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Serosurveys for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Greater Mekong Subregion (GMS) of Cambodia have been limited to those screening healthcare workers in 2 urban hospital-based settings [...]

Bioengineering and drug delivery technologies play an important role in bridging the gap between basic scientific discovery and clinical application of therapeutics. To identify the optimal treatment, the most critical stage is to diagnose the problem. Often these two may occur simultaneously or in parallel, but in this review, we focus on bottom‐up approaches in understanding basic immunologic phenomena to develop targeted therapeutics. This can be observed in several fields; here, we will focus on one of the original immunotherapy targets—cancer—and one of the more recent targets—regenerative medicine. By understanding how our immune system responds in processes such as malignancies, wound healing, and medical device implantation, we can isolate therapeutic targets for pharmacologic and bioengineered interventions. [ABSTRACT FROM AUTHOR]

Senescent cells (SnCs) are implicated in the pathogenesis of age-related diseases including osteoarthritis (OA), in part via expression of a senescence-associated secretory phenotype (SASP) that includes immunologically relevant factors and cytokines. In a model of posttraumatic OA (PTOA), anterior cruciate ligament transection (ACLT) induced a type 17 immune response in the articular compartment and draining inguinal lymph nodes (LNs) that paralleled expression of the senescence marker [p16.sup.INK4a] (Cdkn2a) and p21 (Cdkn1a). Innate lymphoid cells, [gamma][delta].sup.+] T cells, and [CD4.sup.+] T ells contributed to IL-17 expression. Intra-articular injection of IL-17-neutralizing antibody reduced joint degeneration and decreased expression of the senescence marker Cdkn1a. Local and systemic senolysis was required to attenuate tissue damage in aged animals and was associated with decreased IL-17 and increased IL-4 expression in the articular joint and draining LNs. In vitro, we found that Th17 cells induced senescence in fibroblasts and that SnCs skewed naive T cells toward Th17 or Th1, depending on the presence of TGF-[beta]. The SASP profile of the inflammation-induced SnCs included altered Wnt signaling, tissue remodeling, and cell-cycle pathways not previously implicated in senescence. These findings provide molecular targets and mechanisms for senescence induction and therapeutic strategies to support tissue healing in an aged environment., Introduction Regenerative medicine strategies aim to promote new tissue development but are often limited by systemic and environmental inhibitory factors such as aging or infection. Cellular senescence is associated with [...]

Objective: To determine the prevalence of COVID‐19 in a cohort of children undergoing tonsillectomy through assessment of B cell immune responses to SARS‐CoV‐2 in both peripheral blood and tonsil tissue. Methods: In this cohort study at a tertiary pediatric hospital (Children's National Hospital) in Washington, DC, we recruited 100 children undergoing tonsillectomy from late September 2020 to January 2021. Serum, peripheral blood cells, and tonsil tissue were collected and examined for immune reactivity to SARS‐CoV‐2. Parent‐reported clinical histories were compared to antibody and B‐cell responses. Results: Among 100 children undergoing tonsillectomy, 19% had evidence of immune responses to SARS‐CoV‐2 (CoV2+), indicating prior COVID‐19. In all seropositive participants, we detected SARS‐CoV‐2 specific B cells in both peripheral blood mononuclear cells and tonsils, providing evidence for tissue‐specific immunity in these children. Of the 19, 63% reported no known history of COVID‐19, and an additional 3 were asymptomatic or unaware of an acute infection when detected on pre‐surgery screen. Hispanic children represented 74% of CoV2+ subjects compared to 37% of the full cohort. 100% of CoV2+ children lived in a zip code with poverty level >10%. Conclusions: Nearly one‐fifth of children undergoing tonsillectomy at an urban U.S. hospital had evidence of prior COVID‐19 during the early pandemic, with the majority unaware of prior infection. Our results underscore the ethnic and socio‐economic disparities of COVID‐19. We found concordant evidence of humoral immune responses in children in both blood and tonsil tissue, providing evidence of local immune responses in the upper respiratory tract. Level of Evidence: 3 Laryngoscope, 133:1993–1999, 2023 [ABSTRACT FROM AUTHOR]

The rat model is an important resource in biomedical research due to its similarities to the human immune system and its use for functional studies. However, because of the preponderance of mouse models in foundational and mechanistic immunological studies, there is a relative lack of diverse, commercially available flow cytometry antibodies for immunological profiling in the rat model. Available antibodies are often conjugated to common fluorophores with similar peak emission wavelengths, making them hard to distinguish on conventional flow cytometers and restricting more comprehensive immune analysis. This can become a limitation when designing immunological studies in rat injury models to investigate the immune response to tissue injury. In addition, this lack of available antibodies limits the number of studies that can be done on the immune populations in lymphoid organs in other research areas. To address this critical unmet need, we designed a spectral flow cytometry panel for rat models. Spectral cytometry distinguishes between different fluorophores by capturing their full emission spectra instead of their peak emission wavelengths. This flow cytometry panel includes 24 distinct immune cell markers to analyze the innate and adaptive immune response. Importantly, this panel identifies different immune phenotypes, including tolerogenic, Type 1, and Type 2 immune responses. We show that this panel can identify unique immune populations and phenotypes in a rat muscle trauma model. We further validated that the panel can identify distinct adaptive and innate immune populations and their unique phenotypes in lymphoid organs. This panel expands the scope of previous rat panels providing a tool for scientists to examine the immune system in homeostasis and injury while pairing mechanistic immunological studies with functional studies. [ABSTRACT FROM AUTHOR]

As the COVID-19 pandemic took hold in the USA in early 2020, it became clear that knowledge of the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic individuals could inform public health policy decisions and provide insight into the impact of the infection on vulnerable populations. Two Clinical and Translational Science Award (CTSA) Hubs and the National Institutes of Health (NIH) set forth to conduct a national seroprevalence survey to assess the infection's rate of spread. This partnership was able to quickly design and launch the project by leveraging established research capacities, prior experiences in large-scale, multisite studies and a highly skilled workforce of CTSA hubs and unique experimental capabilities at the NIH to conduct a diverse prospective, longitudinal observational cohort of 11,382 participants who provided biospecimens and participant-reported health and behavior data. The study was completed in 16 months and benefitted from transdisciplinary teamwork, information technology innovations, multimodal communication strategies, and scientific partnership for rigor in design and analytic methods. The lessons learned by the rapid implementation and dissemination of this national study is valuable in guiding future multisite projects as well as preparation for other public health emergencies and pandemics. [ABSTRACT FROM AUTHOR]