Comparison of assays measuring extracellular vesicle-tissue factor in plasma samples: Communication from the ISTH SSC Subcommittee on Vascular Biology.

BACKGROUND: Scientific and clinical interest in extracellular vesicles (EVs) is growing. EVs that expose tissue factor (TF) bind factor VII/VIIa and can trigger coagulation. Highly procoagulant TF-exposing EVs are detectable in the circulation in various diseases, such as sepsis, COVID-19 or cancer. Many in-house and commercially available assays have been developed to measure EV-TF activity and antigen but only a few studies have compared some of these assays. The ISTH SSC Subcommittee on Vascular Biology initiated a multicenter study to compare the sensitivity, specificity and reproducibility of these assays. MATERIALS AND METHODS: Platelet-depleted plasma samples were prepared from blood of healthy donors. The plasma samples were spiked either with EVs from human milk, or EVs from TF-positive and TF-negative cell lines. Plasma was also prepared from whole human blood with or without LPS stimulation. Twenty-one laboratories measured EV-TF activity and antigen in the prepared samples using their own assays representing 18 functional and 9 antigenic assays. RESULTS: There was a large variability in the absolute values for the different EV-TF activity and antigen assays. Activity assays had higher specificity and sensitivity compared to antigen assays. In addition, there was a large intra-assay and inter-assay variability. Functional assays that used a blocking anti-TF antibody or immunocapture were the most specific and sensitive. Activity assays that used immunocapture had a lower coefficient of variation compared to assays that isolated EVs by high-speed centrifugation. CONCLUSION: Based on this multicenter study, we recommend measuring EV-TF using a functional assay in the presence of an anti-TF antibody.

Caring for people with intellectual disabilities: Insights from a cross-sectional study among nursing students.

BACKGROUND: Caring for people with intellectual disabilities poses substantial challenges. Nursing students' emotions, thoughts, and behaviors during their education in the context of people with intellectual disabilities, remain relatively unexplored. OBJECTIVES: To examine nursing students' emotions, thoughts, competence, and expected professional behaviors in care provision for people with intellectual disabilities, as well as to identify factors associated with their expected professional behaviors with this population. DESIGN: A cross-sectional study using a closed self-report questionnaire and one open-ended question. SETTING: The largest academic nursing department in Israel. PARTICIPANTS: Of 245 sophomore nursing students, 177 agreed to participate (71.4 % response rate). METHODS: The study measured feelings, thoughts, competence, and expected professional behaviors in care provision for people with intellectual disabilities based on the Multidimensional Attitudes Scale. One open-ended question addressed how students believe their competence in caring for people with intellectual disabilities could be improved during their nursing studies. A hierarchical linear regression analysis was performed to investigate the contribution of emotions, thoughts, and competence to explaining expected behaviors in care provision. The significance of the model and the R2 were calculated. The open-ended question was analyzed by the constant comparative method. RESULTS: Negative emotions and thoughts (ß = -0.37, 95 % CI -0.47; -0.15 and ß = -0.33, 95 % CI -0.39; -0.13, respectively), along with positive emotions (ß = 0.25, 95 % CI 0.07;0.33), showed significant associations with expected professional behaviors. Qualitative analysis revealed three key themes: communication concern, knowledge gap, and curiosity. The findings of the open-ended question corroborate the quantitative findings. CONCLUSION: It is important to realize that in order to develop quality professional skills for caring for people with intellectual disability, nursing educators must adopt a deep discussion of negative emotions and thoughts with their students regarding people with intellectual disabilities. Ignoring these negative emotions and thoughts can exacerbate the neglect of people with intellectual disabilities' health needs.

Decision-making process regarding passive euthanasia: Theory of planned behavior framework.

BACKGROUND: Nurses have an essential role in caring for end-of-life patients. Nevertheless, the nurse's involvement in the passive euthanasia decision-making process is insufficient and lower than expected. OBJECTIVES: To explore factors associated with nurses' intention to be involved in non-treatment decisions (NTD) regarding passive euthanasia decision-making versus their involvement in the palliative care of patients requesting euthanasia, using the Theory of Planned Behavior (TPB) framework. DESIGN: A cross-sectional study utilizing a random sample. PARTICIPANTS AND RESEARCH CONTEXT: The study was conducted in one of the largest hospitals in Israel among 125 nurses employed in internal and surgical care wards. Data was collected through face-to-face interviews between March and April 2019. METHOD: A closed structured questionnaire was developed according to TPB instructions. A paired sample t test and two multiple hierarchical regressions were conducted. Variance explained (R2) and the significance of F change were calculated for each regression. The study used the STROBE statement guideline. ETHICAL CONSIDERATIONS: The study was approved by the hospital's Helsinki Committee (#20.11.2017). FINDINGS: A paired sample t test revealed that nurses' involvement in the palliative care of patients requesting passive euthanasia was significantly higher than in NTD regarding euthanasia. Regression analyses revealed that nurses' position and attitudes explain their intention to be involved in decision-making; attitudes and perceived behavioral control explain nurses' intention to be involved in the care of patients requesting euthanasia. CONCLUSIONS: According to the TPB, nurses' attitudes explained their intention to participate in decision-making regarding passive euthanasia. It is recommended to enhance open discussion of this complex issue to encourage nurses' willingness to participate in NTD decision-making regarding euthanasia.

Factors affecting intent to perpetrate violence against nurses: Theory of Planned Behavior approach.

BACKGROUND: The Theory of Planned Behavior (TPB) has been found to predict target behaviors. The literature examining this model lacks attention to violence toward nurses. PURPOSE: To explore the association between the public's exposure to violence and intention to employ violence toward nurses, under the TPB framework. METHODS: A cross-sectional study (705 participants) employed a self-report questionnaire. Path analysis assessed TPB variables' mediation between prior exposure to violence and violent intent toward nurses. DISCUSSION: The TPB variables, that is attitudes, subjective norms, and perceived control, mediated only the association between exposure to physical violence and intention to act violently. Subjective norms were the strongest mediator. The explained variance was 31%. CONCLUSION: When addressing violence against nurses, policymakers must consider attitudes, subjective norms, and perceived control among patients and their attendants. Violence directed at nurses and health care workers reflects societal violence and the "upstream approaches" needed to mitigate violence in health care settings.

Sophomore nursing students' perception of their Professional Behavior toward Rehabilitation patients: a cross-sectional study.

BACKGROUND: Rehabilitation is considered one of the elements of universal health coverage, emphasizing its importance for every person in need throughout the life course. Nurses play a pivotal role in the rehabilitation team as they possess the competencies to help individuals manage health problems and maximize potential well-being. Yet, little is known regarding knowledge of this subject among nursing students, as well as regarding their attitudes, thoughts, and professional behavior. This study aimed to explore: (a) Sophomore students' attitudes, feelings, thoughts, and professional behavior toward rehabilitation patients; and (b) Differences in the research variables as affected by students' previous exposure to rehabilitation patients. METHODS: A cross-sectional survey design among sophomore nursing students. A questionnaire was distributed through a commercial internet survey provider (Qualtrics.com) before the beginning of a mandatory course on "nursing rehabilitation", introduced for the first time in 2022 in all Israeli universities. Students were divided into three groups according to their previous exposure to rehabilitation patients: no professional or personal previous exposure to rehabilitation patients; previous professional or personal exposure to rehabilitation patients; and previous exposure to rehabilitation patients both in one's professional and personal life. The study adhered to the STROBE guidelines. RESULTS: The sample consisted of 122 participants. Significant differences were found between the groups by their previous exposure to rehabilitation patients. Participants with no previous exposure to rehabilitation patients were found to have lower self-perceived capability to care for rehabilitation patients and more negative professional behavior toward rehabilitation patients and their families compared to the other two groups (H = 22.06, p = 0.006, H = 23.86, p = 0.03, respectively). No other statistical differences were observed between the groups. CONCLUSIONS: The findings emphasize the importance of exposing students to the field of nursing rehabilitation and to the care of rehabilitation patients. Exposure to nursing rehabilitation specifically during one's studies, through theoretical learning and clinical experience, can promote positive attitudes, professional values, and positive professional behavior toward these patients and their families.

Characterization of extracellular vesicles in COVID-19 infection during pregnancy.

Introduction: SARS-CoV-2 infection may cause a severe inflammatory response, inflicting severe morbidity and mortality. This risk is modestly increased in pregnant patients. Despite the hypercoagulability and immunosuppression associated with pregnancy, most pregnant women experience a mild COVID-19 infection. Maternal extracellular vesicles (EVs) may interact with endothelial and immune components to facilitate a favorable disease course. This pilot study aimed to explore the characteristics of EVs released during COVID-19 infection occurring during the third trimester of pregnancy. Methods: In this prospective study, blood samples were obtained from 16 healthy non-pregnant (NP), 18 healthy-pregnant (HP), and 22 COVID-19 positive pregnant subjects (CoV-P). Disease course and pregnancy outcomes were assessed and EVs were characterized. Of note, limited volumes of sample acquired from the subjects made it necessary to use smaller and different subsets of samples for each analysis. Results: The majority (91%) of the COVID-19-pregnant subjects (18 mild and 2 moderate disease) experienced good pregnancy-related outcomes. EV concentrations were higher in healthy-pregnant subjects compared to non-pregnant subjects (p = 0.0041) and lower in COVID-19-pregnant subjects compared to healthy-pregnant subjects (p = 0.0150). CD63 exosome marker expression was higher in EVs of healthy-pregnant subjects and COVID-19-pregnant subjects compared to EVs of non-pregnant subjects (p = 0.0149, p = 0.0028, respectively). Similar levels of SARS-CoV-2 entry proteins (ACE-2 and TMPRSS2) were found in all three groups. Cytokine content increased in healthy-pregnant subject-EVs compared to non-pregnant EVs, while IL-2 and IL-6 levels were decreased in COVID-19-pregnant subject-EVs compared to healthy-pregnant subject-EVs (p = 0.043, p = 0.0390, respectively). CD8+, cytotoxic T-cell marker, was lower in non-pregnant EVs compared to healthy-pregnant subject-EVs and to COVID-19-pregnant subjects (p = 0.0108, p < 0.0001, respectively). COVID-19- pregnant subject-EVs demonstrated higher levels of platelet activation marker (CD62P) than non-pregnant (p = 0.0327) and healthy-pregnant subjects (p = 0.0365). Endothelial marker EV-CD144+ was lower in healthy-pregnant subjects versus non-pregnant subjects (p = 0.0093), but similar in COVID-19-pregnant and non-pregnant subjects. Other EVs' coagulation markers/activity, D-Dimer and fibrinogen levels were similar in healthy-pregnant subjects and COVID-19 positive pregnant subjects. Conclusion: COVID-19 positive pregnant subjects' EVs demonstrated an attenuated inflammatory response, with no additional activation of the coagulation system.

The role of sense of coherence in workplace violence directed at nurses in the shadow of COVID-19: A cross-sectional study.

AIMS: To explore (a) the associations between sense of coherence (SOC), previous exposure to COVID-19, and the intention to act violently towards nurses, and (b) the role of SOC and sociodemographic variables as risk or protective factors involved in the intention to act violently. DESIGN: A cross-sectional study with a convenience sample. METHODS: A structured self-report questionnaire was distributed from February to March 2022. The questionnaire included socioeconomic variables, previous exposure to COVID-19, and a validated questionnaire on SOC. Three vignettes (online shaming, verbal and physical violence) describing nurse-patient communication conflicts were presented to participants. A multinomial logistic regression was conducted to explore the associations with acting violently by comparing three options of no/sometimes/high intention to act violently. The study adhered to STROBE guidelines. RESULTS: Questionnaires were completed by 808 adults. SOC and religiosity were revealed as protective factors in the three vignettes. Verbal violent behaviour was found to be a risk factor for online and physical violent behaviour intention. Previous exposure to COVID-19, non-academic education, and ethnicity were found to be risk factors for the intention to behave violently toward nurses. CONCLUSION: The findings suggest that training nurses in practical SOC dimensions (enhancing comprehensible, manageable and meaningful treatment processes) may reduce patients' lack of understanding and frustration and, in turn, reduce the tendency to behave violently. IMPACT: This study focused on SOC as a variable that may affect the intention to act violently towards nurses. The results reveal that SOC may be a protective factor, where people with higher SOC will have less intention to behave violently towards nurses. The results can provide an insight for nurses, nurse leaders and policymakers, towards supplying coherent and cultural competency treatment processes for patients and assisting nurses in dealing with stressful situations during normal routines and pandemics. PATIENT OR PUBLIC CONTRIBUTION: The questionnaire was distributed among the general public by master's degree nursing students. The students distributed the questionnaires among their friends and acquaintances using a snowball-sampling approach.

The Role of Extracellular Vesicles (EVs) in Chronic Graft vs. Host Disease, and the Potential Function of Placental Cell-Derived EVs as a Therapeutic Tool.

Chronic graft-versus-host disease (cGVHD) presents with dermal inflammation and fibrosis. We investigated the characteristics of extracellular vesicles (EVs) obtained from cGVHD patients, and their potential effects on human dermal fibroblast (NHDF) cells. The anti-inflammatory and anti-fibrotic effects of placental EVs were also explored given their known anti-inflammatory properties. Fourteen cGVHD patients' EVs contained higher levels of fibrosis-related proteins, TGFß and α-smooth muscle actin (αSMA), compared to EVs from thirteen healthy subjects. The exposure of NHDF cells to the patients' EVs increased the NHDF cells' TGFß and αSMA expressions. Placental EVs derived from placental-expanded cells (PLX) (Pluri Inc.) and human villous trophoblast (HVT) cells expressing the mesenchymal markers CD29, CD73, and CD105, penetrated into both the epidermal keratinocytes (HACATs) and NHDF cells. Stimulation of the HACAT cells with cytokine TNFα/INFγ (0.01-0.1 ng/µL) reduced cell proliferation, while the addition of placental EVs attenuated this effect, increasing and normalizing cell proliferation. The treatment of NHDF cells with a combination of TGFß and placental HVT EVs reduced the stimulatory effects of TGFß on αSMA production by over 40% (p = 0.0286). In summary, EVs from patients with cGVHD can serve as a biomarker for the cGVHD state. Placental EVs may be used to regulate dermal inflammation and fibrosis, warranting further investigation of their therapeutic potential.

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.

Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies. Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated. Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC. Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

Extracellular Vesicles of COVID-19 Patients Reflect Inflammation, Thrombogenicity, and Disease Severity.

Severe COVID-19 infections present with cytokine storms, hypercoagulation, and acute respiratory distress syndrome, with extracellular vesicles (EVs) being involved in coagulation and inflammation. This study aimed to determine whether coagulation profiles and EVs reflect COVID-19 disease severity. Thirty-six patients with symptomatic COVID-19 infection with mild/moderate/severe disease (12 in each group) were analyzed. Sixteen healthy individuals served as controls. Coagulation profiles and EV characteristics were tested by nanoparticle tracking analysis (NTA), flow cytometry, and Western blot. While coagulation factors VII, V, VIII, and vWF were comparable, significant differences were found in patients' D-Dimer/fibrinogen/free protein S levels compared to controls. Severe patients' EVs displayed higher percentages of small EVs (<150 nm) with increased expression of exosome marker CD63. Severe patients' EVs displayed high levels of platelet markers (CD41) and coagulation factors (tissue factor activity, endothelial protein C receptor). EVs of patients with moderate/severe disease expressed significantly higher levels of immune cell markers (CD4/CD8/CD14) and contained higher levels of IL-6. We demonstrated that EVs, but not the coagulation profile, may serve as biomarkers for COVID-19 severity. EVs demonstrated elevated levels of immune- and vascular-related markers in patients with moderate/severe disease, and may play a role in disease pathogenesis.

Perceptions of children with cancer and their parents regarding illness: A qualitative study.

PURPOSE: The current study aims to understand inter-generational differences and similarities in the perception of illness and the available resources employed by children with cancer and their parents. METHODS: A qualitative descriptive research design was utilized, including face-to-face interviews with 108 parent-child dyads where the children had been diagnosed with cancer, by means of a semi-structured questionnaire. The participants were recruited from two pediatric hematology-oncology wards in two different hospitals in Israel. The data were analyzed using conventional qualitative content analysis. Debriefing and inter-rater reliability methods were utilized. FINDINGS: Similarities were found between the coping of children and parents with the illness. Children with cancer and their parents can find bright sides and support for coping, such as different perspectives on life, faith, positive thoughts, and family assistance. Most of the differences between the perceptions of children and parents relate to the difficulties encountered. While parents are mainly concerned about the long-term impact, children contend with ordeals involving the here-and-now. CONCLUSIONS: Parents and children demonstrate a dual process in their challenging journey. Positive and facilitating factors are intertwined with the aggravating aspects, which exist side by side. PRACTICE IMPLICATIONS: Nursing staff should advise children and their parents to attain and use external and internal sources of support found in this study to help them deal with cancer.

Positive affect and fatigue as predictors of anti-inflammatory IL-10 concentrations among colorectal cancer patients during adjuvant chemotherapy.

OBJECTIVES: (1) To examine the relationships of positive and negative affect and symptoms of depression, anxiety, and fatigue at baseline with the anti-inflammatory cytokine IL-10 concentrations in serum at three points in colorectal cancer patients; and (2) to assess the relationship between these factors and disease recurrence or mortality after a median follow-up of 24 months. METHODS: In a prospective trial, 92 stage II or III colorectal cancer patients scheduled to receive standard chemotherapy were enrolled. Blood samples were collected prior to start of chemotherapy onset (T0), 3 months later (T1), and upon chemotherapy completion (T2). RESULTS: IL-10 concentrations were similar across the time points. Linear mixed-effects model analysis showed that controlling for confounders, higher positive affect and lower fatigue pretreatment (T0) predicted IL-10 concentrations across the time points (estimate = 0.18, SE = 0.08, 95% CI = 0.03, 0.34, p < .04 and estimate = -0.25, SE = 0.12, 95% CI = -0.50, 0.01, p < .04, respectively). Depression at T0 significantly predicted higher disease recurrence and mortality (estimate = 0.17, SE = 0.08, adjusted OR = 1.18, 95% CI = 1.02, 1.38, p = .03). CONCLUSIONS: We report on associations not previously assessed between positive affect and fatigue and the anti-inflammatory cytokine IL-10. Results add to previous findings suggesting that positive affect and fatigue could have a role in anti-inflammatory cytokine dysregulation.

Intervention training of urology healthcare staff to counsel acute care inpatients on smoking cessation: An evaluation study.

AIM: To evaluate the differences, following intervention training, in the knowledge, attitudes, role perception, self-capacity and intention of urology staff to counsel inpatients on smoking cessation. DESIGN: A descriptive evaluation study of intervention training in counselling on smoking cessation. The study was designed following guidance by the Medical Research Council. METHODS: The evaluation was based on a closed-end questionnaire with four time-point measurements from May 2018-December 2019 (N = 29 at each time-point). A repeated measure within-subjects ANOVA was conducted to explore the variance in participants' attitudes, role perception, self-capacity and intention to counsel patients regarding smoking cessation. Eta squared and Bonferroni post hoc tests were used to interpret the results. RESULTS: No change was observed in the research variables after theoretical science-based learning of the smoking hazards and the benefits of cessation. A statistically significant difference was found following procedural knowledge based on training, practical experience and skill development.

Social determinants and adherence to recommended COVID-19 vaccination among the Arab ethnic minority: A syndemics framework.

Background: Since the mass vaccination against SARS-CoV-2 was launched in Israel, the Arab ethnicity minority had lower vaccine uptake. The syndemics theory suggests a closely interrelated complex of health and social crises among vulnerable societies results in an increased disease burden or in more adverse health conditions. Syndemics may explain the health disparities between different people or communities. Likewise, acculturation was found to be associated with different health outcomes among minority populations. The purpose of the study is to explore the association between syndemic construct, acculturation style, and adherence to recommended COVID-19 vaccination among the Arab ethnicity in Israel. Methods: A cross-sectional study among 305 participants who completed a self-report questionnaire. Syndemic construct (syndemics score and syndemics severity) was calculated from the participants' health behavior index, self-rated health status, and adherence to flu vaccination. Four acculturation strategies were defined according to Barry's acculturation model: assimilation, integration, separation, and marginalization style. Linear regression (stepwise method) was conducted to determine the explanatory factors for COVID-19 vaccine adherence. Results: Assimilation and separation acculturation styles and syndemics severity were significantly associated with higher adherence to the recommended COVID-19 vaccination (B = 1.12, 95%CI = 0.34-1.98; B = 0.45, 95%CI = 0.10-0.80; B = 0.18, 95%CI = 0.09-0.28; respectively). The explained variance of the model (R 2) was 19.9%. Conclusion: Syndemics severity, assimilation and separation acculturation styles were associated with higher adherence to recommended COVID-19 vaccination in the Israeli Arab minority population. Syndemics score was not associated with recommended COVID-19 vaccination. To encourage COVID-19 vaccination among minority communities, campaigns should be tailored to the social determinants in a sensitive and individualized manner.

Reducing health disparities: Adherence to referrals for further diagnosis among asylum seeking children.

OBJECTIVE: Asylum-seeking children are most vulnerable to health problems and non-utilization of health amenities. The aim of the study was to compare adherence with referrals for further diagnostic tests among asylum-seeking children and native Israeli children. DESIGN: A retrospective cohort study. SAMPLE: The study was conducted among 3508 children born in 2016-2017, with two randomized sample groups: Israeli children (n = 243) and asylum-seeking children (n = 271). Data were retrieved from the children's medical files. MEASUREMENTS: Referrals for further diagnostic tests were defined as written referrals by a public health nurse or pediatrician. Data collected included the child's and mother's details, as well as data on referrals. A multiple logistic regression test was performed to detect risk variables for non-adherence to referrals. RESULTS: No differences were found between the groups regarding adherence to referrals for further diagnosis. Having medical insurance did not explain adherence to referrals. Asylum-seeking children have more need for further follow-up than do Israeli children. CONCLUSION: Asylum-seeking children and Israeli children respond similarly to the preventive health services offered with equal accessibility. Public health nurses have an essential role in encouraging adherence to screening tests and to referrals for further diagnostic tests and in mitigating health disparities among asylum-seeking children.

The Role of Science-Based Knowledge on the SARS-CoV-2 Virus in Reducing COVID-19-Induced Anxiety among Nurses.

The COVID-19 infection has generated not only a risk of morbidity and mortality but also resulted in an enormous psychological impact on healthcare providers and the general public. This study aimed to evaluate the prevalence of anxiety and identify the role of protective factors. A two-part cross-sectional study was conducted, by means of an online questionnaire. Part 1 investigated 562 registered nurses, nursing students, and the general public. Participants were assessed for anxiety symptoms with the State-Trait-Anxiety Inventory. A one-way ANCOVA analysis revealed that nurses had the highest level of anxiety compared to the general public and students, with 26% of them reporting severe anxiety. To identify how anxiety can be mitigated, the Part 2 study was focused on registered nurses from Part 1. Multiple regression revealed that a higher level of science-based knowledge of COVID-19 and professional experience were associated with a lower level of anxiety among nurses. The findings suggest that nurses are a vulnerable population prone to anxiety symptoms resulting from the COVID-19 pandemic. Having a deeper science-based understanding of COVID-19 may protect nurses from anxiety. This study underlines the importance of deep evidence-based knowledge for health providers, which may be generalized to a possible future emergency disaster.

Parents' Adherence to Childhood Screening Tests and Referrals: A Retrospective Cohort Study with Randomized Sampling.

Routine timely examinations of well-child health are important for achieving children's good health outcomes. Nevertheless, there is evidence of low compliance with well-child visit recommendations. The aim of the study was to examine potential factors associated with parents' nonadherence to routine childhood screening tests and their acting on further referrals following unusual findings. A retrospective cohort study was conducted among 14,348 children born in 2016-2017 and registered at mother-child health clinics in a large city in Israel. A sample of 844 children was randomly selected. Screening tests at the age of two months and nine months were examined. A multiple logistic regression examined potential factors associated with nonadherence to screening tests and to further referral for evaluation. Lower adherence to screening tests was found among parents of nine-month-old children, but adherence was higher for nurses' screening tests than for those of physicians. Children born in a complex delivery process, older mothers with a higher number of children, and Israeli citizens were at risk of not undergoing screening tests. Fewer children in the family and initial physician's findings were the only explanation for acting to referrals. In order to promote children's health outcomes and public health, health policymakers should conduct campaigns to convince parents of the importance of screening tests and of adherence to referrals with the aim of ensuring their children's wellbeing throughout the life cycle.

BNT162b2 mRNA COVID-19 vaccine booster induces seroconversion in patients with B-cell non-Hodgkin lymphoma who failed to respond to two prior vaccine doses.

This prospective study evaluated seroconversion rates in response to BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine booster in 44 B-cell non-Hodgkin lymphoma (B-NHL) patients who failed to respond to two prior doses [42 previously exposed to anti-CD20 monoclonal antibodies (moAbs) including 13 under maintenance treatment]. Seroconversion was obtained in 29.5% of the patients. Longer time from last anti-CD20 moAb (>6 months) and diagnosis of aggressive lymphoma compared to other, incurable B-NHLs were associated with increased seroconversion rates (47.8% vs.10.5%, p = 0.019 and 50% vs. 17.9%, p = 0.025 respectively). Thus, seronegative patients with B-NHL that completed anti-CD20 therapy more than 6 months prior to the booster have greater chances to achieve seroconversion.

The public's mixed emotional responses to violence directed at nurses: A mixed methods study.

AIMS AND OBJECTIVES: To understand whether exposure to an incident of violence directed at nurses, evoke among the public a sense of identification with the victim or with the perpetrator. BACKGROUND: Worldwide, evidence regarding workplace violence (WPV) in healthcare systems, explored the characteristics of the perpetrator, the healthcare settings and staff. Nevertheless, no studies examine the emotions of the public towards WPV in the healthcare systems. DESIGN: A convergent mixed method parallel design. METHODS: A structured questionnaire was distributed among 925 adults. Two scenarios were presented, with verbal and physical violence towards nurses. The participants rated how intensely they felt positive and negative emotions regarding the nurse and the perpetrator (quantitative stage). Sixty participants were also interviewed concerning their emotions regarding violence committed towards nurses (qualitative stage). Paired samples t-test were used to compare the emotions that were aroused regarding the perpetrator and the nurse. The effect size and Bonferroni correction for multiple comparisons were calculated. Constant comparative analysis method was used to analyzed the qualitative data. The STROBE checklist for cross-sectional studies and the COREQ guidelines for qualitative studies were used for reporting. RESULTS: Positive emotions were significantly higher towards the nurse than the perpetrator. Nevertheless, there were both positive and negative emotions towards the perpetrator and the nurse. The qualitative findings yielded two themes: (1) Mixed emotions towards the perpetrator, and (2) Mixed emotions towards the nurse. CONCLUSIONS: The public may emotionally identify with both the nurse and the perpetrator while positive and negative emotions are intertwined. Likewise, positive emotions are more intensely felt for the victims in both verbally and physically violent scenarios. RELEVANCE TO CLINICAL PRACTICE: These complemented findings highlight the need for campaigns promoting positive emotions toward healthcare professionals in an attempt to reduce and eliminate WPV in healthcare.

Extracellular Vesicles Derived from Chimeric Antigen Receptor-T Cells: A Potential Therapy for Cancer.

Chimeric antigen receptor (CAR)-T cells are genetically engineered T cells, directed against a tumor-associated antigen. Extracellular vesicles (EVs) derived from CAR-T cells (CAR-T EVs) may preserve CAR-T activity and overcome one of the major obstacles responsible for CAR-T cell failure in patients with solid tumors. This study aimed to compare CAR-T EVs with their parental cells and explore their cell penetration and cytotoxic activity. Anti-HER-2 CARs were stimulated with specific target cells. EVs were isolated from the cell media and characterized for their content and functions. We found that CAR-T EVs contained a mixture of small and large EVs. Stimulated anti-HER-2+ CAR-T EVs expressed lower cytokine levels compared with their parental CAR-T cells (such as interferon gamma). Higher levels of granzyme B were found in CAR-T EVs (≥20 × ) compared with EVs from unstimulated cells (p < 0.001). Anti-HER-2+ CAR-T EVs bound and penetrated specifically into HER-2 expressing target cells. Similar cytotoxic effects measured by caspase-3/7 activity were found in CAR-T cells and their derived EVs. However, while the CAR-T cells induced massive apoptosis during the first 24 h, CAR-T EVs required 60 - 90 h. In summary, CAR-T EVs provide a novel potent immunotherapy approach that may be effective against solid tumors.