Evidence-Based Clinical Guidelines for Chronic Constipation 2023.

The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide.

Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.

The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and antidiarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogues, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.

Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study.

BACKGROUND: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods. METHODS: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19. RESULTS: Among 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081-2.441). CONCLUSION: These findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.

Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation.

Developmental defects of primitive choanae, an anatomical path to connect the embryonic nasal and oral cavity, result in disorders called choanal atresia (CA), which are associated with many congenital diseases and require immediate clinical intervention after birth. Previous studies revealed that reduced retinoid signaling underlies the etiology of CA. In the present study, by using multiple mouse models which conditionally deleted Rdh10 and Gata3 during embryogenesis, we showed that Gata3 expression is regulated by retinoid signaling during embryonic craniofacial development and plays crucial roles for development of the primitive choanae. Interestingly, Gata3 loss of function is known to cause hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, which exhibits CA as one of the phenotypes in humans. Our model partially phenocopies HDR syndrome with CA, and is thus a useful tool for investigating the molecular and cellular mechanisms of HDR syndrome. We further uncovered critical synergy of Gata3 and retinoid signaling during embryonic development, which will shed light on novel molecular and cellular etiology of congenital defects in primitive choanae formation.

Craniofacial and dental characteristics of three Japanese individuals with genetically diagnosed SATB2-associated syndrome.

Craniofacial defects are one of the most frequent phenotypes in syndromic diseases. More than 30% of syndromic diseases are associated with craniofacial defects, which are important for the precise diagnosis of systemic diseases. Special AT-rich sequence-binding protein 2 (SATB2)-associated syndrome (SAS) is a rare syndromic disease associated with a wide variety of phenotypes, including intellectual disability and craniofacial defects. Among them, dental anomalies are the most frequently observed phenotype and thus becomes an important diagnostic criterion for SAS. In this report, we demonstrate three Japanese cases of genetically diagnosed SAS with detailed craniofacial phenotypes. The cases showed multiple dental problems, which have been previously reported to be linked to SAS, including abnormal crown morphologies and pulp stones. One case showed a characteristic enamel pearl at the root furcation. These phenotypes add new insights for differentiating SAS from other disorders.

Morphologic variations in the craniofacial structures in Japanese adults and their relationship with sex differences.

INTRODUCTION: The morphology of the human face varies broadly, with genetic and environmental factors determining these variations. Examining variations in the 3-dimensional (3D) craniomandibular morphology and identifying related factors (eg, sex differences) are important in orthodontic clinics. This study observed shape variations in the 3D facial morphology of Japanese adults showing skeletal Class 1 malocclusion and examined the association of sexual dimorphism with shape variations. METHODS: Sixty cone-beam computed tomography images of Japanese adults (30 males and 30 females) with skeletal Class I malocclusion were employed. In each cone-beam computed tomography image, wire mesh fitting was conducted as previously described. A principal component (PC) analysis after Procrustes registration and the PC clustering method was conducted to observe the shape variations. A PC regression analysis was conducted to determine the sexual morphologic characteristics. RESULTS: Nine PCs depicting 62% of the morphology were determined. Four typical phenotypes were found, mainly related to mandibular protrusion (PC1) and the vertical divergence of the face (PC2). PCs related to sex determination were PC3 (robustness of the mandibular angle in males), PC5 (greater size and shape of the coronoid and mastoid processes in males), and PC7 (greater maxillary width in males), accounting for 16% of total variations. CONCLUSIONS: The major shape variations in skeletal Class 1 subjects were related to nonsexual dimorphic characteristics (ie, mandibular protrusion and facial divergence). Sexual dimorphic characteristics were evaluated in detail and accounted for 16% of total morphologic variations.

Immunological effects of sublingual immunotherapy with Japanese cedar pollen extract in patients with combined Japanese cedar and Japanese cypress pollinosis.

Sublingual immunotherapy (SLIT) with Japanese cedar (JCe) pollinosis was expected to be effective for Japanese cypress (JCy) pollinosis. However, only a half of JCy pollinosis patients clinically improved. Therefore, we examined the immunological effect of SLIT for JCy pollinosis. Peripheral blood mononuclear cells (PBMCs) from patients with JCe and JCy pollinosis who did and did not receive SLIT were incubated with Cry j 1, Cha o 1 and Cha o 3 antigens. Basophil activation test (BAT) were performed. Production of IL-5 and IL-17 induced by antigens was inhibited in the SLIT group. Cry j 1-specific production of IL-10 was increased, and serum Cry j 1-specific IgE and -IgG4 were elevated. However, Cha o 1- or Cha o 3-specific production of IL-10 and specific IgG4 was not increased. Antigens-specific BAT did not decrease after SLIT. New SLIT with JCe and JCy is needed for patients with combined JCe and JCy pollinosis.

Gut Environment and Dietary Habits in Healthy Japanese Adults and their Association with Bowel Movement.

INTRODUCTION: Constipation is a common symptom that impairs the quality of life (QOL). This study aimed to investigate the relationship between bowel movement and gut microbiota and dietary intake. METHODS: To investigate correlations among bowel movement, food intake, and gut environment, 60 healthy Japanese participants were recruited. Bowel movement was assessed using the Bristol stool form scale (BSFS) and constipation scoring system (CSS). Dietary habit was assessed with a self-administered questionnaire wherein the food intake frequency was classified into 8 categories for 72 food/food groups. Gut microbiota was analyzed using terminal restriction fragment length polymorphism analysis. RESULTS: The constipation rate was significantly higher in females than in males. The QOL was significantly impaired in the constipated group. The fecal count of Bacteroides was decreased and that of Clostridium cluster IV was increased in participants with constipation. The BSFS score was negatively associated with the fecal count of Clostridium cluster XI and positively associated with the fecal count of Clostridium cluster XVIII and consumption of green tea. The total CSS score was positively associated with the fecal Prevotella count and negatively associated with fecal acetate levels and consumption of vegetables. Discriminant analysis estimated that constipation could be predicted correctly in 83% (p < 0.001) of the participants based on fecal microbiota and fecal short-chain fatty acids. DISCUSSION/CONCLUSION: Bowel movement was strongly affected by gut environment and food intake in Japanese participants. Improvement in dietary habits could promote bowel movement through the improvement of the environment in the gut, resulting in ameliorated QOL issues in healthy adults.

The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative colitis.

The role of enterobacterial flora in the onset and progression of inflammatory bowel diseases is a topic of considerable interest. Here, we assessed the association among enterobacterial flora, dietary factors, and ulcerative colitis (UC) progression. Forty-six patients with UC who were diagnosed as being in remission were enrolled. We collected each patient's stool sample one or two days before diagnostic colonoscopy. After colonoscopy, we observed the patients for one year and then retrospectively divided them into two groups: remission (n = 39) and relapse (n = 7) groups, depending on whether the relapse occurred during the follow-up period, and analyzed the relationship among patient characteristics, dietary factors, enterobacterial flora, and UC relapse. Overall, there were no significant differences in bacterial community populations between the remission and relapse groups, except that the order Lactobacillales was detected at a significantly higher rate in the relapse than in the remission group (100% vs 71.4%, p<0.05). Vitamin C intake was significantly higher in the remission than in the relapse group (p<0.05). Although there were no obvious differences in enterobacterial flora between the remission and relapse groups, there was a relationship among enterobacterial flora, diet, and UC progression. Given that the enterobacterial flora was only analyzed at the initiation of the study, we conclude that in future analyses, enterobacterial flora should be sampled at numerous time points to examine its role in UC progression. Further long-term longitudinal studies examining enterobacterial flora, dietary factors, and UC progression are also required.

Evidence for the induction of Th2 inflammation by group 2 innate lymphoid cells in response to prostaglandin D2 and cysteinyl leukotrienes in allergic rhinitis.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play important roles in allergic inflammation. However, their roles in the pathophysiology of allergic rhinitis (AR) are poorly understood. OBJECTIVE: Prevalence of ILC2s in the inferior nasal turbinate (INT) tissues and the activating mechanisms of ILC2s were examined in patients with house dust mite (HDM)-induced AR. METHODS: Eighteen patients with HDM-induced AR and 13 control subjects were recruited. Fresh INT tissues and peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. Nasal lavage fluids (NLF) were collected at 10 minutes after the nasal provocation test (NPT) with HDM disc, and released mediators were measured by ELISA. Sorted ILC2s were cultured and stimulated with mediators associated with AR. RESULTS: The prevalence of ILC2s was significantly increased in nasal mucosa of patients with HDM-induced AR, and it was positively correlated with the number of infiltrating eosinophils. ILC2s in the INT tissues expressed a prostaglandin D2 (PGD2 ) receptor, chemoattractant receptor-homologous molecule-expressed TH2 cells (CRTH2) and a cysteinyl leukotriene (cysLTs) receptor, CysLT1. After NPT, the number of eosinophils and concentrations of PGD2 and cysLTs were significantly increased in the NLF from AR patients. PGD2 and cysLTs significantly induced IL-5 production from cultured PBMC-derived ILC2s dose-dependently. PGD2 -induced and cysLTs-induced productions of IL-5 and IL-13 from ILC2s were completely inhibited by ramatroban, a dual CRTH2 and thromboxane receptor antagonist, and montelukast, a CysLT1 antagonist, respectively. CONCLUSIONS: PGD2 -CRTH2 and cysLTs-CysLT1 axes may activate tissue-resident ILC2s to produce Th2 cytokines, IL-5 and IL-13, leading to the development of allergic inflammation in AR.

Characteristics and Predictive Factor of Helicobacter pylori-Associated Functional Dyspepsia in Japanese Patients.

BACKGROUND/AIM: Helicobacter pylori (HP) eradication therapy was first recommended as pharmacotherapy for functional dyspepsia (FD). However, the mechanism and effect of eradication on FD symptom improvement have not been fully investigated. This study aimed to investigate the pathology of patients with HP-associated FD, and predictive factors for HP-associated FD. METHODS: Ninety-seven patients with chronic gastritis caused by HP infection were divided into the group with FD symptoms and the group -without FD symptoms. Patient backgrounds, QOL, gastric mucosal atrophy severity, and serum pepsinogen (PG) value were compared between the 2 groups. Twelve months after eradication, those factors were evaluated between HP-associated FD and HP-non-associated FD, and predictive factors of HP-associated FD were analyzed. RESULTS: The FD-positive group existed in 45 (46.3%) out of 97 patients. Twelve months after eradication, there were 34 patients (75.6%) in the HP-associated FD. The mean PG I value in the HP-associated FD was significantly lower than that in the HP-non-associated FD, while the PG II values in the HP-associated FD tended to be lower than those in the HP-non-associated FD. QOL in the HP-associated FD significantly improved after HP eradication. On multivariate logistic regression analysis, it was found that PG II value was a significant predictive factor for FD symptom improvement in the HP-associated FD. CONCLUSION: HP eradication is an effective initial therapy for FD. PG II value is considered a predictive factor for FD symptom improvement through HP eradication.

[Internet survey of the actual situation of constipation in Japanese general population REACTION-J:Research for Actual Situation of Constipation in the Japanese].

Although chronic constipation is highly prevalent, its definition remains unclear. Therefore, the prevalence varies depending on reports, and the understanding of actual situations is unclear. Hence, we performed an internet survey on constipation among the Japanese general population to study the background factors and actual situations. Preliminary study on the awareness of constipation was conducted among 10000 people in which 9523 of them was asked if they had constipation at the time of the survey. In this population, 51.5% realized that they had constipation. Multivariate analysis showed the significant association of constipation to age, sex, and past histories or complications of diabetes, hemorrhoids, and cerebrovascular diseases. In a main research composed of 3000 general Japanese population, approximately 30.9% of the subjects reported the use of laxatives to treat constipation, and 43.8% of them were found to use irritant laxatives. Moreover, 67.5% of the subjects purchased laxatives at a pharmacy. The frequency of bowel movement less than 3 times per week was manifested in 36.3% of the subjects, and more than once per week in 21.4%. The percentage of hard (Bristol Stool Form Scale [BSFS] Type 1-2), normal (BSFS Type 3-5), and diarrhea stools (BSFS Type 6-7) was 33.1%, 60.0%, and 6.9%, respectively. The quality of life (QOL) of the subjects with hard and diarrhea stools evaluated by SF-8 was significantly lower than that of those with normal stools. Furthermore, the actual monthly cost for the therapeutic drugs used for treating constipation was less than 1000 yen in 75% of the subjects. Analysis of the IBS-QOL-J indicated that the ≥5000 yen payable group had the lowest satisfaction of defecation among the study groups. At present, many Japanese patients with constipation have not been receiving enough treatment for constipation. Therefore, appropriate medication by physicians as well as instruction to patients is required.

[Usefulness of Clinicobiological Data Obtained Prior to Cervical Lymph Node Biopsy].

INTRODUCTION: We commonly use data obtained prior to cervical lymph node biopsy for the diagnosis of malignant lymphoma. Based on such data, we can confirm whether a biopsy should be performed in some cases. Currently, the parameters used to indicate a presurgery examination prior to biopsy have been very few. So, we retrospectively analyzed cases of cervical lymph node biopsy. Moreover, we examined the usefulness of clinicobiological data obtained prior to cervical lymph node biopsy to evaluate various factors related to the diagnosis of malignant lymphoma. METHODS: This study included 77 patients for whom the initial diagnostic impression was malignant lymphoma before surgery. Of the 77 cases, 40 were diagnosed as having malignant lymphoma and 37 were diagnosed as having non-malignant lymphoma. We performed a case-controlled study to evaluate the differences in clinicobiological data between malignant and non-malignant lymphoma in terms of the following parameters: (1) age, (2) sex, (3) number of white blood cells, (4) white blood cell lymphocyte count, (5) percentage of white blood cell lymphocytes, (6) percentage of eosinophils (%), (7) percentage of monocytes (%), (8) atypical lymphocytes (%), (9) hemoglobin level, (10) lactate dehydrogenase level, (11) C-reactive protein level, (12) soluble interleukin-2 receptor (IL-2R) level, and (13) cytological findings. We used multivariate and univariate analyses to study the data statistically. RESULTS: The following 5 factors were found to be significant in a Wilcoxon t-test for malignant lymphoma: percentage of white blood cell lymphocytes, sIL-2R level, age, white blood cell lymphocyte count, and cytological findings; these factors were also significant when examined using a Pearson χ2 test. The other factors did not differ significantly between the malignant and non-malignant lymphomas. The percentage of white blood cell lymphocytes and the cytological findings were identified as significant independent factors for the diagnosis of malignant lymphoma in a multivariate analysis, whereas the other factors were not found to be significant. CONCLUSION: Based on the results of the univariate and multivariate analyses performed in the present study, the decline in the percentage of white blood cell lymphocytes and the cytological findings obtained prior to cervical lymph node biopsy are significant indicators of malignant lymphoma.

Carbohydrate-based amphiphilic diblock copolymers with pyridine for the sensitive detection of protein binding.

Glycopolymers are useful macromolecules for presenting carbohydrates in multivalent form. Here, amphiphilic block copolymers consisting of hydrophilic lactose and hydrophobic pyridine were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT). RAFT polymerization of 2-O-methacryloyloxyethyl-(ß-D-lactoseheptaacetate) (2-O-MALac) was performed using cumyl dithiobenzoate (CDB) as the chain transfer agent to give well-defined glycopolymers. The livingness of the process was further demonstrated by successfully chain-extending one of obtained glycopolymers with 4-pyridyl methyl methacrylate affording narrow dispersed diblocks. With the obtained block copolymers, a glycosurface was generated on the gold surface of quartz crystal microbalance (QCM) through self-assembled strategy by the use of gold affinitive pyridine functional group. Furthermore, the resulting glycosurface was used to detect the binding of lactose specific lectin, ricinus communis agglutinin (RCA120) without non-specific protein adsorption.

Characteristic craniofacial defects associated with a novel USP9X truncation mutation.

Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.

Factors Associated with Defecation Satisfaction among Japanese Adults with Chronic Constipation.

Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation.

Long-term follow-up of a patient diagnosed with Crouzon syndrome who underwent Le Fort I and III distraction osteogenesis using a rigid external distractor system.

OBJECTIVE: This case report describes the successful treatment of a patient with Crouzon syndrome with severe midfacial deficiency and malocclusion, including reverse overjet. MATERIALS AND METHODS: In Phase I treatment, maxillary lateral expansion and protraction were performed. In Phase II treatment, after lateral expansion of the maxilla and leveling of the maxillary and mandibular dentition, an orthognathic approach including simultaneous Le Fort I and III osteotomies with distraction osteogenesis (DO) was used to improve the midfacial deficiency. RESULTS: After DO, 12.0 mm of the medial maxillary buttress and 9.0 mm of maxillary (point A) advancement were achieved, which resulted in a favorable facial profile and stable occlusion. CONCLUSION: Even after 8 years of retention, the patient's profile and occlusion were preserved without any significant relapse.

Background factors involved in the epidemiology of functional constipation in the Japanese population: a cross-sectional study.

BACKGROUND: Functional constipation (FC), a functional bowel disorder with symptoms of constipation, has considerable impact on quality of life. As data regarding its prevalence and epidemiology are lacking, this study aimed to evaluate the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of these individuals by comparing people with and without FC. These parameters were also compared among individuals with strong and weak awareness of constipation. METHODS: An internet survey was conducted among 10,000 individuals aged 20-69 years from the general Japanese population; they were registered with an internet survey company. The following data were obtained: age, sex, educational history, occupation, residence, history of other diseases, lifestyle (including smoking/drinking habits using the Japanese Health Practice Index, medication use, symptoms of constipation according to the Rome III criteria, stool types according to the Bristol stool scale, and use of laxatives, including the place of purchase and cost per month or acceptable cost per month. The 8-item Short Form Health Survey Questionnaire was also used; FC was diagnosed based on Rome III criteria. All respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared. RESULTS: The data of 3000 respondents were evaluated; 262 (8.7%) had FC, which was common among older adults, women, and homemakers. FC was associated with changes in the frequency of bowel movement, sensation of incomplete or scanty evacuation, and the use of manual maneuvers; these are consequential clinical symptoms of FC. These individuals frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than those without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group. CONCLUSIONS: Appropriate and comprehensive management should be provided for FC, based on the understanding of its characteristic features and considering the symptoms and lifestyle.