Stroudskov4059

Background aims Natural killer (NK) cells are promising cells for immunotherapy of cancer, and there are ongoing efforts to improve their ex vivo expansion to clinically relevant numbers. This study focused on the development of a C1-, C2-, Bw4 killer cell immunoglobulin-like receptor (KIR) ligand and NKG2A ligand-containing feeder cell line for autonomous expansion of functional NK cells. Methods PC3PSCA-derived feeder cells expressing IL-2, 4-1BBL and membrane-bound IL-15-mutDAP12 (mIL-15d) fusion protein in combinations or alone were generated and used for expansion. Expanded NK cells were analyzed with respect to subpopulations, expression of NK cell receptors and immune checkpoint molecules as well as their cytotoxicity against K562 cells, cetuximab-marked tumor cells and autologous B cells. Results Only combinatorial expression of IL-2 plus 4-1BBL or IL-2, 4-1BBL plus mIL-15d in feeder cells efficiently expanded NK cells and supported selective outgrowth of NK cells from peripheral blood mononuclear cell samples. Best expansion of NK cells was achieved using PC3PSCA-IL-2-4-1BBL-mIL-15d feeder cells. Such expanded NK cells exhibited upregulation of natural cytotoxicity receptors, DNAM-1 and NKG2C and induced expression of high affinity IL-2 receptor, which were paralleled by attenuated KIR and increased expression of NKG2A and ILT2. In addition, elevated TIM-3 levels were noted and PD-1 and T cell immunoreceptor with Ig and ITIM domain (TIGIT) levels remained low. Expanded NK cells were highly cytolytic when encountering K562 cells and cetuximab-marked target cells but remained unresponsive to autologous B cells and target cells with protective levels of human leukocyte antigen. Conclusions Collectively, the results demonstrate the feasibility of PC3PSCA-IL-2-4-1BBL-mIL-15d feeder cells for robust expansion of NK cells, which remain tolerant to self and could be used in the future for adoptive cell therapy of cancer.Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.Background Since the onset of the new coronavirus pandemic, the world is facing a public health emergency. Repositioning hydroxychloroquine (HQ) seems to be a promising option. NSC 123127 Many emerging evidences have converged on the effectiveness of HQ in the treatment of Covid-19 infection. In a recent paper, Gautret et al. suggested that further works are needed to determine if HQ antiviral prophylaxis is useful, especially for healthcare workers. Methods The purpose of this paper is to assess the Covid-19 exposure and risks level among caregivers. For this, we performed research on internet and PubMed by crossing the following keywords healthcare givers, healthcare workers, doctors, nurses, coronavirus, Covid-19, mortality, infection rate, chloroquine, hydroxychloroquine. Results Data on healthcare worker's infection and mortality by Covid-19 are partial and are not systematically published. However, it seems that the infection rate varies between 3.8% and 9% depending on the country. Moreover, the mean age of this population is relatively old, especially in the OECD area. Conclusions Anti-Covid-19 HQ prophylaxis should be urgently accessed, especially for healthcare workers. It is to be hoped that HQ prophylaxis reduces the morbidity and mortality from Covid-19 infection among this population which is particularly exposed and relatively old.The outbreak of coronavirus disease 2019 (COVID-19) characterized with pneumonia, firstly occurred in Wuhan city, China, in December 2019 has so far spread in over 200 countries and territories in the world. One of the important goals in facing outbreaks of COVID-19 is to reduce the case fatality rate. We reported here that the fatality rate of COVID-19 in other provinces of mainland China was 0.82% (121/14,708), significantly lower than 6.62% (4512/68,128) in Hubei province (p less then 0.0001). The main reason for the lower fatality rate was likely due to the timely management of the patients in other provinces, highlighting the importance of timely management of patients in reducing the fatality rate of COVID-19.Objectives Common symptoms after thyroidectomy include voice change and throat and neck discomfort. But no common questionnaire has been developed. This study was performed to evaluate the reliability and validity of the Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ). Methods Fourty items of the TVSQ were divided into 20 items related to the "voice change" and "throat and neck discomfort" subcategories, using item generation. Through a reduction process, 20 items were removed and 20 items were used. For the patients after thyroidectomy, we evaluated the reliability and validity of each of the 20 items through item discrimination, test-retest reliability, concurrent validity, and external validity by comparing normal group and laryngeal disease patients. Also, the patients were compared before as well as 2 and 4 weeks after thyroidectomy. Results Item discrimination assessment showed a significant correlation between TVSQ total score and both the TVSQ "voice change" score (r = 0.908**) and TVSQ "throat and neck discomfort" score (r = 0.862**). Test-retest reliability assessment showed a significant correlation between TVSQ total scores at 2 and 4 weeks postoperatively (r = 0.764**). Concurrent validity assessment revealed that the TVSQ showed high correlations with other voice questionnaires (Voice Handicap Index, Reflux Finding Index, and Vocal Track Discomfort Scale; r = 0.538**-0.830**). External validity assessment revealed that the TVSQ was suitable for patients after thyroidectomy (P less then 0.000**). Conclusions Validity and reliability tests revealed that the TVSQ was suitable for assessment of the subjective feelings of patients with voice change and throat and neck discomfort after thyroidectomy.