An Update of Gonadotropin-Releasing Hormone Antagonists in the Treatment of Advanced Prostate Cancer

For decades, androgen deprivation therapy (ADT) was the cornerstone treatment for advanced prostate cancer. ADT using gonadotropin-releasing hormone (GnRH) agonist or antagonist acts by blocking the hypothalamic-pituitary-gonadal system with different mechanism. Both injectable GnRH agonist and antagonist are currently used as a standard of care. The novel oral GnRH antagonist has recently approved and it may have a promising alternative to the conventional ADT. This review will focus on the history of drug development, efficacy and safety profiles for GnRH antagonists in patients with prostate cancer.

An Update of Gonadotropin-Releasing Hormone Antagonists in the Treatment of Advanced Prostate Cancer

For decades, androgen deprivation therapy (ADT) was the cornerstone treatment for advanced prostate cancer. ADT using gonadotropin-releasing hormone (GnRH) agonist or antagonist acts by blocking the hypothalamic-pituitary-gonadal system with different mechanism. Both injectable GnRH agonist and antagonist are currently used as a standard of care. The novel oral GnRH antagonist has recently approved and it may have a promising alternative to the conventional ADT. This review will focus on the history of drug development, efficacy and safety profiles for GnRH antagonists in patients with prostate cancer.

Dust particles-induced intracellular Ca²⁺ signaling and reactive oxygen species in lung fibroblast cell line MRC5

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established Ca²⁺ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular Ca²⁺ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular Ca²⁺ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than 10 µm, induced intracellular Ca²⁺ signaling, which was mediated by extracellular Ca²⁺. The PM10-mediated intracellular Ca²⁺ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

Effects of Overactive Bladder Symptoms in Stroke Patients' Health Related Quality of Life and Their Performance Scale

OBJECTIVE: To identify the effects of overactive bladder (OAB) symptoms on the health-related quality of life (HRQOL) in stroke patients since OAB symptoms are common in such patients, but their effects on stroke rehabilitation over time are unclear. METHODS: This study included 30 post-acute stroke patients who had been admitted for rehabilitation treatments. All participants completed a questionnaire evaluating urinary symptoms, including the Overactive Bladder Symptom Score (OABSS) and general HRQOL with a Short-Form 36 (SF-36) health survey. We assessed their performance in terms of the Function Ambulation Category, Modified Rankin Scale (MRS), Modified Barthel Index, and Mini-Mental State Examination (MMSE). All assessments were carried out twice at baseline and at 3 months. We divided patients into an OAB and non-OAB group with OABSS. A correlation analysis and multivariate regression were then performed. RESULTS: All performance scales showed an improvement over 3 months in the non-OAB group (n=18; p < 0.02), but, MRS and MMSE scores did not improve significantly in the OAB group (n=12) (p=0.15 and p=0.20, respectively). In the OAB group, the vitality and mental health scores significantly decreased over 3 months (p=0.011 and p=0,041, respectively), and the mental component summary (MCS) score showed a marginal decrease over 3 months (p=0.05). A multivariate regression analysis revealed that OAB symptoms were negatively correlated with the 3 months MCS score (B=−8.15, p=0.034). CONCLUSION: These results indicated that OAB symptoms could have negative effects on HRQOL and performance in patients suffering from a stroke.

Effects of Overactive Bladder Symptoms in Stroke Patients' Health Related Quality of Life and Their Performance Scale

OBJECTIVE: To identify the effects of overactive bladder (OAB) symptoms on the health-related quality of life (HRQOL) in stroke patients since OAB symptoms are common in such patients, but their effects on stroke rehabilitation over time are unclear. METHODS: This study included 30 post-acute stroke patients who had been admitted for rehabilitation treatments. All participants completed a questionnaire evaluating urinary symptoms, including the Overactive Bladder Symptom Score (OABSS) and general HRQOL with a Short-Form 36 (SF-36) health survey. We assessed their performance in terms of the Function Ambulation Category, Modified Rankin Scale (MRS), Modified Barthel Index, and Mini-Mental State Examination (MMSE). All assessments were carried out twice at baseline and at 3 months. We divided patients into an OAB and non-OAB group with OABSS. A correlation analysis and multivariate regression were then performed. RESULTS: All performance scales showed an improvement over 3 months in the non-OAB group (n=18; p < 0.02), but, MRS and MMSE scores did not improve significantly in the OAB group (n=12) (p=0.15 and p=0.20, respectively). In the OAB group, the vitality and mental health scores significantly decreased over 3 months (p=0.011 and p=0,041, respectively), and the mental component summary (MCS) score showed a marginal decrease over 3 months (p=0.05). A multivariate regression analysis revealed that OAB symptoms were negatively correlated with the 3 months MCS score (B=−8.15, p=0.034). CONCLUSION: These results indicated that OAB symptoms could have negative effects on HRQOL and performance in patients suffering from a stroke.

Very Late Onset of Radiation-induced Complicated Vesicocutaneous Fistula

Vesicocutaneous fistula (VCF) secondary to radiation therapy is a rare event. There are difficulties in establishing the early diagnosis and choosing the proper management option. We present a very unusual case of postradiotherapy vesicocutaneous fistula which developed more than 30 years later. Temporary urinary diversion was performed because of poor performance status and anatomical condition. However, it failed to achieve spontaneous closure of VCF. It is important to recognize that late onset of radiation induced VCF could develop even after a substantial period of time has lapsed. In addition, conservative treatment appears to be unsuccessful in patient with complicated VCF. Therefore, it must be counselled carefully after a making synthetic judgment based on different individual situation.

Effect of curcumin on the interaction between androgen receptor and Wnt/beta-catenin in LNCaP xenografts

PURPOSE: Curcumin is a nontoxic, chemopreventive agent possessing multifaceted functions. Our previous study showed that curcumin inhibits androgen receptor (AR) through modulation of Wnt/beta-catenin signaling in LNCaP cells. Therefore, we investigated the in vivo effects of curcumin by using LNCaP xenografts. MATERIALS AND METHODS: LNCaP cells were subcutaneously inoculated in Balb/c nude mice. When the tumor volume reached greater than 100 mm3, either curcumin (500 mg/kg body weight) or vehicle was administered through oral gavage three times weekly for 4 weeks. The expression of AR and intermediate products of Wnt/beta-catenin were assessed. RESULTS: Curcumin had an inhibitory effect on tumor growth during the early period, which was followed by a slow increase in growth over time. Tumor growth was delayed about 27% in the curcumin group. The mean prostate-specific antigen (PSA) doubling time in the curcumin group was approximately twice that in the untreated group. Curcumin significantly decreased AR expression at both the mRNA and protein level. The PSA levels tended to be reduced in the curcumin group. However, there were no significant changes in expression of Wnt/beta-catenin pathway intermediates. CONCLUSIONS: This study revealed that curcumin initially interferes with prostate cancer growth by inhibiting AR activity and possibly by reducing PSA expression. Further research is needed to investigate the plausible mechanism of the antiandrogenic action of curcumin.

Bacterial PAMPs and Allergens Trigger Increase in Ca2+i-induced Cytokine Expression in Human PDL Fibroblasts

An oral environment is constantly exposed to environmental factors and microorganisms. The periodontal ligament (PDL) fibroblasts within this environment are subject to bacterial infection and allergic reaction. However, how these condition affect PDL fibroblasts has yet to be elucidated. PDL fibroblasts were isolated from healthy donors. We examined using reverse transcription-polymerase chain reaction and measuring the intracellular Ca2+ concentration ([Ca2+]i). This study investigated the receptors activated by exogenous bacterial pathogens (Lipopolysaccharide and peptidoglycan) and allergens (German cockroach extract and house dust mite) as well as these pathogenic mediators-induced effects on the intracellular Ca2+ signaling in human PDL fibroblasts. Moreover, we evaluated the expression of pro-inflammatory cytokines (interleukin (IL)-1beta, IL-6, and IL-8) and bone remodeling mediators (receptor activator of NF-kappaB ligand and osteoprotegerin) and intracellular Ca2+-involved effect. Bacterial pathogens and allergic mediators induced increased expression of pro-inflammatory cytokines, and these results are dependent on intracellular Ca2+. However, bacterial pathogens and allergic mediators did not lead to increased expression of bone remodeling mediators, except lipopolysaccharide-induced effect on receptor activator of NF-kappaB ligand expression. These experiments provide evidence that a pathogens and allergens-induced increase in [Ca2+]i affects the inflammatory response in human PDL fibroblasts.

Dexmedetomidine Modulates Histamine-induced Ca2+ Signaling and Pro-inflammatory Cytokine Expression

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing alpha2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca2+ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced Ca2+ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger Ca2+ peak or increase in the presence or absence of external Ca2+. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca2+]i signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca2+ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

Peptidoglycan Induces the Production of Interleukin-8 via Calcium Signaling in Human Gingival Epithelium

The etiology of periodontal disease is multifactorial. Exogenous stimuli such as bacterial pathogens can interact with toll-like receptors to activate intracellular calcium signaling in gingival epithelium and other tissues. The triggering of calcium signaling induces the secretion of pro-inflammatory cytokines such as interleukin-8 as part of the inflammatory response; however, the exact mechanism of calcium signaling induced by bacterial toxins when gingival epithelial cells are exposed to pathogens is unclear. Here, we investigate calcium signaling induced by bacteria and expression of inflammatory cytokines in human gingival epithelial cells. We found that peptidoglycan, a constituent of gram-positive bacteria and an agonist of toll-like receptor 2, increases intracellular calcium in a concentration-dependent manner. Peptidoglycan-induced calcium signaling was abolished by treatment with blockers of phospholipase C (U73122), inositol 1,4,5-trisphosphate receptors, indicating the release of calcium from intracellular calcium stores. Peptidoglycan-mediated interleukin-8 expression was blocked by U73122 and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). Moreover, interleukin-8 expression was induced by thapsigargin, a selective inhibitor of the sarco/endoplasmic reticulum calcium ATPase, when thapsigargin was treated alone or co-treated with peptidoglycan. These results suggest that the gram-positive bacterial toxin peptidoglycan induces calcium signaling via the phospholipase C/inositol 1,4,5-trisphosphate pathway, and that increased interleukin-8 expression is mediated by intracellular calcium levels in human gingival epithelial cells.

Missed Spermatic Cord Torsion in an Old Man

The fate of testicular salvage in spermatic cord torsion depends on the duration of ischemia and the degree of torsion. Even though spermatic cord torsion (SCT) can occur at any age, it is rarely reported in older patients. If the physician does not pay close attention to this unusual situation, the lack of suspicion for SCT may result in a missed or delayed diagnosis. We report a very uncommon case of missed SCT occurring in a 63-year-old man.

Atypical Epidermoid Cyst in Renal Pelvis and Histogenetic Implications / 대한배뇨장애요실금학회지

Since the renal epidermoid cyst is too rare, the mechanisms of squamous morphogenesis have not well characterized. A 73-year-old female was referred with an incidentally detected renal pelvis mass. Abdominopelvic computed tomography scan revealed a noncalcified soft tissue mass in the renal pelvis. Total nephroureterectomy was performed under the impression of a renal pelvis malignancy. The patient was discharged without postoperative complication. The outer surface of mass lesion was lined with urothelia and squamous epithelia, containing keratinous materials. The urothelia were positively stained against uroplakin II and cytokeratin 7, whereas almost of the squamous epithelia were negative with uroplakin II. The two different epithelia were generally sharply demarcated. Interestingly, some part of squamous epithelia contained uroplakin-positive and many more cytokeratin 7-positive cells. The atypical clinical features in our case can reconsider the diagnostic clues of renal epidermoid cysts that have been reported before, and the unique immunohistochemical results may understand the histogenetic implications of the lesion.

Can 80 W KTP Laser Vaporization Effectively Relieve the Obstruction in Benign Prostatic Hyperplasia?: A Nonrandomized Trial

PURPOSE: There is little data evaluating the changes of severity of bladder outlet obstruction after 80 W-potassium-titanyl-phosphate (KTP) photoselective laser vaporization prostatectomy (PVP) by pressure-flow study. We evaluated the efficacy of PVP to relieve the obstruction in benign prostate hyperplasia (BPH) compared with transurethral resection of the prostate (TURP). MATERIALS AND METHODS: This is a prospective, non-randomized single center study. The inclusion criteria were as follows: Men suffering from lower urinary tract symptoms (LUTS) secondary to BPH, age > or =50 years, International Prostatic Symptom Score (IPSS) > or =13, maximum flow rate (Qmax) or =40 was decreased from 64% to 4% in the PVP group and from 86% to 14% in the TURP group. CONCLUSIONS: PVP could reduce the prostate volume effectively and relieve bladder outlet obstruction similar to TURP by the 6-month follow up in men with BPH.

Long-Term Results of Laparoscopic Burch Colposuspension for Stress Urinary Incontinence in Women

We evaluated the long-term efficacy of laparoscopic Burch colposuspension for stress urinary incontinence (SUI) in women. A total of 68 patients who underwent extraperitoneal laparoscopic Burch colposuspensions with more than a 3-yr follow-up were included. The colposuspension was performed by using two non-absorbable sutures on each side. The patients were considered to be cured of SUI if they had a negative result of cough stress test and there were no reports of urine leakage during physical stress. The mean follow-up period was 52 months (range, 36 to 83 months). The overall subjective cure rate was reported in 49 patients (72%). There was no significant difference between the cured and non-cured group in terms of clinical parameters. The cure rate tended to decline gradually over time and it was more deteriorated significantly after 4 yr of surgery. Based on these results, we recommend that long-term follow-up is needed when evaluating the clinical efficacy of anti-incontinence surgery.

Alteration of Expression of Ca(2+) Signaling Proteins and Adaptation of Ca(2+) Signaling in SERCA2(+/-) Mouse Parotid Acini

PURPOSE: The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), encoded by ATP2A2, is an essential component for G-protein coupled receptor (GPCR)-dependent Ca(2+) signaling. However, whether the changes in Ca(2+) signaling and Ca(2+) signaling proteins in parotid acinar cells are affected by a partial loss of SERCA2 are not known. MATERIALS AND METHODS: In SERCA2(+/-) mouse parotid gland acinar cells, Ca(2+) signaling, expression levels of Ca(2+) signaling proteins, and amylase secretion were investigated. RESULTS: SERCA2(+/-) mice showed decreased SERCA2 expression and an upregulation of the plasma membrane Ca(2+) ATPase. A partial loss of SERCA2 changed the expression level of 1, 4, 5-tris-inositolphosphate receptors (IP(3)Rs), but the localization and activities of IP3Rs were not altered. In SERCA2(+/-) mice, muscarinic stimulation resulted in greater amylase release, and the expression of synaptotagmin was increased compared to wild type mice. CONCLUSION: These results suggest that a partial loss of SERCA2 affects the expression and activity of Ca(2+) signaling proteins in the parotid gland acini, however, overall Ca(2+) signaling is unchanged.

Proteomic Analysis of the Proteins That were Changed by Bilateral Orchiectomy in the Rabbit Corpus Cavernosum / 대한비뇨기과학회지

PURPOSE: The pathophysiological role of androgen deprivation in male sexual dysfunction remains controversial, and this is especially true at the molecular level. We investigated the effect of androgen deprivation on the changes of proteins in the penile corpus cavernosum of castrated rabbits by the proteomic approach. MATERIALS AND METHODS: New Zealand white male rabbits(2.5-3kg) were divided into 2 groups: the control group with 5 rabbits and the bilateral orchiectomized group. The bilateral orchiectomized group was divided into the post-operative 4 weeks group(group 1), and the 8 weeks group (group 2) with 5 rabbits in groups 1 and 2, respectively. The penile corpus cavernosum was partly excised at 4 or 8 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-D gel electrophoresis; this was followed by computational image analysis and protein identification with using mass spectrometry. RESULTS: A comparison of the corpus cavernosum of the orchiectomized group with the control group showed that nine proteins had a changed expression. Glycerol-3-phosphate dehydrogenase and F-actin binding protein were under-expressed in groups 1 and 2, and myosin regulatory light chain 2, tropomyosin beta chain and tropomyosin 1 were significantly under- expressed in group 1 and they were insignificantly over-expressed in group 2. In addition there were 4 proteins that were insignificantly under- expressed; skeletal muscle myosin heavy chain MyHC-EO/III, a protein that was similar to suppressor of cytokine signaling 6 isoform, myosin light chain 1 and heat shock 27kDa protein 1. CONCLUSIONS: This data suggests that changes of proteins, and especially tropomyosin 1, mean there is processing of the cellular apoptosis pathway in the orchiectomized rabbits' corpus cavernosum. However more information is needed about human corpus cavernosal tissue.

Proteomic Analysis of the Proteins That were Changed by Bilateral Orchiectomy in the Rabbit Corpus Cavernosum / 대한비뇨기과학회지

PURPOSE: The pathophysiological role of androgen deprivation in male sexual dysfunction remains controversial, and this is especially true at the molecular level. We investigated the effect of androgen deprivation on the changes of proteins in the penile corpus cavernosum of castrated rabbits by the proteomic approach. MATERIALS AND METHODS: New Zealand white male rabbits(2.5-3kg) were divided into 2 groups: the control group with 5 rabbits and the bilateral orchiectomized group. The bilateral orchiectomized group was divided into the post-operative 4 weeks group(group 1), and the 8 weeks group (group 2) with 5 rabbits in groups 1 and 2, respectively. The penile corpus cavernosum was partly excised at 4 or 8 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-D gel electrophoresis; this was followed by computational image analysis and protein identification with using mass spectrometry. RESULTS: A comparison of the corpus cavernosum of the orchiectomized group with the control group showed that nine proteins had a changed expression. Glycerol-3-phosphate dehydrogenase and F-actin binding protein were under-expressed in groups 1 and 2, and myosin regulatory light chain 2, tropomyosin beta chain and tropomyosin 1 were significantly under- expressed in group 1 and they were insignificantly over-expressed in group 2. In addition there were 4 proteins that were insignificantly under- expressed; skeletal muscle myosin heavy chain MyHC-EO/III, a protein that was similar to suppressor of cytokine signaling 6 isoform, myosin light chain 1 and heat shock 27kDa protein 1. CONCLUSIONS: This data suggests that changes of proteins, and especially tropomyosin 1, mean there is processing of the cellular apoptosis pathway in the orchiectomized rabbits' corpus cavernosum. However more information is needed about human corpus cavernosal tissue.

The Effect of Bethanechol Chloride with an alpha-adrenergic Blocker in Patients with Impaired Detrusor Contractility / 대한비뇨기과학회지

PURPOSE: Bethanechol enhances detrusor contraction and alpha1-blockers reduce bladder outlet resistance. We evaluated the effects of bethanechol with doxazosin in patients with impaired detrusor contractility. MATERIALS AND METHODS: Fifty-six patients that had confirmed detrusor underactivity with at least 150ml of postvoid residual urine volume(PVR) based on a urodynamic study were enrolled. The initial dosage of bethanechol given was 75mg/day, and the dosage was gradually increased to 150mg/day if necessary. Doxazosin gastro-intestinal therapeutic system(GITS)(4mg) was also given. The effect of the treatment was evaluated by a urine flow test, the amount of PVR, and frequency of clean intermittent catheterization(CIC). RESULTS: The mean follow-up period was 6 months(range, 1 to 9 months). After treatment, the mean PVR decreased from 251.8+/-149.6ml to 136.4+/-153.2ml(p<0.001) and was less than 100ml in 22(39%) of the 38 patients that showed a decrease. The maximum flow rate(Qmax) increased from 8.7+/-4.7ml/s to 11.1+/-5.6ml/s(p=0.024) and was more than 5ml/s in 13 patients(23%). Five of the 18 patients that previously required CIC could discontinue this treatment and another nine patients showed a decrease in the frequency. The mean daily frequency of CIC was reduced from 3.2 to 1.5(p=0.004). Ten of the 12 patients that were not able to void became capable of voluntary voiding. Five patients(9%) complained of adverse reactions and four of them were taken off the medication. CONCLUSIONS: The combination therapy of bethanechol with doxazosin improved emptying ability in patients with impaired detrusor contractility.

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) Scales in Men with Prostate Cancer: Reliability and Validity of the Korean Version

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire is a relevant, worldwide tool used for assessing the health-related quality of life in men with prostate cancer. The purpose of this study was to translate the FACT-P into Korean, to assess its reliability and validity, and to test its discriminative ability between the cancer patients and normal controls. The Korean version was developed via the FACT multilingual translation project. The translated questionnaire was self-administered to 70 prostate cancer patients and 70 age-matched controls. In evaluating its psychometric properties for cancer patients, internal consistency and test-retest reliability were used. Validity was estimated by using inter-subscale correlations and discriminant validity between cancer patients and controls. Cronbach's alpha coefficient for the individual subscales were 0.7 or greater (range 0.73 to 0.89), except for emotional well-being (0.61). The test-retest reliability showed high correlations (intraclass coefficients ranged from 0.72 to 0.93). Inter-subscale correlations demonstrated each subscale was unrelated, but moderate correlation was observed between social/family well-being and functional well-being subscales (r=0.56). The FACT-P scale could discriminate reliably between the cancer patients and controls in most subscales. In conclusion, the Korean version of the FACT-P is a reliable and valid questionnaire in patients with prostate cancer.

A Review Study on the Strategies for Concept Analysis / 간호학회지

PURPOSE: Concept analysis is an essential part of theory development in nursing. Thus, many strategies or methods of concept analysis have been suggested in nursing literature. However, in Korea, only limited strategies were utilized, without much consideration on a wide range of strategies in choosing a method that coincides with the characteristics of each concept to analyze. The purpose of this article was to propose various strategies for concept analysis. METHOD: A literature review method was used. RESULT: Ten methods of concept analysis were identified in the literature, and they were evaluated for advantages and limitations. In addition to the method by Walker and Avant and a hybrid model, more advanced strategies, such as triangulation method, critical analysis and the feminist approach were introduced and described in detail. The examples used in each concept analysis method were presented in table to provide the extent of utilization of each method. CONCLUSION: This article provides a wide range of strategies in identifying, clarifying, or elaborating a concept. It might help in choosing a method that best fits the concept to analyze, thus enhancing quality of concept analysis research.