Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan part 3: Inappropriate internal processing in the automatic diagnosis of electrocardiograms and its problems.

Computer diagnosis of electrocardiograms is widely used to provide useful information in clinical practice and medical checkups. However, it is common for users to be confused by the inappropriate diagnosis. We illustrate some examples of inappropriate automatic diagnoses and discuss the actual situation of inappropriate automatic processing and its problems.

Physicians' Resilience as a Positive Effect of COVID-19.

People devoid of COVID-19 may exhibit mental health problems, such as anxiety disorders, depression, panic attack, insomnia, emotional disorder, and suicidal actions. Healthcare workers (HCWs) may also exhibit these problems. Physicians should be careful an "at-risk" population. Physicians revealed higher levels of resilience than the popular workers. Humans with stronger resilience have lower feeling of anxiety and depression. We investigated the risk to physicians from an infected environment to infected patients during the pandemic. The social and psychological support of all HCWs, particularly physicians, is significant in the fight against this pandemic. Physicians working with patients with COVID-19 should set enough time to relax, sleep, and spend time with family. Resilience in physicians facing COVID-19 can induce post-traumatic growth in the future.

Increasing averaging beats improves the test accuracy on Holter-based late potentials in patients with myocardial infarction.

BACKGROUND: The prevalence of Holter-based late potentials (H-LPs) in cases of fatal cardiac events has increased. Although the noise level of H-LP is higher than that of conventional real-time late potential (LP) recording, a procedure to reduce the noise severity in H-LP by increasing the averaging beats has not been investigated. METHODS: We enrolled 104 patients with post-myocardial infarction (MI) and 86 control participants. Among the patients, 30 reported sustained ventricular tachycardia (VT), and the remaining 74 had unrecorded VT. H-LPs were measured twice in all groups to evaluate the efficacy of increasing the averaging beats for H-LPs. Thereafter, the average of LP was calculated at 250 (default setting), 300, 400, 500, 600, 700, and 800 beats. RESULTS: Across all three groups (MI-VT group, MI non-VT group, and control group), the noise levels significantly decreased in consonance with the increase in averaging beats. In the MI-VT group, the H-LP positive rate considerably increased with the increase in the averaging beats from 250 to 800 both at night and daytime. In the MI-VT group, the LP parameters significantly deteriorated, which led to a positive judgment corresponding to the increment of the averaged night and day beats. The H-LP positive rates were unchanged in the MI non-VT and control groups, while the LP parameters remained consistent, despite the increased averaging beats in the MI non-VT and control groups. CONCLUSION: Increasing the calculated averaging beats in H-LPs can improve the sensitivity of predicting fatal cardiac events in patients with MI.

Diurnal Variation in and Optimal Time to Measure Holter-Based Late Potentials to Predict Lethal Arrhythmia after Myocardial Infarction.

Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal variation, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing the diurnal variability in LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the observation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing the diurnal variability in LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals < 40 µV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45-9.71; p = 0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting the LP parameters in the MI-VT and control groups. In the non-VT group, the LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters, such as logpNN50. Conclusions: For Holter-based LP measurements, the test accuracy was higher when the LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate, were factors influencing diurnal variability. Increased parasympathetic activity or bradycardia may exacerbate Holter-based LP parameters.

Prognostic value of B-type natriuretic peptide for nursing- and healthcare-associated pneumonia and aspiration pneumonia in comparison with procalcitonin and A-DROP score: a prospective cohort study.

Background: Pneumonia in elderly patients who require nursing care is becoming more and more common among the aging populations of developed countries, and treatment is an important topic worldwide. A simpler prognostic indicator would be expected to improve the treatment of pneumonia. This single-center, prospective cohort study aimed to compare the usefulness of B-type natriuretic peptide (BNP), procalcitonin (PCT), and the A-DROP score, which have been reported to correlate with pneumonia prognoses, such as aspiration pneumonia (AP). Methods: We included patients who were admitted to the Kanazawa Medical University Himi Municipal Hospital with a diagnosis of either nursing- and healthcare-associated pneumonia (NHCAP) or AP between January 1, 2012 and July 31, 2019. We collected demographic, clinical, and laboratory characteristics and outcome data from electronic medical records, and calculated A-DROP scores. The primary outcome was 30-day mortality. We evaluated correlations with the primary outcome using the chi-square test, Fisher exact test, t-test, Cox-regression analysis, and receiver operating characteristic curve analysis. Results: Of the 1,215 patients with pneumonia, 297 were eligible for the study, of whom 37 (12%) died whin 30 days. After univariate analysis, we performed Cox proportional-hazards analysis for BNP, PCT, A-DROP score, albumin, C-reactive protein, and disseminated intravascular coagulation, which were significantly correlated with the primary outcome in univariate analysis. As a result, only BNP showed a significant correlation (P=0.008, 95% CI: 1.30-6.06). No significant correlation was obtained in PCT (P=0.529) and A-DROP score (P=0.107). Furthermore, we generated receiver operating characteristic curve to estimate the prognostic cut-off values of BNP for the primary outcome of NHCAP and AP. The optimal cut-off value of BNP for predicting death was 179.3 pg/mL (sensitivity 62.2%, specificity 76.2%, negative likelihood ratio 0.50%, positive likelihood ratio 2.61%). And, BNP yielded the highest area under the curve (0.72) in comparison with PCT (0.67) and A-DROP score (0.69). Conclusions: BNP may be a more clinically useful prognostic factor for NHCAP and AP than PCT or A-DROP score, and should be considered as a routine test at the beginning of these treatments.

Age-related reference intervals for ambulatory electrocardiographic parameters in healthy individuals.

Background: The advent of novel monitoring technologies has dramatically increased the use of ambulatory electrocardiography (AECG) devices. However, few studies have conducted detailed large-scale investigations on the incidence of arrhythmias over 24 h, especially ectopy, in healthy individuals over a wide age range. Objectives: This study aimed to investigate the incidence of arrhythmias detected using AECG and associated factors, in healthy individuals, over a wide age range. Methods: In this cross-sectional study, we performed AECG on 365 healthy volunteers (median [interquartile range]: 48 [36, 67], 20-89 years, 165 men) under free-running conditions for 24 h. Ultrasonic echocardiography and heart rate variability analysis were performed to explore the factors associated with the incidence of arrhythmias. Results: The 97.5th percentile of single ventricular ectopy (VE) was 149/day, 254/day, and 1,682/day in the 20-39-, 40-59- and 60-89-year age groups, respectively; that of single supraventricular ectopy (SVE) was 131/day, 232/day, and 1,063/day, respectively. Multivariate analysis revealed that aging was the only independent significant factor influencing the frequency of VE (ß = 0.207, P = 0.001). Age (ß = 0.642, P < 0.001), body mass index (BMI) (ß = -0.112, P = 0.009), and the root mean square of successive differences in RR intervals (ß = 0.097, P = 0.035) were factors significantly associated with SVE frequency. Conclusions: Age-specific reference intervals of VE and SVE in a large population of healthy participants over a wide age range were generated. VE and SVE increased with age; SVE was influenced by BMI and the aging-induced decrease in parasympathetic tone activity.

Personal factors and postoperative changes in the revised Venous Clinical Severity Score of varicose veins.

OBJECTIVE: The primary aim of this observational study was to measure the Revised Venous Clinical Severity Score (rVCSS) in patients treated for varicose veins (VVs) owing to saphenous vein reflux. Treatment was by endovenous thermal ablation (ETA) alone or by ETA and ambulatory phlebectomy (AP). A secondary aim was to determine whether participant characteristics and treatment methods affect rVCSS and how the score changes over time. METHODS: We enrolled 44 men with 55 treated legs and 79 women with 105 treated legs (bilateral cases, 23.1%). Patients were treated and evaluated from April 2016 to September 2020. All legs were treated by ETA, and participants were divided into three groups depending on AP treatment: E0 group (40 legs), no AP; EP1 group (101 legs), AP performed only at one site above or below the knee; and EP2 group (19 legs), AP performed both above and below the knee. The rVCSS was measured in the treated legs up to five times: preoperatively and on postoperative days (POD) 1, 7, 90, and 180. RESULTS: The mean age was 67.5 ± 11.24 years (range, 32-87 years). No significant differences in medical history or demographics or lifestyle were found between the groups. The mean preoperative rVCSS also was not different between groups (E0, 4.4 ± 0.3 points; EP1, 4.6 ± 0.2 points; and EP2, 5.4 ± 0.4 points; P = .14). Factors associated with less improvement in the rVCSS were a high body mass index (P = .046) and the occurrence of endovenous heat-induced thrombosis (P = .001), and factors associated with more improvement in the rVCSS were hypertension (P = .026), hyperuricemia (P = .022), and wearing compression stockings (P = .013). The rVCSS decreased strongly at POD1 and then gradually decreased until POD180. It was not significantly different between EP1 and EP2, but it improved significantly earlier in these two groups than in the E0 group. The rVCSS at POD180 was as follows: E0, 1.633 ± 0.233 points; EP1, 1.003 ± 0.148 points; and EP2, 0.982 ± 0.322 points. CONCLUSIONS: Factors associated with less improvement in the rVCSS are a high body mass index and the occurrence of endovenous heat-induced thrombosis. Hypertension, hyperuricemia, and wearing compression stockings are associated with greater improvements in the rVCSS. Patients treated with ETA and AP tend to improve earlier than patients treated by ETA alone, but all patients improve to nearly the same level within 6 months.

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ß1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (ß1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (ß1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

A new predictive tool consolidating CURB-65 with procalcitonin and albumin to assess short-term mortality in hospitalized elderly patients with infectious disease: A retrospective study of a patient cohort.

BACKGROUND: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb). METHOD: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died. RESULTS: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died. CONCLUSIONS: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease.

Ambulatory electrocardiographic markers predict serious cardiac events in patients with chronic kidney disease: The Japanese Noninvasive Electrocardiographic Risk Stratification of Sudden Cardiac Death in Chronic Kidney Disease (JANIES-CKD) study.

BACKGROUND: Noninvasive electrocardiographic markers (NIEMs) are promising arrhythmic risk stratification tools for assessing the risk of sudden cardiac death. However, little is known about their utility in patients with chronic kidney disease (CKD) and organic heart disease. This study aimed to determine whether NIEMs can predict cardiac events in patients with CKD and structural heart disease (CKD-SHD). METHODS: We prospectively analyzed 183 CKD-SHD patients (median age, 69 years [interquartile range, 61-77 years]) who underwent 24-h ambulatory electrocardiographic monitoring and assessed the worst values for ambulatory-based late potentials (w-LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT). The primary endpoint was the occurrence of documented lethal ventricular tachyarrhythmias (ventricular fibrillation or sustained ventricular tachycardia) or cardiac death. The secondary endpoint was admission for cardiovascular causes. RESULTS: Thirteen patients reached the primary endpoint during a follow-up period of 24 ± 11 months. Cox univariate regression analysis showed that existence of w-LPs (hazard ratio [HR] = 6.04, 95% confidence interval [CI]: 1.4-22.3, p = .007) and NSVT [HR = 8.72, 95% CI: 2.8-26.5: p < .001] was significantly associated with the primary endpoint. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT resulted in a lower event-free survival rate than did other NIEMs (p < .0001). No NIEM was useful in predicting the secondary endpoint, although the left ventricular mass index was correlated with the secondary endpoint. CONCLUSION: The combination of w-LPs and NSVT was a significant risk factor for lethal ventricular tachyarrhythmias and cardiac death in CKD-SHD patients.

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan: Part 2: Current status of inappropriate automated diagnosis is widely used electrocardiographs in Japan.

It is important to objectively grasp the current status of automated electrocardiogram (ECG) diagnosis. This report aimed to analyze and evaluate ECG records that our members have encountered as an inappropriate diagnosis in real-world clinical practices.

Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus: A retrospective study of a patient cohort.

ABSTRACT: Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group.

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan. Part 1: Nomenclature for diagnosis and abnormal findings.

As these terms should accurately represent the abnormal findings and conditions as much as possible, we propose to unify these terms into terminologies that are not confusing and easy to understand for everyone.

Diffuse large B cell lymphoma originating from the maxillary sinus with skin metastases: A case report and review of literature.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma (ML), accounting for 30%-40% of cases of non-Hodgkin's lymphoma (NHL) in adults. Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17% of all lymphomas. ML from the maxillary sinus (MS) is a particularly rare presentation, and is thus often difficult to diagnose. We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis. CASE SUMMARY: An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area. His medical history included splenectomy due to a traffic injury, an old right cerebral infarction from when he was 74-years-old, hypertension, and type 2 diabetes mellitus. A plain head computed tomography (CT) scan revealed a 3 cm × 3.1 cm × 3 cm sized left MS. On day 25, left diplopia and ptosis occurred, and a follow-up CT on day 31 revealed the growth of the left MS mass. Based on an MS biopsy on day 50, we established a definitive diagnosis of DLBCL, non-germinal center B-cell-like originating from the left MS. The patient was admitted on day 62 due to rapid deterioration of his condition, and a plain CT scan revealed the further growth of the left MS mass, as well as multiple systemic metastasis, including of the skin. A skin biopsy on day 70 was found to be the same as that of the left MS mass. We notified the patient and his family of the disease, and they opted for palliative care, considering on his condition and age. The patient died on day 80. CONCLUSION: This case suggests the need for careful, detailed examination, and for careful follow-up, when encountering patients presenting with a mass.

Successful Treatment with Percutaneous Balloon Kyphoplasty for Syndrome of Inappropriate Secretion of Antidiuretic Hormone Associated with Vertebral Compression Fracture: A Case Report.

BACKGROUND The etiology of syndrome of inappropriate antidiuretic hormone secretion (SIADH) is highly variable. With little evidence, much of the guidance and recommendations available for management are based on clinical judgement. Although percutaneous balloon kyphoplasty can effectively relieve the severe pain associated with osteoporotic vertebral compression fractures that do not respond to conventional treatments, the effect of balloon kyphoplasty on SIADH associated with vertebral compression fracture remains unknown. CASE REPORT A 72-year-old woman was admitted to our hospital due to severe pain associated with lumbar compression fracture and pain-related SIADH. Since her pain could not be relieved by analgesics, she underwent percutaneous balloon kyphoplasty, a minimally invasive procedure intended to relieve pain. After the surgery, the patient's pain almost completely disappeared and her sodium level was gradually corrected within 3 days without any adverse events. CONCLUSIONS Percutaneous balloon kyphoplasty is a novel treatment option for SIADH associated with vertebral compression fracture. In the case presented here, it rapidly reduced pain and disability and also improved severe pain-associated SIADH without adverse effects. It may offer an alternative to pain regimens consisting of drugs, such as duloxetine, pregabalin, and opioids, that may exacerbate SIADH and hyponatremia. This case suggests treatment for new-onset or worsening hyponatremia in patients with vertebral compression fracture.

Combined evaluation of ambulatory-based late potentials and nonsustained ventricular tachycardia to predict arrhythmic events in patients with previous myocardial infarction: A Japanese noninvasive electrocardiographic risk stratification of sudden cardiac death (JANIES) substudy.

BACKGROUND: Noninvasive electrocardiographic (ECG) markers are promising arrhythmic risk stratification tools for identifying sudden cardiac death. However, little is known about the usefulness of noninvasive ECG markers derived from ambulatory ECGs (AECG) in patients with previous myocardial infarction (pMI). We aimed to determine whether the ECG markers derived from AECG can predict serious cardiac events in patients with pMI. METHODS: We prospectively analyzed 104 patients with pMI (88 males, age 66 ± 11 years), evaluating late potentials (LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT) derived from AECG. The primary endpoint was the documentation of ventricular fibrillation or sustained ventricular tachycardia. RESULTS: Eleven patients reached the primary endpoint during a follow-up period of 25 ± 9.5 months. Of the 104 patients enrolled in this study, LP positive in worst values (w-LPs) and NSVT were observed in 25 patients, respectively. In the arrhythmic event group, the worst LP values and/or NSVT were found in eight patients (7.6%). The positive predictive and negative predictive values of the combined assessment with w-LPs and NSVT were 56% and 94%, respectively, for predicting ventricular lethal arrhythmia. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT had a poorer event-free period than negative LPs (p < .0001). In the multivariate analysis, the combined assessment of w-LPs and NSVT was a significant predictor of arrhythmic events (hazard ratio = 14.1, 95% confidence intervals: 3.4-58.9, p < .0001). CONCLUSION: Combined evaluation of w-LPs and NSVT was a powerful risk stratification strategy for predicting arrhythmia that can lead to sudden cardiac death in patients with pMI.

Combination effects of a fatty diet and exercise on the depressive state and cardioprotection in apolipoprotein E knockout mice with a change in RCAN1 expression.

OBJECTIVE: Regulator of calcineurin 1 (RCAN1) controls plasticity of the nervous system and depressive conditions by regulating brain-derived neurotropic factor (BDNF) and plays a crucial role in neural and cardiac pathways. The apolipoprotein E gene (ApoE) is a robust risk factor for progression of Alzheimer's disease. A fatty diet is considered detrimental for metabolic disorders, such as obesity and cardiovascular diseases. METHODS: We examined the neuronal and cardiac protective roles of RCAN1 in ApoE-/- mice that were fed a high- or low-fat diet with and without voluntary movement for 3 months. Organ weights, laboratory data, histology, RNA expression, and behavior were examined. RESULTS: A high-fat diet with exercise improved depressive function, as examined by the forced swimming test, and RCAN1 mRNA expression was induced in the hippocampus. A low-fat diet with exercise resulted in a reduced body weight, higher heart weight/body weight ratio, and lower circulating triglyceride levels compared with a low-fat diet without exercise. RCAN1 mRNA expression was increased in cardiomyocytes in ApoE-/- mice. CONCLUSIONS: The combination of a high-fat diet and exercise might reduce depressive function, whereas a low-fat diet with exercise leads to cardioprotection. Induction of RCAN1 expression might affect neuroplasticity and cardiac function.