Reduced Number of Pediatric Orthopedic Trauma Requiring Operative Treatment during COVID-19 Restrictions: A Nationwide Cohort Study

Background and Aims:The coronavirus outbreak significantly changed the need of healthcare services. We hypothesized that the COVID-19 pandemic decreased the frequency of pediatric fracture operations. We also hypothesized that the frequency of emergency pediatric surgical operations decreased as well, as a result of patient-related reasons, such as neglecting or underestimating the symptoms, to avoid hospital admission.Materials and Methods:Nationwide data were individually collected and analyzed in all five tertiary pediatric surgical/trauma centers in Finland. Operations related to fractures, appendicitis, and acute scrotum in children aged above 16 years between March 1 and May 31 from 2017 to 2020 were identified. The monthly frequencies of operations and type of traumas were compared between prepandemic 3 years and 2020.Results:Altogether, 1755 patients were identified in five tertiary hospitals who had an emergency operation during the investigation period. There was a significant decrease (31%, p = 0.03) in trauma operations. It was mostly due to reduction in lower limb trauma operations (32%, p = 0.006). Daycare, school, and organized sports-related injuries decreased significantly during the pandemic. These reductions were observed in March and in April. The frequencies of appendectomies and scrotal explorations remained constant.Conclusion:According to the postulation, a great decrease in the need of trauma operations was observed during the peak of COVID-19 pandemic. In the future, in case similar public restrictions are ordered, the spared resources could be deployed to other clinical areas. However, the need of pediatric surgical emergencies held stable during the COVID-19 restrictions

Breaking the superfluid speed limit in a fermionic condensate

Coherent condensates appear as emergent phenomena in many systems. They share the characteristic feature of an energy gap separating the lowest excitations from the condensate ground state. This implies that a scattering object, moving through the system with high enough velocity for the excitation spectrum in the scatterer frame to become gapless, can create excitations at no energy cost, initiating the breakdown of the condensate—the well-known Landau velocity. Whereas, for the neutral fermionic superfluid 3He-B in the T = 0 limit, flow around an oscillating body displays a very clear critical velocity for the onset of dissipation, here we show that for uniform linear motion there is no discontinuity whatsoever in the dissipation as the Landau critical velocity is passed and exceeded. Given the importance of the Landau velocity for our understanding of superfluidity, this result is unexpected, with implications for dissipative effects of moving objects in all coherent condensate systems

Expression and Function of Androgen Receptor Coactivator p44/Mep50/WDR77 in Ovarian Cancer

Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis

Matrix metalloproteinases in human melanoma cell lines and xenografts: increased expression of activated matrix metalloproteinase-2 (MMP-2) correlates with melanoma progression

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumour progression and metastasis. In this study, we investigated the in vitro and in vivo expression patterns of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 mRNA and protein in a previously described human melanoma xenograft model. This model consists of eight human melanoma cell lines with different metastatic behaviour after subcutaneous (s.c.) injection into nude mice. MMP-1 mRNA was detectable in all cell lines by reverse transcription polymerase chain reaction (RT-PCR), but the expression was too low to be detected by Northern blot analysis. No MMP-1 protein could be found using Western blotting. MMP-2 mRNA and protein were present in all cell lines, with the highest expression of both latent and active MMP-2 in the highest metastatic cell lines MV3 and BLM. MMP-3 mRNA was expressed in MV3 and BLM, and in the non-metastatic cell line 530, whereas MMP-3 protein was detectable only in MV3 and BLM. None of the melanoma cell lines expressed MMP-9. TIMP-1 and TIMP-2 mRNA and protein, finally, were present in all cell lines. A correlation between TIMP expression level and metastatic capacity of cell lines, however, was lacking. MMP and TIMP mRNA and protein expression levels were also studied in s.c. xenograft lesions derived from a selection of these cell lines. RT-PCR analysis revealed that MMP-1 mRNA was present in MV3 and BLM xenografts, and to a lesser extent in 530. Positive staining for MMP-1 protein was found in xenograft lesions derived from both low and high metastatic cell lines, indicating an in vivo up-regulation of MMP-1. MMP-2 mRNA was detectable only in xenografts derived from the highly metastatic cell lines 1F6m, MV3 and BLM. In agreement with the in vitro results, the highest levels of both latent and activated MMP-2 protein were observed in MV3 and BLM xenografts. With the exception of MMP-9 mRNA expression in 530 xenografts, MMP-3, MMP-9, and TIMP-1 mRNA and protein were not detectable in any xenograft, indicating a down-regulated expression of MMP-3 and TIMP-1 in vivo. TIMP-2 mRNA and protein were present in all xenografts; interestingly, the strongest immunoreactivity of tumour cells was found at the border of necrotic areas. Our study demonstrates that of all tested components of the matrix metalloproteinase system, only expression of activated MMP-2 correlates with increased malignancy in our melanoma xenograft model, corroborating an important role of MMP-2 in human melanoma invasion and metastasis. © 1999 Cancer Research Campaig

Biosignals reflect pair-dynamics in collaborative work : EDA and ECG study of pair-programming in a classroom environment

Collaboration is a complex phenomenon, where intersubjective dynamics can greatly affect the productive outcome. Evaluation of collaboration is thus of great interest, and can potentially help achieve better outcomes and performance. However, quantitative measurement of collaboration is difficult, because much of the interaction occurs in the intersubjective space between collaborators. Manual observation and/or self-reports are subjective, laborious, and have a poor temporal resolution. The problem is compounded in natural settings where task-activity and response-compliance cannot be controlled. Physiological signals provide an objective mean to quantify intersubjective rapport (as synchrony), but require novel methods to support broad deployment outside the lab. We studied 28 student dyads during a self-directed classroom pair-programming exercise. Sympathetic and parasympathetic nervous system activation was measured during task performance using electrodermal activity and electrocardiography. Results suggest that (a) we can isolate cognitive processes (mental workload) from confounding environmental effects, and (b) electrodermal signals show role-specific but correlated affective response profiles. We demonstrate the potential for social physiological compliance to quantify pair-work in natural settings, with no experimental manipulation of participants required. Our objective approach has a high temporal resolution, is scalable, non-intrusive, and robust.Peer reviewe

A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis

All relevant data are within the paper and its Supporting Information files except for the primary TCR sequences. The data files for the primary TCR sequences are publicly deposited in the University of Massachusetts Medical School’s institutional repository, eScholarship@UMMS. The permanent link to the data is http://dx.doi.org/10.13028/M2CC70T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection.This work was supported by NIH R01 AI106725 as well as fellowship funding to SC from NIH AI T32 007061 and the UMass GSBS Millennium Program. The Small Animal Biocontainment Suite was supported in part by Center for AIDS Research Grant P30 AI 060354. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

IL-2 Mediates CD4+ T Cell Help in the Breakdown of Memory-Like CD8+ T Cell Tolerance under Lymphopenic Conditions

Background: Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8 + T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4 + T helper cells. Methodology/Principal Findings: Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8 + and CD4 + T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8 + T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8 + T cell self-reactivity. Conclusions/Significance: IL-2 mediates the cooperation of memory-like CD4 + and CD8 + T cells in the breakdown of crosstolerance, resulting in effector cytotoxic T lymphocyte differentiation and the induction of autoimmune disease

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c.) with keyhole limpet hemocyanin (KLH) or human papillomavirus (HPV)16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002) or 6 mg/animal poly I:C12U (p = 0.001) when compared with immunization with KLH alone. Notably, poly ICLC—but not CpG-C given at the same dose—also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell–activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01). This was paralleled by the reduced production of the homeostatic T cell–attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants for virus-specific Th1 and humoral immune responses in nonhuman primates

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions