator cuff surgery in a survey of selected members of the American Academy of Orthopaedic Surgeons as of the year 200212. Surgeons who had a higher procedure volume favored rotator cuff surgery more than those who had a lower volume12. Mini-open repair was the most frequently used method of repair (46.2%) followed by open (36.6%) and arthroscopic (14.5%)12. Despite many publications addressing rotator cuff repair techniques, indications for rotator cuff surgery, and outcomes in selected groups of patients, little information has been reported recently on trends of use at the national level. The purpose of our study was multifold. First, we sought to determine current trends in resource utilization for rotator cuff repairs, including type and setting of surgical treatment as well as type of anesthesia. The impact of age and sex on resource utilization was also examined. Finally, we also studied other variables (e.g., procedure length) that contribute to health-care costs. The hypotheses of our study were that (1) surgeons are now performing more arthroscopic rotator cuff repairs, (2) more of these repairs are being performed in ambulatory surgery settings, (3) patients who undergo surgery in an inpatient setting are more likely to be older and have more comorbidities, (4) surgical time is longer for arthroscopic repairs, and (5) the use of interscalene block for anesthesia is increasing.