Abstract. Myeloid-derived suppressor cells (MDSCs) have been identified in the majority of patients and experimental mice with tumors by their suppression of T cell activation. MDSCs have also been reported to be associated with chronic inflammation. In advanced cancer, the T helper (Th) cell balance tends to shift from Th1 to Th2 predominance, and immune function, including cell-mediated immunity, is impaired by cytokines produced by Th2 cells. The present study examined the correlations between MDSC levels and inflammation, immune suppression, malnutrition, and poor prognosis in 155 patients with breast cancer. The levels of MDSCs in preoperative patients and in patients with recurrent breast cancer were significantly higher compared with postoperative patients, patients with recurrent breast cancer who received chemotherapy and healthy volunteers. The MDSC levels of preoperative patients were significantly positively correlated with interleukin (IL)-6 production by peripheral blood mononuclear cells (PBMCs), the neutrophil/lymphocyte ratio and C-reactive protein, and were negatively correlated with the production of interferon-γ and IL-12, serum concentration of rapid turnover protein, and the stimulation index. These patients were divided into two groups based on the levels of MDSCs. In preoperative patients with MDSC levels >1.0% of total PBMCs, the overall survival of patients with stage IV disease was significantly shorter compared with other disease stages, and was also significantly shorter compared with patients with MDSC levels <1.0% of total PBMCs. Thus, the MDSC levels of preoperative patients may function as a good prognostic indicator, particularly in patients with advanced breast cancer.

Abstract. Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. While many studies have investigated the ANXA1 expression in various tumor types, the role of ANXA1 is not fully understood. Therefore, in the present study, we evaluated the ANXA1 expression in 211 breast cancer patients and compared the levels with clinicopathological factors. ANXA1 was positively expressed in 31 (14.7%) of the 211 cases in our cohort, and these positive cases were associated with triple-negative breast cancer (TNBC) (P=0.007) and venous invasion (P=0.028). The in vitro cell experiment found that the MDA-MB-231 cell line, which is a TNBC cell line, highly expressed ANXA1. Using this cell line, the functional role of ANXA1 in breast cancer was revealed and the knockdown of ANXA1 by specific siRNA demonstrated a significant reduction in cellular invasion. Further experiments indicated that ANXA1 was induced by hypoxia with hypoxia-inducible factor-1α induction. These results suggested that ANXA1, which enhanced breast cancer invasion and metastasis under hypoxia, were significantly associated with the worst patient outcome. This is particularly noted in TNBC, the group of breast cancer with the worst outcome for which new therapeutic implications are required. IntroductionBreast cancer is a leading cause of cancer related mortality among females worldwide and its incidence and mortality rate have been increasing throughout the recent years (1). The treatment of breast cancer has progressed over the past three decades with the development of the combination of chemotherapy, endocrine therapies and human epidermal growth factor receptor 2 (HER2)-targeted therapies (2-5). However, triple-negative breast cancer (TNBC), which is defined by the lack of the estrogen receptor (ER), the progesterone receptor (PgR) and HER2 expression, has not fully benefited from such advances in treatment. Therefore, patients with TNBCs are currently categorized as a sub group with the worst possible outcome. Although recent progress in gene sequencing technology has revealed the genetic profile of breast cancer including that of TNBC, the effort to understand breast cancer based on the diverse view from a more inclusive perspective is still needed (6-8).Annexin A1 (ANXA1) is a 37-kDa calcium-dependent phospholipid-linked protein belonging to the annexin superfamily and it is related to anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis (9-11). However, through those functions, ANXA1 is involved in tumorigenesis and the pivotal role of ANXA1 is not clearly understood. One of the main reasons for this is due to the fact that the functional role of ANXA1 in malignant tumors is quite different depending on the cancer type, such as head-and-neck, esophageal, gastric, colorectal, pancreatic, hepatic and prostate cancer (12-19). While ANXA1 is highly expressed in malignant tumors (20,21), some stu...

PURPOSEWe developed linkages using interoperable standardized nursing terminologies, NANDA International (NANDA‐I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC), to present initial guidance for the development of care plans focused on COVID‐19 for nurses practicing in community or public health roles.METHODSSeven nurse experts identified the linkages of NANDA‐I, NOC and NIC for our work related to the COVID‐19 pandemic. A model was developed to guide the project. The first step in creating linkages focused on the identification of nursing diagnoses. Then, for each nursing diagnosis, outcomes aligned with all components of the diagnosis were categorized and a list of nursing interventions was selected. The experts used their clinical judgment to make final decisions on the linkages selected in this study.FINDINGSTwo community level nursing diagnoses were identified as key problems appropriate for a pandemic related to COVID‐19: Deficient Community Health and Ineffective Community Coping. For the nursing diagnosis Deficient Community Health, eight nursing outcomes and 12 nursing interventions were selected. In comparison for the nursing diagnosis, Ineffective Community Coping, nine nursing outcomes and 18 nursing interventions were identified. A total of40 concepts were identified for future development across the three classifications.CONCLUSIONSThe nursing diagnoses, outcomes and interventions selected during this linkage process provide knowledge to support the community challenged with responding to the COVID‐19 pandemic, provide the opportunity to quantify the impact of nursing care, and enhance nursing practice by promoting the use of three standardized terminologies.IMPLICATIONS FOR NURSING PRACTICENANDA‐I, NOC and NIC linkages identified in this manuscript provide resources to support clinical decisions and care plan development for nurses practicing in the community.

PurposeTo provide guidance to nurses caring for individuals with COVID‐19, we developed linkages using interoperable standardized nursing terminologies: NANDA International (NANDA‐I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). We also identified potential new NANDA‐I nursing diagnoses, NOC outcomes, and NIC interventions for future development related to nurses’ role during a pandemic.MethodsUsing a consensus process, seven nurse experts created the linkages for individuals during the COVID 19 pandemic using the following steps: (a) creating an initial list of potential nursing diagnoses, (b) selecting and categorizing outcomes that aligned with all components of each nursing diagnosis selected, and (c) identifying relevant nursing interventions.FindingsA total of 16 NANDA‐I nursing diagnoses were identified as the foundation for the linkage work, organized in two dimensions, physiological and psychosocial. A total of 171 different NOC outcomes were identified to guide care based on the nursing diagnoses and 96 NIC interventions were identified as suggested interventions. A total of 13 proposed concepts were identified for potential future development across the three classifications.ConclusionsThe linkages of nursing diagnoses, outcomes, and interventions developed in this article provide a guide to enhance nursing practice and determine the effectiveness of nurses’ contribution to patient outcomes for individuals at risk for or infected by COVID‐19.Implications for nursing practiceNANDA‐I, NOC, and NIC linkages identified in this paper are an important example of the value of using standardized nursing terminologies to guide and document nursing care. When included in electronic health record databases and used widely, the data generated from the care plans can be used to create new knowledge about how to better improve outcomes for patients with COVID‐19.

Escherichia coli delta prc mutants lacking periplasmic protease Prc, which was originally found involved in the C-terminal processing of penicillin-binding protein (PBP) 3, show thermosensitive growth at low osmolarity. We isolated thermoresistant revertants containing extragenic suppressor (spr) mutations. In the prc+ background the mutations also caused thermosensitivity at low osmolarity. They were all mapped at about 48 min on the chromosome and most probably allelic to one another. From this chromosomal region we cloned a gene that could correct the thermosensitive defect of an spr mutant, which turned out to be a multicopy suppressor of spr. Analysis of the nucleotide sequence predicted that the gene would code for a low-molecular-weight PBP, and penicillin-binding experiments revealed the product to be PBP 7. Disruption of the gene on the chromosome caused no apparent growth defect. PBP 7 seemed to be degraded by protease Prc. Overproduction of mutant PBP 7 that had the active site serine residue replaced with alanine did not correct the spr thermosensitivity, suggesting importance of the DD-endopeptidase activity in the multicopy suppression.