A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloidderived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PDL1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

Overactive Bladder is a Distress Symptom in Heart Failure / 대한배뇨장애요실금학회지

The prevalence of Heart failure (HF) is expected to increase worldwide with the aging population trend. The numerous symptoms of and repeated hospitalizations for HF negatively affect the patient's quality of life and increase the patient's economic burden. Up to 50% of patients with HF suffer from urinary incontinence (UI) and an overactive bladder (OAB). However, there are limited data about the relationship between UI, OAB, and HF. The association between HF and urinary symptoms may be directly attributable to worsening HF pathophysiology. A comprehensive literature review was conducted for all publications between January 2000 and November 2017 using the PubMed, Embase, and Cochrane databases. HF represents a major and growing public health problem, with an increased risk of UI and an OAB as comorbidities. Possible effects of HF on urinary problems may be mediated by the prescription of medications for symptomatic relief. Although diuretics are typically used to relieve congestion, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve survival, these classes of drugs have been suggested to worsen urinary symptoms in the presence of HF. Further research is required to understand the impact of UI and an OAB on the HF illness trajectory.

Development of New Preventive and Therapeutic Vaccines for Tuberculosis

Tuberculosis (TB) is a contagious disease that has been responsible for the death of one billion people in the last 200 years. Until now, the only vaccine approved for the prevention of TB is Bacillus Calmette-Guérin (BCG), which is prepared by attenuating Mycobacterium bovis. However, one of the limitations of BCG is that its preventive effect against pulmonary TB varies from person to person. Therefore, there arises a need for a new TB vaccine to replace or supplement BCG. In this review, we have summarized the findings of current clinical trials on preventive and therapeutic TB vaccine candidates. In addition, we have discussed a novel vaccination approach using the cell-based vaccine presenting early secretory antigenic target-6 (ESAT-6), which is a potent immunogenic antigen. The role of ESAT-6 in hosts has also been described.

Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo

Chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (EV71) by suppressing viral 3C protease (3Cpro) activity. In the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus B3 (CVB3), which belongs to the same genus (Enterovirus) as EV71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. We found that chrysin showed antiviral activity against CVB3 at 10 muM, but exhibited mild cellular cytotoxicity at 50 muM, prompting us to synthesize derivatives of chrysin to increase the antiviral activity and reduce its cytotoxicity. Among four 4-substituted benzyl derivatives derived from C(5) benzyl-protected derivatives 7, 9-11 had significant antiviral activity and showed the most potent activity against CVB3 with low cytotoxicity in Vero cells. Intraperitoneal injection of CVB3 in BALB/c mice with 1x106 TCID50 (50% tissue culture infective dose) of CVB3 induced acute pancreatitis with ablation of acinar cells and increased serum CXCL1 levels, whereas the daily administration of 9 for 5 days significantly alleviated the pancreatic inflammation and reduced the elevation in serum CXCL1 levels. Collectively, we assessed the anti-CVB3 activities of chrysin and its derivatives, and found that among 4-substituted benzyl derivatives, 9 exhibited the highest activity against CVB3 in vivo, and protected mice from CVB3-induced pancreatic damage, simultaneously lowering serum CXCL1 levels.

Knowledge and Practice Behaviors Regarding Urinary Incontinence Among Korean Healthcare Providers in Long-term Care Hospitals / 대한배뇨장애요실금학회지

PURPOSE: The purpose of this study was to assess the current management status of patients with urological issues and to examine the level of knowledge and practice behaviors regarding urinary incontinence (UI) among Korean healthcare providers in long-term care hospitals. METHODS: This study used a cross-sectional descriptive design with a written questionnaire to assess knowledge and practice behaviors of 756 healthcare providers in 11 long-term care hospitals in Korean metropolitan areas. RESULTS: A total 42.6% of participants reported that more than 50% of patients had urologic issues, and that 68.1% of patients were regularly sent to urologists; no participants reported an on-site urologist in their facility. Participants identified collaboration with other hospitals and regular consultations by urologists as important factors in improving urologic care. Although the overall UI knowledge score was upper intermediate, a knowledge deficit was found for risk factors of UI. The knowledge level of physicians was significantly higher than that of other healthcare providers. Practice behaviors of nurses seemed to be better than those of other healthcare providers. CONCLUSIONS: Systematic collaboration between healthcare providers and urologic specialists, enhancing staff competence, and patient-tailored intervention should be recommended to improve quality of care for patients with urologic issues in long-term care hospitals.

Quality of Life of Women with Urinary Incontinence: A Systematic Literature Review / 대한배뇨장애요실금학회지

PURPOSE: The purpose of this study was to review studies that have examined the quality of life of women with urinary incontinence. MATERIALS AND METHODS: A review was conducted that used the databases PubMED, Proquest, CINAHL, and Sciencedirect. Articles were included that were published in English between 2005 and 2010 the key words use were urinary incontinence, women, and quality of life. RESULTS: A total of 18 studies were identified, and the prevalence of urinary incontinence varied depending on the definition of incontinence used and the age of the population studied. The Incontinence Quality of Life (I-QoL), Incontinence Impact Questionnaire-short form (IIQ-7), and King's Health Questionnaire (KHQ) were the most commonly used instruments. Demographic, medical, physical, psychological, health, and intervention factors were reported as influencing factors on the quality of life of women with incontinence. Age, severity of urinary incontinence, type of urinary incontinence, number of urinary incontinence episodes, body weight, stress, and help-seeking behavior were statistically significant variables influencing quality of life. CONCLUSION: Future studies are needed to identify factors related to quality of life among women with incontinence and to use validated instruments according to specific subjects.

The Effects of a Self-Management Program on Successful Aging

PURPOSE: The purpose of this study was to gain knowledge of successful aging for the Korean elderly and to identify the effects of an intervention program on the change of the knowledge. METHOD: Data were collected from 134 elders from 3 schools for the elderly in H City. The Successful Aging Scale was used to collect data and modified CDSMP was applied as the intervention. Descriptive statistics, t-test, ANOVA and ANCOVA were used. RESULTS: The total score of the knowledge of successful aging among the elderly cohort was 2.44 out of 3, and the scores of the factors making up old age were 2.66 for the success of children, 2.63 for self-control, 2.56 for self-efficacy, and 2.05 for happy marriage. Life satisfaction from the success of children and self-control were strongly correlated(r=0.7036, p=0.000). CONCLUSION: The self-management program brought positive changes to the knowledge of successful aging through the self-control parameter, and although it could not change the degree of knowledge of the overall successful aging among the elderly cohort, the program represents the first Korean nursing intervention focused on self-management techniques needed for successful aging.

Attitude, Beliefs, and Intentions to Care for SARS Patients among Korean Clinical Nurses: An Application of Theory of Planned Behavior / 간호학회지

PURPOSE: This study examined Korean clinical nurses' intentions to care for SARS patients and identify determinants of the intentions. Theory of planned behavior was the framework to explain the intentions of Korean nurses for SARS patients care. METHODS: A convenient sample of six hundreds and seventy nine clinical nurses from four university-affiliated hospitals located in Seoul and in Kyung-gi province was used. Self-administered (83-items) questionnaire was used to collect data. Intentions, attitude, subjective norm, perceive behavioral control, behavioral beliefs, normative beliefs, and control beliefs were the study variables. All items were measured using 7-point Likert scale (-3 to +3). Data were analyzed using descriptive statistics, Pearson correlation method, and stepwise multiple regression methods. RESULTS: Intentions and attitudes toward SARS patient care among Korean clinical nurses were moderate, but their subjective norm and perceive behavioral control of SARS patients care were negative. Stepwise multiple regression analysis indicated that attitude toward SARS patient care, perceived behavioral control, subjective norm were the determinants of the intentions for SARS patients care as theory proposed. Among the behavioral beliefs, "SARS-patient caring would be a new experience", "during SARS-patient caring, I should be apart from my family", "after completing SARS-patient caring, I would be proud of myself being able to cope with a stressful event" and "with my SARS-patient caring, patients could recover from SARS" were the significant determinants. Among the normative beliefs, colleague approval, spouse approval, and physician approval were significant determinants of the intentions. Among the control beliefs, "SARS-patient caring would be a challenge" "SARS-patient caring is a professional responsibility", "tension during the care of SARS patients" and "support from team members" were the significant determinants of the intentions. CONCLUSIONS: Korean clinical nurses in this study were not willing to care for SARS patients and showed negative attitude toward the care. They believed their friends and family were not approved their care for SARS patients. Nurses were in conflicts between professional responsibilities to care for SARS patients and personal safety. This study was the first to understand stress and burden of Korean clinical nurses who are in front line to care for newly developed communicable disease such as SARS. Under the circumstance where several fatal communicable diseases are predictable, conflicts between professional responsibility and their personal risks should be taken into considerations by nurses themselves and by nursing administrators in order to improve quality of care.

Validity and Reliability of an Instrument for Predictive Nursing Intention for SARS Patient Care / 간호학회지

PURPOSE: This study was done to develop and test validity and reliability of on instrument for predicting nursing intention for SARS patient care. METHOD: The psychometric properties of a SARS patient care attrition prediction tool, based on the Theory of Planned Behavior, were examined in this study. The Three-phase design involved a) salient beliefs generated from clinical nurses (n=43) b) content validation by expert panel evaluations(n=5) c) face validation by plot testing (n=10) d) and instrument validation in a cross sectional survey (n=299). Psychometric analysis of survey data provided empirical evidence of the construct validity and reliability of the instrument. RESULT: Principal component analysis verified the hypothesized 6-factor solution, explaining 68.2% of variance, and Alpha coefficients of .7538 to .9389 indicated a high internal consistency of the instrument. CONCLUSION: The instrument can be used by nurse administrators and researcher to assess clinical nurses' salient beliefs about caring for SARS patients, guide tailored intervention strategies to effective caring, and evaluate the effectiveness of interventions.

A Development of Nursing Outcome Indicators for Stroke Patients / 성인간호학회지

PUPPOSE: This study was conducted to develop nursing outcome indicators based on nursing activities done for stroke patients. METHOD: focus group meeting and delphi technique, which consisted of clinical nurse experts, neurologist, and nursing professors. CVI(Index of Content Validity) and user validity test was performed. RESULT: 12 nursing diagnoses, 29 nursing interventions and nursing outcomes were identified. The former were from NIC and the latter were developed according to nursing interventions. They were verified by experts in focus group. 199 nursing activities were identified, 133 nursing outcome indicators were developed. In user validity, usefulness and usability were tested. CONCLUSION: This systemic approach of measuring nursing outcomes verified nurses' positive effects in changing patients health status and nursing contributions in the health care system as a profession.

Factors Influencing Functional Status in People with Chronic Lung Disease / 간호학회지

PURPOSE: The purpose of this study was to identify factors that influence the functional status of chronic lung disease patients. METHOD: A descriptive, correlational study design was used. The study was conducted at the outpatient respiratory clinic of the large university hospital in Korea. A convenience sample of 128 chronic lung patients (age = 64.2 yrs; 106 COPD, 17 bronchiectasis, 5 DILD) with mean FEV1 64.4 % predicted. Functional status was measured with SIP. Physical variables (FEV1% predicted, dyspnea, fatigue, pulmonary symptom distress), psychological variables (mood, stress), and situational variable (sleep quality) were examined. Dyspnea was measured by the BDI, fatigue was measured with the MFI. Mood was measured with the modified Korean version of POMS. Sleep quality was measured with the Pittsburgh Sleep Quality Index. Potential independent variables for the regression were age, gender, years since diagnosis, FEV1% predicted, dyspnea, fatigue, pulmonary symptom distress, stress, and sleep quality. RESULT: In general, functional status was relatively good. In regression analysis, functional status were significantly influenced by dyspnea, mood, age and fatigue. These variables explained 70 % of the variances in functional status. CONCLUSION: The results suggest that psychophysiologic symptom management should be a focus to enhance the functional status in this group.

The Effect of Preceptorship on Clinical Education of Nursing Students / 성인간호학회지

This study examined effect of preceptorship on clinical education of senior nursing students of Y. University in Seoul. Quasi-experimental study design was used. Sixty students of pre-test and 80 of post-test participated in this study. Competency scores of the students before the clinical education(pre-competency scores) were compared with the competency scores after the clinical education(post-competency scores), and teacher evaluation scores between preceptors and clinical the data from students with preceptors(experimental group, N=22) and with clinical instructors(comparative group, N=58) were also examined. Study results indicated that the total post-competency scores were higher compared to the total pre-competency scores, and the difference was statistically significant. Among 7 sub-domains, differences were all statistically significant in 6 sub-domains except "self-esteem" domain. Competency scores of the students who had clinical education with had clinical education from clinical instructors. But the difference between those scores was not statistically significant. However, students gave higher evaluation scores to preceptors than clinical instructors. This study concluded that preceptorship did not influence much on clinical education at this time yet. However it is expected that when preceptors adjust their new roles and function them in expert education. This study recommended that for the preceptors to increase their motivation to teach students and to accept their roles, systemic rewards are needed.