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Background@#Transient receptor potential canonical (TRPC) channels are non-selective cationic channels with perme‑ ability to Ca2+ and Na+ . Despite their importance, there are currently few studies on TRPC in the periodontal ligament (PDL) and bone cells in the dental field. To provide biological information regarding TRPC in PDL cells and periodontal tissue, we evaluated TRPC channels expression in the osteoblast differentiation of PDL cells and periodontitis-induced tissue. Human PDL cells were cultured in osteogenic differentiation media for 28 days, and the expression of Runx2, osteocalcin (OCN), and TRPC1, 3, 4, and 6 was evaluated by real-time PCR. In ligature-induced periodontitis mice, the alveolar bone and osteoid areas, the osteoclast number, and the expression of Runx2, OCN, TRPC3, and TRPC6 was evaluated by H&E staining, TRAP staining, and immunohistochemistry, respectively. @*Results@#In the PDL cell differentiation group, TRPC6 expression peaked on day 7 and TRPC3 expression generally increased during differentiation. During the 28 days of periodontitis progression, alveolar bone loss and osteoclast numbers increased compared to the control group during the experimental period and the osteoid area increased from day 14. TRPC6 expression in the periodontitis group increased in the PDL area and in the osteoblasts compared to the control group, whereas TRPC3 expression increased only in the PDL area on days 7 and 28. @*Conclusions@#These results indicate changes of TRPC3 and TRPC6 expression in PDL cells that were differentiating into osteoblasts and in periodontitis-induced tissue, suggesting the need for research on the role of TRPC in osteo‑ blast differentiation or periodontitis progression.
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Background@#Using path analysis, we aimed to examine whether parenting self-efficacy and parenting styles would be significant associates with parenting behavior, and the parenting behavior would be significantly associated with the obesity status of children from socioeconomically vulnerable families. @*Methods@#A cross-sectional study was conducted with 61 parents and their children enrolled in public welfare systems in a community in Seoul, South Korea. Parenting behavior was defined as encouraging a child’s healthy eating habits and was measured using the Child Feeding Questionnaire. @*Results@#In the path model, higher levels of parenting self-efficacy and lower levels of authoritarian parenting were significantly associated with a higher level of parenting behavior, which was significantly associated with lower child body mass index z-scores. @*Conclusions@#Community health nurses need to provide intervention strategies for increasing parenting self-efficacy and decreasing authoritarian parenting styles to promote parenting behaviors and childhood obesity prevention among socioeconomically vulnerable families.
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Although multiple factors influence the risk of major adverse cardiovascular events (MACE), the effects of socioeconomic status on MACE in the presence and absence of renal dysfunction (RD) have not been comprehensively explored in Korea. Methods: We examined the effects of socioeconomic status on MACE in individuals with and without RD. The data of 44,473 Koreans from 2008 to 2017 were obtained from the Health Care Big Data Platform of the Ministry of Health and Welfare in Korea. Their socioeconomic status was assessed using a socioeconomic score (SES) based on marital status, education, household income, and occupation. The incidence of myocardial infarction (MI), stroke, and death was compared according to SES level (0–4). Multiple linear regression analysis was used to evaluate the hazard ratios and 95% confidence intervals for outcomes based on participant SES. Results: MI risk was only affected by education level. The participants’ income, education, and SES affected their stroke risk, whereas death was associated with all four socioeconomic factors. The incidence of stroke and death increased as SES worsened (from 0 to 4). SES was positively related to risk of stroke and death in participants without RD. SES did not affect MI, stroke, or death in participants with RD. Conclusion: A low socioeconomic status is associated with risk of stroke and death, especially in individuals without RD.
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Objective:To compare the detection success rates (DSRs) of different kinds of near-infrared spectrum non-invasive hemoglobin monitors in high-altitude environments.Methods:One hundred and forty-four healthy volunteers of either sex, aged 18-50 yr, were assigned to one of 3 groups using a random number table method: simulated high-altitude 3 500 meter group ( n=35), 4 000 meter group ( n=55) and 4 500 meter group ( n=54). Hemoglobin was detected by Radical-7, NW-9002SHM, A5 and TensorTip MTX type hemoglobin monitors in plain environment and simulated environment at different altitudes, and the DSRs were compared.Logistic regression analysis was conducted to identify the risk factors affecting the success rate of instrument detection, and the cut-off value was determined by ROC curve and the Youden index. Results:In the simulated high-altitude environment of 3500, 4000 and 4500 m, the DSR of TensorTip MTX was significantly higher than that of Radical-7, NW-9002SHM and A5 ( P<0.001), and there was no significant difference in the DSR among Radical-7, NW-9002SHM and A5 ( P>0.05). Low SpO 2 was the main factor affecting the DSRs of the Radical-7, NW-9002SHM and A5 type hemoglobin monitor in high-altitude environment ( P<0.001), and the cut-off value of SpO 2 in determining the success of detection was 88.5%, 87.5% and 89.5%, respectively.The DSR of TensorTip MTX was not affected by low SpO 2. Conclusions:The DSR of TensorTip MTX hemoglobin monitor is minimally affected by the high-altitude environment and can be preferred in the absence of oxygen supply; when Radical-7, NW-9002SHM or A5 hemoglobin monitor applied in high-altitude environments, oxygen saturation needs to be increased to ensure a high DSR.
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ObjectiveTo discuss the effect of forgetting curve based self-management on cognitive function， daily living ability and treatment efficacy of patients with mild cognitive impairment （MCI）. MethodsSimple random sampling method was adopted to enroll 162 MCI patients who met the diagnostic criteria of "Expert Consensus on the Prevention and Treatment of Cognitive Impairment in China" in Nanchong Physical and Mental Hospital and Gaoping Ledele Seniors-Oriented Apartment from April 2020 to June 2021. The selected individuals were classified into study group and control group according to random number table methods， each with 81 cases. Both groups received routine intervention， based on this， study group received the forgetting curve based self-management. The interventions lasted for 3 months in two groups， and patients were assessed using Montreal Cognitive Assessment Scale （MoCA） and Activity of Daily Living Scale （ADL） at the baseline and end of interventions. Then the clinical efficacy was compared between groups. ResultsAfter intervention， an increase was found in MoCA and ADL scores in both groups （tcontrol group=25.004， 12.503， tstudy group=48.211， 24.949， P<0.01）， and post-intervention MoCA and ADL scores in study group were higher than those in control group （t=28.527， 9.433， P<0.01）. The overall efficacy rate was 86.42% in control group， which was lower than 96.30% in study group， with statistical difference （χ²=5.004， P<0.05）. ConclusionForgetting curve based self-management may ameliorate the cognitive function and daily living ability in MCI patients， thus improving the treatment efficacy.
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Background/Aims@#The obesity paradox has been known in end-stage renal disease (ESRD). However, the effect of body mass index (BMI) or waist circumference (WC) prior to percutaneous coronary intervention (PCI) on the development of ESRD is not clear. @*Methods@#Using nationally representative data from the Korean National Health Insurance System, we enrolled 140,164 subjects without ESRD at enrolment who underwent PCI between 2010 and 2015, and were followed-up until 2017. Patients were stratified into five levels based on their baseline BMI and six levels based on their WC with 5-cm increments. BMI and WC were measured at least 2 years prior to PCI. The primary outcome was the development of ESRD. @*Results@#During a median follow-up of 5.4 years, 2,082 (1.49%) participants developed ESRD. The underweight group (hazard ratio [HR], 1.331; 95% confidence interval [CI], 0.955 to 1.856) and low WC (< 80/< 75) (HR, 1.589; 95% CI, 1.379 to 1.831) showed the highest ESRD risk and the BMI 25 to 30 group showed the lowest ESRD risk (HR, 0.604; 95% CI, 0542 to 0.673) in all participants after adjusting for all covariates. In the subgroup analysis for diabetes mellitus (DM) duration, WC < 85/80 cm (men/women) increased ESRD risk in only the DM group (DM < 5 years and DM ≥ 5 years) compared to the reference group (85–90/80–85 of WC), but not the normal or impaired fasting glucose group. @*Conclusions@#Low WC prior to PCI showed an increased ESRD risk in patients with DM undergoing PCI as compared to those without DM.
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End-stage renal disease (ESRD) patients on hemodialysis have poor nutritional status and associated problems such as inflammation and sarcopenia. Blood urea nitrogen (BUN) is an important measure of uremic toxins, and urea reduction is a marker of hemodialysis efficacy. However, a low protein diet for lower BUN could aggravate malnutrition in patients, and optimal pre-dialysis BUN is not defined. We investigated the association of pre-dialysis BUN with patients’ comorbidities and the relationship between pre-dialysis BUN and serum albumin as a nutrient marker. Among the 67 patients, the average pre- and post-dialysis BUN were 59.2 and 15.0 mg/dL, respectively, serum creatinine was 10.1 mg/dL, and the average serum albumin was 4.0 g/dL. Patients’ age was negatively correlated with serum creatinine (r=−0.277, p<0.05) and albumin (r=−0.453, p<0.001). Predialysis BUN showed a significant positive correlation with serum albumin (r=0.287, p<0.05) and creatinine (r=0.454, p<0.001). However, the predialysis BUN was not significantly related to diabetes, coronary artery disease, congestive heart failure, or cerebrovascular disease. Hemodialysis patients with high pre-dialysis BUN and high serum creatinine could be regarded as having good nutritional status. The significance of this study lies in the potential utility of pre-dialysis blood urea nitrogen as an indicator of the nutritional status of patients. Liberal protein intake might be recommended to adequately dialyzed patients.
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Objective@#This study analyzed the relationship between sociodemographics and health behaviors that affect depression and stress of the aged 65 or older living in Seoul in 2018. @*Methods@#The subjects were selected according to the purpose by receiving raw data from the Korea Centers for Disease Control and Prevention, and 5,753 respondents were analyzed. @*Results@#In depression, the demographic and sociological factors with differences were sex, marriage, single-person household,current basic living, economic activity and monthly income, and the health behaviors with significant differences were past smoking, diabetes and insufficient annual medical use. In the stress level, the demographic and sociological factors with differences were age, sex, current basic living, monthly income and education, and the health behaviors with significant differences were current/past smoking, diabetes and insufficient annual medical use. The factors affecting depression and stress were not completely consistent but similar, and both had low rates of expert counseling. @*Conclusion@#This study is meaningful in that it identified the factors affecting the depression and stress of the elderly especially in Seoul, the metropolitan city. If future research reveals additional factors, it will be helpful to suggest the direction of government policy and contribute to improving the quality of life of the elderly in the super-aged era.
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Microglia differ from macrophages with unique origin and role. In glioblastoma, microglia plays an important role in regulating tumor immune status, promoting tumor angiogenesis, destroying the blood-brain barrier, and reducing the sensitivity of treatment. Therefore, the combination of microglial therapy in the radiotherapy, chemotherapy and immunotherapy of glioblastoma has also become a clinically promising treatment.
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Objective@#To evaluate the predictive performance of anthropometric indices for metabolic syndrome (MetS) among Chinese adolescents with different nutritional status.@*Methods@#We recruited 9,513 adolescents aged 10-18 years from seven provinces in China during September 2014. Anthropometric indices and blood pressure were measured at recruitment, and blood samples were collected for determining fasting plasma glucose and lipid profile. Receiver operating characteristic (ROC) analyses were used to assess the predictive performance of anthropometric indices, including body mass index (BMI) percentile, waist circumference percentile, waist-height ratio, and waist-hip ratio.@*Results@#Overall, the four anthropometric indices showed good accuracy for predicting MetS with areas under ROC curves (AUCs) ranging from 0.86 to 0.94; similar AUCs ranging from 0.73 to 0.99 were observed for participants with normal weight. The performance of all four indices was poor in overweight and obese participants, with AUCs ranging from 0.66 to 0.77 and from 0.60 to 0.67, respectively. Waist circumference showed relatively better performance in all the subgroup analyses.@*Conclusions@#We suggest using anthropometric indices with the cutoff values presented here for predicting MetS in the overall and normal-weight adolescent population, but not in the overweight and obese adolescent population where more specific screening tests are required.
Subject(s)
Adolescent , Child , Female , Humans , Male , Asian People , Body Weights and Measures , China , Cross-Sectional Studies , Metabolic Syndrome/diagnosis , Nutritional Status , Randomized Controlled Trials as TopicABSTRACT
Background@#The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. @*Methods@#This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. @*Results@#Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53%) and infection (44%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. @*Conclusions@#Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.
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Purpose@#The purpose of this study was to investigate the actual utilization of clinical practice guidelines developed by Hospital Nurses Association. @*Methods@#The subjects were 70 nurses who were in charge of guideline distributions in 70 advanced general hospital and general hospitals with 500 beds or more nationwide.Data were collected between June and August, 2020 by mail (return rate: 88.6%). Data were analyzed using descriptive statistics, t-test, and ANOVA with SPSS/WIN 24.0. @*Results@#Among the clinical practice guidelines developed by Hospital Nurses Association, 72.9~90.1% were placed with book and electronic file in nursing department and 24.3~35.8% were placed with book and electronic file in each nursing unit at hospital. The average number of utilized clinical practice guidelines were 3.96±3.88, and average score of guideline utilization was score 2.85±0.79 which means ‘use sometimes’. @*Conclusion@#To improve the distribution and utilization of the clinical practice guidelines, it is necessary to enhance the recognition of values of evidence based nursing practice targeting head of nursing department and to stimulate the distribution and utilization of the clinical practice guidelines using diverse education programs for staff nurses.
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Purpose@#This study aimed to comprehensively explore the associations of socioeconomic status, parenting style, and grit with children's health behaviors. @*Methods@#This was a cross-sectional study of 1,040 parents and their children using data from the 2018 Korean Children's Panel Survey. Socioeconomic status was measured in terms of household income and subjective socioeconomic status. Parenting style and grit and were measured using 62 and 8 items, respectively. Health behaviors were measured by assessing healthy eating habits, physical activity, and sedentary behavior. @*Results@#Higher household income (β=.07, p=.018) and high maternal levels of an authoritative parenting style (β=.20, p2 hours on weekdays (OR=0.43, 95% CI=0.27-0.69). @*Conclusion@#We suggest that when planning interventions to improve children's health behavior, it is essential to adopt a multifaceted approach that avoids practicing a maternal permissive parenting style, promotes an authoritative parenting style, and incorporates strategies to increase children's grit.
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Objective:To investigate the incidence and clinical characteristics of Kawasaki disease complicated with arthritis, and explore the relationship with coronary artery disease.Methods:Patients diagnosed with Kawasaki disease at Xiamen Children′s Hospital from January 2015 to June 2020 were included in this study.They were divided into the arthritis group( n=53) and the non-arthritis group( n=401), depending on whether complicated with arthritis.Demographic, clinical symptoms, and laboratory results were retrospectively analyzed. Results:A total of 454 children were included in this study with 53 cases acomplicated with arthritis.There were 32 male cases and 21 female cases.The average age of arthritis group was(5.89±1.35) y, which was older than non-arthritis group[(4.28±1.25) y, P=0.026]. Among the 53 cases of arthritis group, 36 cases (67.92%)of small jiont arthritis, 14 cases(26.41%)of coxitis, ten cases(18.87%)of carpitis, eight cases(15.09%)of gonitis, four cases(7.55%)of anconitis, and three cases(5.66%) of ankle arthritis were involved.There was a statistic difference in the prevalence of intravenous immunogloblin(IVIG)resistant between arthritis group and non-arthritis group(14 cases, 26.14% vs.43 cases, 10.72%, P=0.002). The inflammatory markers(CRP, TNF-α, IL-6) of the arthritis group were significantly higher than those in the non-arthritis group, and the differences were statistically significant( P<0.05, respectively). The incidence of coronary artery disease in the arthritis group(60.38%, 32/53) was higher than that in the non-arthritis group(52.37%, 210/401), but the difference was not statistically significant( P>0.05). Conclusion:Kawasaki disease with arthritis in children is self-limited, with no sequelae.Patients in the arthritis group have a higher rate of IVIG resistance and higher levels of inflammatory markers, but no significant difference in the incidence of coronary artery disease compared with those without arthritis.
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Purpose@#The study was conducted to investigate the correlation between perception of patient safety risk factors, patient safety competency, and safety nursing activities of nurses in hemodialysis units and identify factors affecting patient safety activities. @*Methods@#The participants were 146 nurses from 16 hemodialysis units located in Gyeongsangnam-do. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficient, and multiple regression analysis using the SPSS, version 24.0. @*Results@#The mean safety nursing activity score was 3.47±0.38. safety nursing activities of the participants were significantly correlated with patient safety competency. The characteristics showing significant differences in safety nursing activities were educational level, hospital type, hospital work experience, number of hemodialysis treatment per day, number of hemodialysis treatment per nurse, educational experience of patient safety, presence of a patient safety incident report registration system, and direct registration of patient safety incident report. The multiple regression analysis revealed that the factors influencing safety nursing activities were patient safety incident report, patient safety competency, and number of daily hemodialysis treatment (<5~7 times/day) per nurse (R2 =.34). @*Conclusion@#The results of this study suggest that the safety nursing activities of hemodialysis unit nurses should be intensified. In addition, the registration system of patient safety incident report and nurses’ competency on patient safety should be improved, and the number of hemodialysis per nurse should be fewer than 7 times per day.
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Purpose@#To determine effects of family conflict mitigation documentary programs on conflicts, autonomic nerve activation (ANA), and happiness of elderly in long-term care hospitals. @*Methods@#This study used a non-equivalent control group with a pretest-posttest design. It was conducted on 39 elderly patients (19 in the experimental group and 20 in the control group) in long-term care hospitals. The experimental group (n = 19) received family conflict mitigation documentary programs. The family conflict mitigation documentary programs consisted of four sessions (40-50 minutes per session). These programs were implemented in small groups, with each group having five elderly. Data were analyzed by sing the conflict checklist, the Oxford Happiness Questionnaire, Chi-square test with Fisher’s exact test, independent t-test, paired t-test, and repeated measure ANOVA using the SPSS/WIN 21.0 program. @*Results@#The participants in the experimental group showed significantly decreased scores of conflict (t = -2.31, p = .028) and the value of sympathetic nervous system activity (t = 8.36, p = .007) compared with those of the control group. The participants in the experimental group showed significantly increased the value of parasympathetic nervous system activity (t = -2.91, p = .008) and scores of happiness (t = 5.46, p < .001). @*Conclusion@#The family conflict mitigation documentary programs on conflicts, ANA, and happiness of the elderly in long-term care hospitals are effective intervention programs for mitigating conflicts between elderlies and their families and for improving happiness of the elderly in long-term care hospitals.
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Purpose@#The goal of this study was to see how different aerobic exercise intensities affected AMP-activated protein kinase (AMPK), reactive oxygen, and antioxidant enzymes in young mice during an 8-week period. @*Methods@#Forty male C57BL/6 mice, aged seven weeks, were randomly assigned to one of four groups: control (n = 10), low-intensity exercise (n = 10), moderate-intensity exercise (n = 10), and high-intensity exercise (n = 10). For eight weeks, aerobic activity was performed once a day for 35–40 minutes, five days a week. The data were analyzed using descriptive statistics, analysis of variance (ANOVA), chi-squared tests, and the Tukey test in the SPSS/WIN 25.0 program. @*Results@#Weight (p = .001) was substantially different between the moderate-intensity exercise group and the control group in AMPK (p < .001). In addition, there were no significant differences between the moderate-intensity exercise group and the control group in reactive oxygen malondialdehyde (MDA) levels (p = .136) and antioxidant enzyme superoxide dismutase (SOD) levels (p = .521). @*Conclusion@#These findings suggest that moderate-intensity aerobic exercise increased AMPK activation and helped young mice shed weight.
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Under physiological conditions, calcium (Ca2+ ) regulates essential functions of polarized secretory cells by the stimulation of specific Ca2+ signaling mechanisms, such as increases in intracellular Ca2+ concentration ([Ca2+]i ) via the store-operated Ca2+ entry (SOCE) and the receptor-operated Ca2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP3) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca2+ signaling and regulatory channels to mediate SOCE and ROCE in pancreatic acinar cells. Deletion of Homer2 (Homer2–/– ) markedly increased the expression of TRPC3, TRPC6, and Orai1 in pancreatic acinar cells, whereas these expressions showed no difference in whole brains of wild-type and Homer2–/– mice. Furthermore, the response of Ca2+ entry by carbachol also showed significant changes to the patterns regulated by specific blockers of SOCE and ROCE in pancreatic acinar cells of Homer2–/– mice. Thus, these results suggest that Homer2 plays a critical role in the regulatory action of the [Ca2+]i via SOCE and ROCE in mouse pancreatic acinar cells.
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Purpose@#The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment. @*Methods@#We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: 0.7 mg/kg/day (group C; n=28). @*Results@#The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively). @*Conclusion@#The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.
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Purpose@#The study was conducted to investigate the correlation between perception of patient safety risk factors, patient safety competency, and safety nursing activities of nurses in hemodialysis units and identify factors affecting patient safety activities. @*Methods@#The participants were 146 nurses from 16 hemodialysis units located in Gyeongsangnam-do. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficient, and multiple regression analysis using the SPSS, version 24.0. @*Results@#The mean safety nursing activity score was 3.47±0.38. safety nursing activities of the participants were significantly correlated with patient safety competency. The characteristics showing significant differences in safety nursing activities were educational level, hospital type, hospital work experience, number of hemodialysis treatment per day, number of hemodialysis treatment per nurse, educational experience of patient safety, presence of a patient safety incident report registration system, and direct registration of patient safety incident report. The multiple regression analysis revealed that the factors influencing safety nursing activities were patient safety incident report, patient safety competency, and number of daily hemodialysis treatment (<5~7 times/day) per nurse (R2 =.34). @*Conclusion@#The results of this study suggest that the safety nursing activities of hemodialysis unit nurses should be intensified. In addition, the registration system of patient safety incident report and nurses’ competency on patient safety should be improved, and the number of hemodialysis per nurse should be fewer than 7 times per day.