Conducting and Writing Quantitative and Qualitative Research.

Comprehensive knowledge of quantitative and qualitative research systematizes scholarly research and enhances the quality of research output. Scientific researchers must be familiar with them and skilled to conduct their investigation within the frames of their chosen research type. When conducting quantitative research, scientific researchers should describe an existing theory, generate a hypothesis from the theory, test their hypothesis in novel research, and re-evaluate the theory. Thereafter, they should take a deductive approach in writing the testing of the established theory based on experiments. When conducting qualitative research, scientific researchers raise a question, answer the question by performing a novel study, and propose a new theory to clarify and interpret the obtained results. After which, they should take an inductive approach to writing the formulation of concepts based on collected data. When scientific researchers combine the whole spectrum of inductive and deductive research approaches using both quantitative and qualitative research methodologies, they apply mixed-method research. Familiarity and proficiency with these research aspects facilitate the construction of novel hypotheses, development of theories, or refinement of concepts.

Quercetin-Induced Enhancement of Nasal Epithelial Cells' Ability to Produce Clara Cell 10-kD Protein In Vitro and In Vivo.

Background: Quercetin, a polyphenolic flavonoid found in various plants and foods, is known to have antioxidant, antiviral and anticancer effects. Although quercetin is well known to exert anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modifies the clinical status of allergic diseases, such as allergic rhinitis (AR), remain unclear. The present study examined whether quercetin could modulate the production of the endogenous anti-inflammatory molecule, Clara cell 10-kD protein (CC10), in vitro and in vivo. Methods: Human nasal epithelial cells (1 × 105 cells/mL) were stimulated with 20 ng/mL of tumor necrosis factor-alpha (TNF) in the presence of quercetin for 24 h. CC10 levels in culture supernatants were examined by ELISA. Sprague Dawley rats were sensitised with toluene 2,4-diisocyanate (TDI) by intranasal instillation of 10% TDI in ethyl acetate at a volume of 5.0 µL once daily for five days. This sensitisation procedure was repeated after an interval of two days. The rats were treated with different dosages of quercetin once daily for five days starting on the 5th day following the second sensitization. Nasal allergy-like symptoms induced by the bilateral application of 5.0 µL of 10% TDI were assessed by counting sneezing and nasal-rubbing behaviours for 10 min immediately after the TDI nasal challenge. The levels of CC10 in nasal lavage fluids obtained 6 h after TDI nasal challenge were examined using ELISA. Results: The treatment of cells with low doses of quercetin (<2.5 µM) scarcely affected TNF-induced CC10 production from nasal epithelial cells. However, the ability of nasal epithelial cells to produce CC10 after TNF stimulation significantly increased on treatment with quercetin doses (>5.0 µM). The oral administration of quercetin (>25 mg/kg) for five days significantly increased the CC10 content in nasal lavage fluids and attenuated the nasal symptoms induced by the TDI nasal challenge. Conclusions: Quercetin inhibits AR development by increasing the ability of nasal epithelial cells to produce CC10.

Inhibition of Angiogenic Factor Productions by Quercetin In Vitro and In Vivo.

Background: Angiogenesis is well known to be an important event in the tissue remodeling observed in allergic diseases. Although there is much evidence that quercetin, one of the most abundant dietary flavonoids, exerts anti-allergic effects in both human and experimental animal models of allergic diseases, the action of quercetin on angiogenesis has not been defined. Therefore, in this study, we first examined the action of quercetin on the secretion of angiogenic factors from murine mast cells in vitro. We also examined the action of quercetin on angiogenic factor secretion in the murine allergic rhinitis model in vivo. Methods: Mast cells (1 × 105 cells/mL) sensitized with ovalbumin (OVA)-specific murine IgE were stimulated with 10.0 ng/mL OVA in the presence or the absence of quercetin for 24 h. The concentrations of angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-α, IL-6 and IL-8 in the supernatants were examined by ELISA. BALB/c male mice immunized with OVA were challenged intranasally with OVA every other day, starting seven days after the final immunization. These mice were then orally administered quercetin once a day for five days, starting seven days after the final immunization. Clinical symptoms were assessed by counting the number of sneezes and nasal rubbing behaviors during the 10 min period just after OVA nasal provocation. The angiogenic factor concentrations in the nasal lavage fluids obtained 6 h after nasal antigenic provocation were examined by ELISA. Results: Quercetin significantly inhibited the production of angiogenetic factors induced by IgE-dependent mechanisms at 5.0 µM or more. Oral administration of 25.0 mg/kg quercetin into the mice also suppressed the appearance of angiogenetic factors in nasal lavage fluids, along with the attenuation of nasal symptoms. Conclusions: These results strongly suggest that the inhibitory action of quercetin on angiogenic factor secretion may be implicated in the therapeutic action of quercetin on allergic diseases, especially allergic rhinitis.

Factors associated with the mental health status of medical students during the COVID-19 pandemic: a cross-sectional study in Japan.

OBJECTIVE: The COVID-19 pandemic had a substantial impact on university students, including those in medical schools, with disruption in routine education causing significant psychological distress. The objective of this study was to evaluate the factors associated with psychological distress among medical students during the period of enforced home quarantine from March through May 2020. DESIGN: A cross-sectional study. SETTING: One Japanese medical school. PARTICIPANTS: 571 medical students. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-administered electronic questionnaires including the K-6 scale for psychological distress, the Rosenberg Self-Esteem Scale (RSES) for self-esteem and the General Self-Efficacy Scale (GSES) for self-efficacy were distributed. To assess the determinant factor for psychological distress, variables such as sex, grade in school, living conditions, and RSES and GSES scores were evaluated in regression analysis. RESULTS: 163 respondents (28.5%) scored ≥5 on the K-6 scale, indicating a significant degree of psychological distress. Logistic regression revealed that a higher score on RSES (p<0.001) and GSES (p<0.01) was an independent factor associated with lower levels of psychological distress. Multiple regression analysis focusing on students with a K-6 score ≥5 revealed that higher scores on RSES correlated with lower levels of psychological distress. By contrast, those with higher GSES scores also scored higher for indicators of psychological distress. CONCLUSIONS: This study identified that self-efficacy and self-esteem were both influential factors for predicting psychological distress during the current COVID-19 pandemic. Medical schools should provide support for mental health and educational initiatives directed at enhancing self-esteem and self-efficacy, with a focus on improving personal resilience. In emergency situations, such as that faced in response to the COVID-19 pandemic, initial programmes might target students with higher levels of self-efficacy. By contrast, under routine situations, these efforts should be directed towards students with lower self-esteem as primary means to prevent depression.

Modulation of Th1/Th2 Cytokine Balance by Quercetin In Vitro.

Background: Allergic rhinitis (AR) is well known to be an IgE-mediated chronic inflammatory disease in the nasal wall, which is primarily mediated by Th2-type cytokines such as IL-4, IL-5, and IL-13. Although quercetin is also accepted to attenuate the development of allergic diseases such as AR, the influence of quercetin on Th2-type cytokine production is not well understood. The present study was designed to examine whether quercetin could attenuate the development of AR via the modulation of Th2-type cytokine production using an in vitro cell culture technique. Methods: Human peripheral-blood CD4+ T cells (1 × 106 cells/mL) were cultured with 10.0 ng/mL IL-4 in the presence or absence of quercetin. The levels of IL-5, IL-13, and INF-γ in 24 h culture supernatants were examined by ELISA. The influence of quercetin on the phosphorylation of transcription factors NF-κB and STAT6, and mRNA expression for cytokines were also examined by ELISA and RT-PCR, respectively. Results: Treatment of cells with quercetin at more than 5.0 µM inhibited the production of IL-5 and IL-13 from CD4+ T cells induced by IL-4 stimulation through the suppression of transcription factor activation and cytokine mRNA expression. On the other hand, quercetin at more than 5.0 µM abrogated the inhibitory action of IL-4 on INF-γ production from CD4+ T cells in vitro. Conclusions: The immunomodulatory effects of quercetin, especially on cytokine production, may be responsible, in part, for the mode of therapeutic action of quercetin on allergic diseases, including AR.

Clinical practice guidelines for the management of olfactory dysfunction - Secondary publication.

OBJECTIVE: To provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society. METHODS: Seven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were "smell disorder," "olfactory dysfunction," "olfactory loss," "olfactory disturbance," "olfactory impairments," "olfaction disorder," "smell disorder," "anosmia," "cacosmia," and "dysosmia." Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A-strongly recommended to D-not recommended, were adopted for the management of olfactory dysfunction. RESULTS: Both oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by randomized-controlled trials (RCTs) or placebo-controlled trials, olfactory training using odorants has been reported to be effective for improving olfactory function. There is considerable evidence that olfactory testing is useful for differential diagnosis, prediction of disease progression, and early detection of cognitive decline in neurodegenerative diseases. CONCLUSION: The Clinical Practice Guideline has developed recommendations for the management of various aspects of olfactory dysfunction.

Inhibitory action of levocetirizine on the production of eosinophil chemoattractants RANTES and eotaxin in vitro and in vivo.

Eosinophils are well known to play essential roles in the development and maintenance of allergic diseases. However, the influence of histamine H1 receptor antagonists on eosinophil functions, especially chemokine production, are not well-defined. Therefore, in the present study, we examined the influence of histamine H1 receptor antagonist on chemokine production by eosinophils through the use of levocetirizine in vitro and in vivo. Eosinophils prepared from mice were stimulated with specific antigens in the presence of different concentrations of levocetirizine. After 24 h, regulated on activation normal T cell expressed and secreted (RANTES) and eotaxin levels in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Patients with Japanese cedar pollinosis were treated with 5 mg levocetirizine once a day for four weeks during the pollen season (February 2012 to April 2012). RANTES and eotaxin levels in nasal secretions were also examined by ELISA. The addition of levocetirizine to eosinophil cultures caused a dose-dependent decrease in the ability of cells to produce RANTES and eotaxin in response to antigen stimulation, and the minimum concentration that caused a significant decrease was 0.05 µM. Although cetirizine also exerted suppressive effects on the production of RANTES and eotaxin by eosinophils, the minimum concentration that caused significant suppression was 0.15 µM, which was three-times higher than that of levocetirizine. Oral administration of levocetirizine for four weeks also reduced RANTES and eotaxin levels in nasal secretions from patients with pollinosis, along with attenuation of clinical symptoms. The ability of levocetirizine to reduce RANTES and eotaxin levels may account, at least in part, for the clinical efficacy of the agent for allergic disorders, including allergic rhinitis.

Enhancement of clara cell 10-kD protein (CC10) production from nasal epithelial cells by fexofenadine hydrochloride.

BACKGROUND: Clara cell 10-kD protein (CC10) is well known to be an immuno-suppressive protein secreted from airway epithelial cells after inflammatory stimulation and is involved in the development of allergic disorders. Although histamine H1 receptor antagonists are used for the treatment of allergic disorders, the influence of the agents on CC10 production is not well understood. In the present study, we examined the influence of a histamine H1 receptor antagonist, fexofenadine hydrochloride (FEX) on CC10 production in vitro and in vivo. METHODS: Nasal epithelial cells (5 x 10(6) cells/ml) were stimulated with 20 ng/ml TNF-alpha in the presence of various concentrations of FEX for 24 hours. CC10 levels in culture supernatants were examined by ELISA. Patients with Japanese cedar pollinosis were treated orally with FEX twice a day at a single dose of 60 mg for two weeks during Japanese cedar pollen season (February 2011 to April 2011). CC10 levels in nasal secretions were also examined by ELISA. RESULTS: The addition of FEX into cell cultures caused increase in CC10 production induced by TNF-alpha stimulation, and the minimum concentration that caused significant increase was 200 ng/ml. Oral administration of FEX also increased CC10 levels in nasal secretions from pollinosis patients along with attenuation of clinical symptoms. CONCLUSION: The ability of FEX to enhance CC10 production may account, at least in part, for the clinical efficacy of the agent in allergic disorders, including allergic rhinitis.

Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro.

BACKGROUND: Thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) are accepted to be important molecules in the development and maintenance of allergic diseases. Although several types of histamine H(1) receptor antagonist (antihistamine) have been developed and used for the treatment of allergic diseases, the influence of antihistamines on TARC and MDC production is not well understood. OBJECTIVE: The present study was undertaken to examine the influence of antihistamines on TARC and MDC production from CD14+ cells after antigenic stimulation in vitro. METHODS: CD14+ cells prepared from patients with pollinosis to Japanese cedar pollen were stimulated with specific allergen extracted from Japanese cedar pollen (Cry j 1) in the presence of azelastine (AZE), ketotifen (KET), fexofenadine (FEX) and oxatomide (OXA) for 6 days. TARC and MDC levels in culture supernatants were examined by ELISA. We also examined the influence of FEX on TARC and MDC mRNA expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and transcription factor activation in CD14+ cells after Cry j 1 stimulation. RESULTS: FEX at 250 ng/ml, which is almost equal to therapeutic blood levels, caused a significant inhibition of TARC and MDC production.However, AZE, OXA and KET required higher concentrations than their therapeutic blood levels to suppress production of these factors. FEX at 250 ng/ml also suppressed NF-κB activation, phosphorylation of p38 MAPK and extracellular signal-regulated kinases 1 and 2 and expression of mRNA for TARC and MDC. CONCLUSIONS: These results suggest that antihistamines, especially FEX, suppress CC chemokine production from CD14+ cells through interference with antigen-mediated signaling and result in favorable modification of allergic disease states or conditions.

[Three cases of adenocarcinoma of the head and neck maintaining QOL by administration of docetaxel].

A primary head and neck adenocarcinoma is a comparatively rare disease, and surgical resection has been the first choice for its treatment. In the present study, we performed chemotherapy with weekly administration of docetaxel in 3 cases with unresectable or recurrent adenocarcinoma of the head and neck on an outpatient basis, resulting in long-term maintenance of the patients' QOL. Each case had submandibular gland carcinoma, parotid gland carcinoma, or parathyroid gland carcinoma. Their observation period was 42, 76, or 87 months, respectively. Docetaxel was administered for 18, 19, or 28 courses, respectively. No adverse events of grade 3 or higher were observed. The present results might suggest that it is possible to treat patients with adenocarcinoma in the head and neck without decreasing patients' QOL.

Typical carcinoid tumor arising in the nose and paranasal sinuses--case report.

Carcinoid tumors arise from neuroendocrine cells, many of which are present in the digestive tract and lungs. There have been few reports of carcinoid tumors occurring in the nose and paranasal sinus area, and they are very rare. We encountered a patient with a carcinoid tumor that arose in the nose and paranasal sinuses, and we report the case with a review of the literature. The patient was a 75-year-old woman who began to experience right-sided nasal obstruction, and when her nose began to bleed on the right-side she was examined in our department. A tumor lesion that easily bled and had filled the right nasal cavity was observed. CT revealed a mass lesion with a marked contrast enhancement in the right nasal cavity, ethmoid sinus, and sphenoid sinus, and MRI showed numerous flow voids in the interior that seemed to be tumor blood vessels. The tumor was excised through a lateral rhinotomy. The histopathological diagnosis was a carcinoid tumor. Tumor recurrence was subsequently detected in the vicinity of the opening of the sphenoid sinus, and because the tumor was tending to grow larger, the tumor was resected. The patient has been followed up in the outpatient clinic, recurrence-free.

Suppressive activity of epinastine hydrochloride on eosinophil activation in vitro.

The influence of a histamine H1 receptor antagonist, epinastine hydrochloride (EP), on eosinophil functions was examined in vitro and in vivo. The first set of experiments was undertaken to examine whether EP could suppress eosinophilia and IgE hyperproduction induced by Mesocestoides cortii infection in BALB/c mice. The number of peripheral blood eosinophils and levels of IgE were examined 21 days after infection. Oral administration of EP at a daily dose of 0.3 mg/kg, which is the recommended human therapeutic dose, for 21 days was not able to suppress either peripheral blood eosinophilia or IgE hyperproduction, which was observed in mice infected with M. cortii. The second part of the experiment was designed to examine the influence of EP on eosinophil activation induced by stem cell factor (SCF) stimulation in vitro. Eosinophils were obtained from M. cortii-infected mice and stimulated with SCF in the presence of different concentrations of EP for 24 h. The addition of EP into cell cultures suppressed eosinophil activation induced by SCF stimulation as assessed by measuring the contents of acronym for Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES), macrophage inflammatory protein-1beta (MIP-1beta) and leukotriene C4 (LTC4) levels in culture supernatants. The minimum concentration of EP which caused significant suppression of factor productions was 25 ng/ml, which is similar to the concentration in plasma after oral administration of the therapeutic dose in humans. These results may suggest that EP exerts inhibitory effects on eosinophil activation and results in favorable modification of the clinical status of allergic patients.

Suppressive activity of fexofenadine hydrochloride on nitric oxide production in-vitro and in-vivo.

The aim of this study was to examine the effect of fexofenadine hydrochloride (FEX), a histamine H1-receptor antagonist, on nitric oxide (NO) production in-vitro and in-vivo. Nasal fibroblasts (5 x 10(5) cells per mL) were stimulated with 25 ng mL(-1) tumour necrosis factor-alpha in the presence of various concentrations of FEX. NO levels in 24-h-culture supernatants were measured by the Griess method and levels of inducible nitric oxide synthase (iNOS) mRNA levels in 12-h-cultured cells were measured by ELISA. FEX at more than 0.5 microg mL(-1) suppressed NO production from fibroblasts by inhibiting expression of iNOS mRNA. We also examined whether FEX could suppress NO production induced by lipopolysaccharide (LPS) stimulation in-vivo. BALB/c mice were treated with 5.0 mg kg(-1) LPS i.p. after daily oral doses of FEX, 1.0 mg kg(-1), for 1-3 weeks. Plasma was obtained 6 h later and NO levels measured by the Griess method. Expression of iNOS mRNA in lung tissues was measured by ELISA 6 h after LPS injection. Oral administration of FEX for 2 and 3 weeks, but not 1 week, significantly suppressed NO levels in plasma through the inhibition of iNOS mRNA expression, which were enhanced by LPS stimulation. These results suggest that the attenuating effect of FEX on NO production may be of therapeutic benefit in allergic diseases.

[Odor stick identification test for Japanese patients with olfactory disturbances].

In recent years, a new stick-type odor identification test, the odor-stick identification test for Japanese (OSIT-J) has been developed in Japan. Thirteen odors familiar to Japanese people are used in this test. The OSIT-J is an olfactory discrimination test and is significantly correlated with the average recognition threshold of T & T olfactometry, which is the standard olfactory acuity test used in Japan. In this study, we evaluated the accuracy of the OSIT-J in patients with olfactory disturbances. We compared the OSIT-J and T & T olfactometry results and examined the sensitivity and specificity of the OSIT-J. Using the OSIT-J, olfactory disturbances were diagnosed in more than 70% based on the average recognition threshold determined by T & T olfactometry. OSIT-J is a simple test and is recommended for use in clinical practice for evaluating olfactory disturbances.