ABSTRACT
AIM: The aim of this study was to explore the effectiveness of an oral hygiene program combined with home-phone health promoting counseling for rural adults with metabolic syndrome. BACKGROUND: Metabolic syndrome is an important risk factor for cardiometabolic diseases. Evidence indicates that the poor oral hygiene and unhealthy lifestyles are closely related to metabolic syndrome. METHODS: A prospective quasi-experimental design involved a total of 136 community adults, with metabolic syndrome living in two rural townships, were clustered and conveniently assigned to intervention and control group between June 2017 and December 2018. The primary outcome was the change in cardiometabolic biomarkers. The secondary outcome comprised changes in the health-promoting behaviors. The intervention effect was assessed using a generalized estimating equation model. RESULTS: There were 80 and 56 participants in the intervention and control group, respectively. The mean age was 56â¯years and ranged from 33 to 70â¯years. The intervention group exhibited a greater improvement in body mass index (Pâ¯<â¯0.01), waist circumference (Pâ¯<â¯0.05), body fat percentage (Pâ¯<â¯0.05), triglyceride level (Pâ¯<â¯0.05), use of dental floss (Pâ¯<â¯0.05), regular tooth scaling (Pâ¯<â¯0.05), physical activity (Pâ¯<â¯0.001), and total score of health-promoting behaviors (Pâ¯<â¯0.001) than the control group. CONCLUSION: This study supports the use of an oral hygiene program combined with home-phone counseling, which offers more advantages than its counterpart. Considering the global epidemic of cardiometabolic diseases, this is a community health nursing model worth to replicate and evaluate. Further study should consider innovative strategies to improve the awareness and adoption of a healthy lifestyle in residents with cardiometabolic risks.
Subject(s)
Cardiovascular Diseases , Metabolic Syndrome , Adult , Aged , Cardiovascular Diseases/prevention & control , Counseling , Humans , Life Style , Middle Aged , Oral Hygiene , Prospective Studies , Research Design , Risk FactorsABSTRACT
Over the past two decades, studies have widely examined the effectiveness of pay-for-performance (P4P) programs by conducting biochemical tests and assessing complications; however, the reported effectiveness of such programs among participants selected through purposeful sampling is controversial. Therefore, the objective of the current study was to analyze the effectiveness of a P4P program on patients' prognoses, including hospitalization for chronic diabetic complications, and all-cause mortality during specific follow-up years by using a nationwide population-based database in Taiwan. Based on 125,315 newly diagnosed type 2 diabetes patient cohort during 2002-2006, two control sets were designed by propensity-score-matching strategy according to participation of P4P program and followed up to 2012. The results indicated that full participants demonstrated the lowest risks of developing complications and all-cause mortality compared with nonparticipants. These findings confirm the long-term effect of P4P programs on full participants and reveal that this effect is not due to confounding variables. The results indicate the importance of performance management and adherence to interventions for patients with chronic diseases in a long-term observation. Comprehensive and continuous care is suggested to improve patient prognosis and quality of care.
Subject(s)
Chronic Disease , Diabetes Mellitus, Type 2/therapy , National Health Programs/organization & administration , Reimbursement, Incentive/standards , Diabetes Mellitus, Type 2/mortality , Female , Humans , Longitudinal Studies , Male , Middle Aged , Propensity Score , TaiwanABSTRACT
OBJECTIVES: The incidence of non-alcoholic fatty liver disease (NAFLD) is significant in hepatitis C virus (HCV) carriers due to multiple mechanisms, and this worsens the progression of chronic liver diseases, such as cirrhosis and hepatocellular carcinoma, and death. The purpose of this study was to examine whether the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio correlates with the status of hepatosteatosis. DESIGN: A cross-sectional observational study. SETTING: Community-based annual examination in northern Taiwan. PARTICIPANTS: A total of 1354 participants (age 20â years or over) were enrolled after excluding participants with HCV seronegative, laboratory or questionnaires loss, moderate alcohol consumption, liver cirrhosis, tumours and postlobectomy. OUTCOME MEASURES: Fatty liver was diagnosed according to echogenic findings. NAFLD included grades 1-3 fatty liver and high-degree NAFLD defined grades 2-3 fatty liver. RESULTS: 580 males and 774 females with a mean age of 47.2 (SD=16.1) years were cross-sectionally studied. The participants with NAFLD have significantly higher levels of ALT/AST ratio, fasting glucose, triglyceride and systolic/diastolic blood pressure than non-NAFLD participants. The association between NAFLD and ALT/AST was significant even when adjusting for the metabolic syndrome (aOR 1.90; 95% CI 1.37 to 2.65; p<0.001). In patients with a high degree of NAFLD, the ALT/AST ratio was still a significant predictor for hepatosteatosis (aOR 2.44; 95% CI 1.58 to 3.77; p<0.001). CONCLUSIONS: The ALT/AST ratio could be a strong risk of hepatosteatosis in patients with chronic HCV infection.
Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Hepacivirus , Hepatitis C, Chronic/blood , Liver/pathology , Non-alcoholic Fatty Liver Disease/blood , Adult , Cross-Sectional Studies , Disease Progression , Female , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Humans , Liver/enzymology , Male , Metabolic Syndrome/blood , Metabolic Syndrome/complications , Middle Aged , Non-alcoholic Fatty Liver Disease/etiology , Risk Factors , Taiwan , Triglycerides/bloodABSTRACT
The literature has demonstrated that the continuity of diabetes care can lower medical service utilization and expenses. However, few studies have examined the effects of patients' medical care-seeking behaviors in the early stage after the diagnosis of diabetes on their long-term prognoses. This study aimed to examine the association of medical care-seeking behavior in the first year following diabetes diagnosis on the occurrence of diabetes-related complications among patients in Taiwan. This is a retrospective data collection with follow-up analysis and a nationwide population-based dataset in Taiwan. A total of 89,428 newly diagnosed type 2 diabetes mellitus patients during the period from 2000 to 2006 were followed up until 2010. The patients' medical care-seeking behaviors were classified as follows: high consistency to a physician, high consistency to a medical setting, medium consistency to providers, and low consistency to providers. The occurrence of diabetes-related complications and all-cause mortality were the primary outcomes of this study. Chi-square tests, ANOVAs, and Cox proportional hazard models were applied to examine the relationships between the predictors and medical outcomes. Compared to the patients with high medical care-seeking consistency to a physician, the multivariate-adjusted hazard ratios of diabetes-related complications occurrence among patients in the high consistency to a medical setting, medium consistency, and low consistency categories were 1.112 (95% CI 1.089-1.136, P < 0.001), 1.226 (95% CI 1.205-1.248, P < 0.001), and 1.536 (95% CI 1.504-1.567, P < 0.001) in outpatient visits and 1.032 (95% CI 0.992-1.074, P = 0.121), 1.056 (95% CI 1.022-1.092, P = 0.001), and 1.208 (95% CI 1.164-1.254, P < 0.001) in complication-incurred hospitalizations, respectively. The monotonic trend was sustained across different strata of age, gender, and disease complexity. The findings of this study suggest that the incentives of continuity of care and physician-patient relationship management should be reinforced during the early stage of diabetes care in future medical care systems.
Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Patient Acceptance of Health Care/statistics & numerical data , Patient-Centered Care/statistics & numerical data , Adult , Aged , Aged, 80 and over , Continuity of Patient Care , Female , Health Behavior , Humans , Male , Medicine , Middle Aged , Retrospective Studies , TaiwanABSTRACT
BACKGROUND: Tuberculosis is one of the major infectious diseases in Taiwan. It has an especially high prevalence in diabetes patients, in whom it is usually asymptomatic and are more likely to result in drug-resistant tuberculosis. The aim of the study was to aggressively screen high risk diabetic elderly, identify the prevalence of tuberculosis and its determinants. METHODS: Type 2 diabetes patients aged over 65 years were enrolled. They received chest X-rays, blood tests and the questionnaires to assess their medical history and symptoms. Suspicious cases were referred to the pulmonary or infectious disease outpatient clinics. Pulmonary tuberculosis was confirmed by sputum culture. Variables between groups were analyzed by Student t test, Chi-square test or Fisher's exact test. Risk factors were assessed using univariate logistic regression and multiple logistic regression. RESULTS: A total of 3,087 patients participated this screening program and 7 patients screened positive for pulmonary tuberculosis. Another 5 patients were being under treatment when participating screening program. The prevalence rate was 3.89 per thousand people. The patients with male gender, smoking, liver cirrhosis or subjective body weight loss were associated with an increased risk of tuberculosis significantly. Subjective body weight loss (OR: 6.635 [95% CI: 2.096-21.007]), liver cirrhosis (OR: 10.307 [95% CI: 2.108-50.395]) and history of smoking (OR: 3.981 [95% CI: 1.246-12.718]) are independent risk factors. Among all 73 patients with active tuberculosis or tuberculosis history, they tended to be male, lower body mass index (BMI), more smoking history, more alcohol consumption, more family history of tuberculosis, higher low density lipoprotein (LDL), and less hypertension. However, there was no significant difference in the glycated hemoglobin (HbA1c) levels between the tuberculosis group and non-tuberculosis group. CONCLUSIONS: Active screening program is helpful in detecting pulmonary tuberculosis in elderly diabetes patients. Subjective body weight loss, smoking and liver cirrhosis are independent risk factors.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Mass Screening , Tuberculosis, Pulmonary/diagnosis , Aged , Cross-Sectional Studies , Female , Hospitals, Community , Humans , Male , Prevalence , Risk Assessment , Risk Factors , Taiwan/epidemiology , Tuberculosis, Pulmonary/epidemiologyABSTRACT
BACKGROUND: Hepatitis C virus (HCV) infection is a serious disease worldwide and it leads to several serious hepatic sequels. Some studies find possible correlation between HCV and ischemic heart disease in retrospective observations. Based on lacked community-based evidence, the study aims to assess correlation between ischemic heart disease and chronic HCV infection via electrocardiogram (ECG) because its abnormalities is strongly associating with cardiovascular disease mortality. METHODS: The population was from one community health examination in December 2010 in a southern village of Taiwan. A total of 9856 participants were evaluated and finally 5015 eligible residents with age older than 40 years were included. The baseline characteristics and laboratory data in nonischemic ECG and ischemic ECG groups were compared, and multivariate-adjusted analysis was used to evaluate the risks to ischemic ECG. RESULTS: The higher prevalence of hypertension, metabolic syndrome and even HCV infection (25.3% versus 11.6%; P < 0.001) in ischemic ECG group than those in nonischemic ECG group. In the multivariate adjusted analysis, HCV infection would lead to a 1.759-fold risk to ischemic ECG when compared with non-HCV subjects. CONCLUSIONS: HCV was strongly associated with ischemic ECG findings in this community study, and it could be a nonconventional risk factor for coronary artery disease.
Subject(s)
Electrocardiography , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Myocardial Ischemia/diagnosis , Myocardial Ischemia/epidemiology , Adult , Aged , Electrocardiography/methods , Female , Hepatitis C/physiopathology , Humans , Male , Middle Aged , Myocardial Ischemia/physiopathology , Population Surveillance/methods , Retrospective Studies , Risk Factors , Taiwan/epidemiologyABSTRACT
AIMS AND OBJECTIVES: To explore the factors associated with the numbers of remaining teeth among type 2 diabetes community residents. BACKGROUND: Promoting oral health is an important nursing role for patients with diabetes, especially in disadvantaged areas. However, limited research has been carried out on the relationship between numbers of remaining teeth, diabetes-related biomarkers and personal oral hygiene among diabetic rural residents. DESIGN: A cross-sectional, descriptive design with a simple random sample was used. METHODS: This study was part of a longitudinal cohort study of health promotion for preventing diabetic foot among rural community diabetic residents. It was carried out in 18 western coastal and inland districts of Chiayi County in central Taiwan. In total, 703 participants were enrolled in this study. RESULTS: The findings indicated that a high percentage of the participants (26%) had no remaining natural teeth. Nearly three quarters (74%) had fewer than 20 natural teeth. After controlling for the potential confounding factors, multivariate analysis demonstrated that the factors determining numbers of remaining teeth were age (p < 0.001), education (p < 0.001), using dental floss (p = 0.003), ankle brachial pressure index (p = 0.028), waist circumference (p = 0.024) and HbA1C (p = 0.033). CONCLUSIONS: Except for some unmodifiable factors, the factors most significantly associated with numbers of remaining teeth were less tooth-brushing with dental floss, abnormal ankle brachial pressure and poor glycemic control. RELEVANCE TO CLINICAL PRACTICE: This study highlights the importance of nursing intervention in oral hygiene for patients with type 2 diabetes. It is necessary to initiate oral health promotion activities when diabetes is first diagnosed, especially for older diabetic residents of rural or coastal areas who are poorly educated.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Jaw, Edentulous, Partially , Tooth , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Oral cancer is the 2nd most common cause of death due to cancer in the south-western coastal region of Taiwan; the standardized mortality of oral cancer is higher than elsewhere in the world. According to the evidence, alcohol, betel-nut and cigarette (ABC) consumption cause oral, nasopharyngeal and related cancers. This study describes the relationships between ABC consumers and health promoting behaviors among community adults living around an area with a high prevalence of oral cancer. METHODS: A population-based, cross-sectional study design was conducted in oral cancer epidemic areas in south-western coastal Taiwan in 2010, 6,203 community residents over 20 years of age participated. Demographic data, ABC habits, and health-promoting behaviors were explored. A logistic regression analyses were used to identify factors associated with ABC consumers. RESULTS: A high percentage of participants consumed alcohol, betel-nut and cigarettes. Betel-nut and cigarette consumers took low levels of exercise, adopted a poor diet, and had poor oral hygiene. After adjusting for potential confounders, the logistic regression model indicated that middle aged males of poor education and low economic status, who did not exercise regularly and had poor oral hygiene, were more likely to chew betel quid and smoke cigarettes. CONCLUSIONS: It has identified that BC consumers are negatively associated with health promoting behaviors. Further research is required to understand the reasons why the subjects consume ABC, and explore ways to prevent initiation and enhance cessation of ABC habits in this population.
Subject(s)
Alcohol Drinking/epidemiology , Areca , Health Promotion , Mouth Neoplasms/epidemiology , Smoking/epidemiology , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Risk Factors , Taiwan/epidemiology , Young AdultABSTRACT
BACKGROUND: Peripheral arterial disease (PAD) is one of the major manifestations of systemic atherosclerosis and plays an important role in low-extremity amputation in type 2 diabetic patients. The aim of this study was to explore the prevalence and risk factors for asymptomatic PAD in type 2 diabetic community residents. METHODS: This cross-sectional study enrolled 552 type 2 diabetic adults (232 men and 320 women) without subjective symptoms of intermittent claudication. We defined the PAD group as an ankle-brachial index (ABI) ≤ 0.90, and the normal group as an ABI 0.91-1.30. Their clinical characteristics, Michigan Neuropathy Screening Instrument (MNSI) scores and blood pressure were compared. RESULTS: We discovered that 51 patients have asymptomatic PAD. Univariate logistic regression analysis revealed that age, history of stroke, longer duration of diabetes (> 10 years), unemployment or retirement, pulse pressure, systolic blood pressure, and high MNSI score (> 2) were risk factors for PAD. By multivariate logistic regression analysis, pulse pressure, high MNSI score, age, and history of stroke were independent risk factors with odds ratios (95% confidence intervals, CI) of 1.032 (1.012-1.053), 2.359 (1.274-4.370), 1.050 (1.010-1.091), and 5.152 (1.985-13.368), respectively. Furthermore, the prevalence of PAD increased significantly with increment in the pulse pressure and MNSI. CONCLUSIONS: In summary, the overall prevalence of asymptomatic PAD in the type 2 diabetic adults was 9.2%. Age, history of stroke, pulse pressure and MNSI score may provide important clinical information. Primary care physicians should be aware of asymptomatic patients with high pulse pressure and MNSI scores.
Subject(s)
Ankle Brachial Index , Blood Pressure/physiology , Diabetes Mellitus, Type 2/therapy , Peripheral Arterial Disease/therapy , Aged , Ankle Brachial Index/instrumentation , Ankle Brachial Index/methods , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Female , Humans , Male , Middle Aged , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/diagnosis , Risk Assessment , TaiwanABSTRACT
AIMS: To evaluate the self-perception of diabetes control associated with physical indicators and with practicing exercise and a healthy diet, among rural residents. BACKGROUND: It remains unclear whether a subject's self-perception of diabetes control increases its deleterious effects. DESIGN: Cross-sectional, correlational. METHODS: We recruited 715 participants from 18 primary healthcare centres in the rural regions of Chiayi County, Taiwan. Data were collected between 1 January 2009-30 June 2010. Logistic regression was conducted to identify the determinant factors associated with perceptions of diabetes control. RESULTS: A high percentage of participants overestimated their fasting blood glucose and HbA1 C status. Total cholesterol, triglyceride, low density lipoprotein cholesterol, blood pressure, and waist circumference exceeded the medical standard in the 'feel good' group, and many did not adopt a healthy diet and undertake physical activity. The final logistic regression model demonstrated that residents with diabetes who exercised frequently had normal fasting glucose, and normal HbA1 C tended to perceive 'feel good' control. CONCLUSION: Misperception and unawareness of diabetes control were prevalent among rural residents. Addressing misperceptions among rural residents with diabetes and increasing their knowledge of professional advice could be important steps in improving diabetes control in an elder population.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Rural Population , Adult , Blood Glucose/analysis , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Female , Glycated Hemoglobin/metabolism , Humans , Lipids/blood , Male , Middle Aged , TaiwanABSTRACT
OBJECTIVE: To assess the efficacy, safety, and tolerability of a combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS: A prospective, open-label, multi-center, hospital-based cohort study was conducted to evaluate the efficacy, safety, and tolerability of a single tablet combination of ezetimibe/simvastatin for the treatment of hypercholesterolemia. Taiwanese adults without low-density lipoprotein cholesterol (LDL-C) goal achievement, based on the National Cholesterol Education Program Adult Treatment Panel III guidelines, were treated with ezetimibe/simvastatin once daily for 6 weeks. The primary endpoint was the percentage of patients achieving LDL-C treatment goals after 6 weeks of treatment. Secondary endpoints included percentage change from baseline of LDL-C, total cholesterol, high-density lipoprotein cholesterol, and triglyceride. Safety and tolerability were assessed via clinical and laboratory examinations. The clinicaltrial.gov identifier of this study was NCT00654628. RESULTS: In total, 173 patients with a mean age of 57.9 ± 10.4 years were included. Of these, 57.8% were female and the average body mass index was 25.5 ± 3.4 kg/m(2). After 6 weeks of treatment, the great majority of the patients had reached their treatment goals (90.4% for LDL-C; 87% for TC; and 59% for TG). LDL-C levels were significantly reduced from 156.8 ± 30.8 mg/dL at baseline to 75.9 ± 25.4 mg/dL (51.4%, P < 0.0001) after only 6 weeks of therapy. Forty-nine adverse events (AEs), including one non-drug related serious AE, were reported. For non-serious AEs, the most common reported AEs during the entire study period were myalgia and upper respiratory infection (both n = 7). Nine patients dropped out of the study, reportedly due to AEs. CONCLUSIONS: A single tablet combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia provided high LDL-C goal attainment rates and resulted in significant reductions in LDL-C.
Subject(s)
Anticholesteremic Agents/administration & dosage , Azetidines/administration & dosage , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hypercholesterolemia , Simvastatin/administration & dosage , Triglycerides/blood , Adult , Aged , Anticholesteremic Agents/adverse effects , Azetidines/adverse effects , Drug Combinations , Ezetimibe , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Male , Middle Aged , Simvastatin/adverse effects , Taiwan , Time FactorsABSTRACT
BACKGROUND: Although diabetes mellitus is known as a major risk factor for Klebsiella pneumoniae infection, the differences in clinical characteristics between community-acquired and nosocomial K. pneumoniae bacteremia in diabetic patients have been rarely reported. METHODS: This retrospective analysis enrolled 193 adult diabetic patients with K. pneumoniae bacteremia hospitalized between January 2005 and December 2006. The chi-squared test, analysis of variance (ANOVA), Student's t test, Fisher exact test, and Cox regression model were used for statistical analysis. RESULTS: Of the enrolled patients, 147 had community-acquired infections and 46 had nosocomial infections. Compared with the community group, the nosocomial group had higher rates of in-hospital mortality (41.3% vs. 18.4%, p=0.001), malignancy (50.0% vs. 19.0%, p<0.001), and leukopenia (21.7% vs. 5.4%, p=0.001) but had lower levels of serum C-reactive protein (124.3 mg/L vs. 188.7 mg/L, p=0.018) and HbA1c (8.1% vs. 9.5%, p=0.025). The rate of infection with the extended-spectrum ß-lactamase-producing strain (ESBL infection) in the nosocomial group was 11 times higher than that in the community group (45.7% vs. 4.1%, p<0.001). ESBL infection accounted for 53% of mortality in the nosocomial group. Pneumonia was more common in the nosocomial group, while local abscess was more common in the community group. The risk factors for mortality were pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio (creatinine level at admission/baseline). CONCLUSIONS: The nosocomial group had more ESBL infections which might account for the higher mortality. The HbA1c level during the course of infection did not affect the outcome. Pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio at admission were the risk factors for poor outcome.
Subject(s)
Community-Acquired Infections/microbiology , Cross Infection/microbiology , Diabetes Complications/microbiology , Klebsiella Infections/etiology , Klebsiella pneumoniae/isolation & purification , Adult , Aged , Aged, 80 and over , Bacteremia , Community-Acquired Infections/mortality , Cross Infection/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Successful human islet transplantation has led to insulin independence in type 1 diabetes. Dogs constitute an animal model for preclinical studies. We present our recent experience in canine islet isolation, cryopreservation and transplantation. METHODS: Twenty-seven pancreases from mongrel dogs, weighing 9-31 kg, were removed. Each pancreas was digested with collagenase, and then purified by density gradients. Islet number and purity were counted, and the viability of isolated islets was assessed in vitro by static incubation, perifusion study and in vivo transplantation into nondiabetic or diabetic nude mice. Additionally. freshly isolated islets were cryopreserved for 1 week, and then studied in vitro. RESULTS: The islet yield and purity were 121,000 +/- 135,000 IEQ per pancreas and 81.4 +/- 1.2%, respectively. The stimulation index (insulin release in 300 mg/dl glucose/insulin release in 100 mg/dl glucose) of the isolated islets was 6.6 +/- 1.9 (N = 7), and first and second phases of insulin secretion were demonstrated during perifusion study. After 1-week cryopreservation, the islet number decreased from 1,000 to 540 (N = 1) and insulin content decreased from 50.95 to 39.23 microg/150 islets (N = 1). These islets maintained their insulin response to high glucose. Four weeks after transplantation, the grafts showed abundant beta-cells and significant insulin content. Normoglycemia was achieved in 14 of 23 diabetic recipients after transplantation with 2,000 freshly isolated islets. CONCLUSION: Canine islets isolated at our laboratory were viable and maintained their physiological function both in vitro and in vivo.