Association between pre-treatment with statin and its inhibitory effect on the onset of coronary artery disease at the time of coronary computed tomography angiography: a new look at an old medication.

Coronary artery stenosis is often advanced by the time coronary computed tomography angiography (CCTA). Statins are the most important anti-lipidemic medication for improving the prognosis of coronary artery disease (CAD) patients. Although lipid-lowering therapy using statins appears to have been established as a method for preventing CAD, there remains the problem that CAD cannot be completely suppressed. In this study, we investigated whether pre-treatment with statin could significantly inhibit the onset of CAD when patients received CCTA for screening of CAD. The subjects were 1164 patients who underwent CCTA as screening for CAD. CAD was diagnosed when 50% or more coronary stenosis was present in the coronary arteries. Patient backgrounds were investigated by age, gender, body mass index, coronary risk factors [family history of cardiovascular diseases, smoking history, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, chronic kidney disease (CKD) or metabolic sydrome] and medications. Patients were classified into two groups according to the presence or absence of statin pre-administration during CCTA [statin (-) group (n = 804) and (+) group (n = 360)]. Compared with the statin (-) group, the statin (+) group was significantly older and had higher rates of family history, HTN, and DM. The statin (+) group had a significantly higher % CAD than the statin (-) group. Serum levels of low-density lipoprotein cholesterol (LDL-C) were significantly lower in the statin (+) group than in the statin (-) group. There was no significant difference in either high-density lipoprotein cholesterol levels or triglyceride levels between the two groups. Age, male gender, HTN, DM and pre-treatment with statin were all associated with CAD (+) in all patients. In addition, factors that contributed to CAD (+) in the statin (-) group were age, male gender, and DM, and factors that contributed to CAD (+) in the statin (+) group were age, smoking, HTN and % maximum dose of statin. At the time of CCTA, the statin (+) group had a high rate of CAD and coronary artery stenosis progressed despite a reduction of LDL-C levels. To prevent the onset of CAD, in addition to strict control of other coronary risk factors (HTN etc.), further LDL cholesterol-lowering therapy may be necessary.

Exploring perceptions toward home-care robots for older people in Finland, Ireland, and Japan: A comparative questionnaire study.

PURPOSE: To clarify potential users' perceptions toward the development and social implementation of home-care robots in Japan, Ireland, and Finland. METHODS: Unsigned, self-administered questionnaires were distributed to adults aged 65 or older, family caregivers, and home-care/health and social care professionals (HSCPs). A total of 1004 responses were collected. RESULTS: In Japan, many people were already familiar with robots in their daily lives. The most notable finding about their perspectives on home-care robots was related to safety. Moreover, 93.7 % of the Japanese respondents said, "If the user cannot decide whether to use a home-care robot, family members who know the user well should decide," followed by 76.4 % in Ireland and 83.1 % in Finland (p < .001). In Ireland, 81.8 % of the respondents said, "I want to help other people and society by participating in the research and development of home-care robots" (Japan: 69.9 %; Finland: 67.5 %) (p = .006). In Finland, many people had a negative impression of robots compared to the other two countries. Finland had the highest percentage (75.4 %) of respondents who said, "Health care professionals should be allowed to use secondary information collected by a home-care robot" (Japan and Ireland: 64 %) (p = .024). Moreover, Ireland and Finland emphasized the need to guarantee the entitlement to receive human care. CONCLUSIONS: Devising optimal strategies for the development and social implementation of home-care robots by incorporating various perspectives while valuing human dignity will require examination of each country's characteristics with respect to history, culture, policies, and values related to robots.

Gene expression analysis of Arc mRNA as a neuronal cell activity marker in the hippocampus and amygdala in two-way active avoidance test in rats.

INTRODUCTION: Immediate early genes are widely used as neuronal cell activity markers in neuroscience. The present study investigated the relationship between their expression and abnormality in context fear conditioning. METHODS: The learning test (two-way active avoidance test) was conducted in male rats administered with nonselective muscarinic antagonist scopolamine or selective dopamine D1-like receptor antagonist SCH 23390 at a dose level of 2.0 or 0.1mg/kg, respectively, for 4days. Expression levels of Arc and Fos mRNA in the hippocampus and amygdala were also evaluated on the second day of dosing by fluorescent in situ hybridization (FISH) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Scopolamine had no effect on avoidance rate, but decreased freezing in the two-way active avoidance test. SCH 23390 decreased avoidance rate and increased freezing. In FISH and RT-qPCR assays, scopolamine decreased Arc mRNA in the hippocampus and amygdala, whereas SCH 23390 increased Arc mRNA in the hippocampus. By contrast, scopolamine and SCH 23390 did not change Fos mRNA expression compared to Arc mRNA expression. DISCUSSION: The results of the learning test indicated that scopolamine or SCH 23390 respectively inhibited fear or context conditioning in rats. Furthermore, alteration of the expression of Arc mRNA but not of Fos mRNA in the hippocampus and amygdala of the brain was suggested to be a sensitive neuronal cell activity marker to detect behavioral abnormality in the two-way active avoidance test.

A Simple Algorithm for Predicting Bacteremia Using Food Consumption and Shaking Chills: A Prospective Observational Study.

BACKGROUND: Predicting the presence of true bacteremia based on clinical examination is unreliable. OBJECTIVE: We aimed to construct a simple algorithm for predicting true bacteremia by using food consumption and shaking chills. DESIGN: A prospective multicenter observational study. SETTING: Three hospital centers in a large Japanese city. PARTICIPANTS: In total, 1,943 hospitalized patients aged 14 to 96 years who underwent blood culture acquisitions between April 2013 and August 2014 were enrolled. Patients with anorexia-inducing conditions were excluded. INTERVENTIONS: We assessed the patients' oral food intake based on the meal immediately prior to the blood culture with definition as "normal food consumption" when >80% of a meal was consumed and "poor food consumption" when <80% was consumed. We also concurrently evaluated for a history of shaking chills. MEASUREMENTS: We calculated the statistical characteristics of food consumption and shaking chills for the presence of true bacteremia, and subsequently built the algorithm by using recursive partitioning analysis. RESULTS: Among 1,943 patients, 223 cases were true bacteremia. Among patients with normal food consumption, without shaking chills, the incidence of true bacteremia was 2.4% (13/552). Among patients with poor food consumption and shaking chills, the incidence of true bacteremia was 47.7% (51/107). The presence of poor food consumption had a sensitivity of 93.7% (95% confidence interval [CI], 89.4%-97.9%) for true bacteremia, and the absence of poor food consumption (ie, normal food consumption) had a negative likelihood ratio (LR) of 0.18 (95% CI, 0.17-0.19) for excluding true bacteremia, respectively. Conversely, the presence of the shaking chills had a specificity of 95.1% (95% CI, 90.7%-99.4%) and a positive LR of 4.78 (95% CI, 4.56-5.00) for true bacteremia. CONCLUSION: A 2-item screening checklist for food consumption and shaking chills had excellent statistical properties as a brief screening instrument for predicting true bacteremia.

Comparison of Nutritional Risk Scores for Predicting Mortality in Japanese Chronic Hemodialysis Patients.

OBJECTIVE: Protein energy wasting (PEW) is consistently associated with poor prognosis in hemodialysis (HD) patients. We compared the predictability of PEW as diagnosed by The International Society of Renal Nutrition and Metabolism criteria (PEWISRNM) and geriatric nutritional risk index (GNRI) for all-cause mortality in Japanese HD patients. As cut-off values for body mass index (BMI) for PEW have not been established in PEWISRNM for Asian populations, these were also investigated. DESIGN AND SUBJECTS: The nutritional status from 409 HD patients was evaluated according to ISRNM and GNRI criteria. To compare the predictability of mortality, C-index, net reclassification improvement (NRI) and integrated discrimination improvement were evaluated. RESULTS: During follow-up (median, 52 months; range, 7 months), 70 patients (17.1%) presented PEW according to ISRNM and 131 patients (32.1%) according to GNRI; in addition, 101 patients (24.7%) died. PEWISRNM and GNRI were identified as independent predictors of death. Addition of PEWISRNM and GNRI to a predictive model based on established risk factors improved NRI and integrated discrimination improvement. However, no differences were found between models including PEWISRNM and GNRI. When lowering the criterion level of BMI per 1 kg/m2 sequentially, PEWISRNM at BMI <20 kg/m2 maximized the hazard ratio for mortality. The model including PEWISRNM at BMI <20 kg/m2 improved NRI compared with the model including GNRI. CONCLUSION: PEWISRNM and GNRI represent independent predictors of mortality, with comparable predictability. The diagnostic criterion of BMI in the ISRNM for Japanese population might be better at <20 kg/m2 than at <23 kg/m2.

The domestic cat as a natural animal model of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is the most dominant neurodegenerative disorder that causes dementia, and no effective treatments are available. To study its pathogenesis and develop therapeutics, animal models representing its pathologies are needed. Although many animal species develop senile plaques (SP) composed of amyloid-ß (Aß) proteins that are identical to those found in humans, none of them exhibit neurofibrillary tangles (NFT) and subsequent neurodegeneration, which are integral parts of the pathology of AD. RESULTS: The present study shows that Aß accumulation, NFT formation, and significant neuronal loss all emerge naturally in the hippocampi of aged domestic cats. The NFT that form in the cat brain are identical to those seen in human AD in terms of their spatial distribution, the cells they affect, and the tau isoforms that comprise them. Interestingly, aged cats do not develop mature argyrophilic SP, but instead accumulate intraneuronal Aß oligomers in their hippocampal pyramidal cells, which might be due to the amino acid sequence of felid Aß. CONCLUSIONS: These results suggest that Aß oligomers are more important than SP for NFT formation and the subsequent neurodegeneration. The domestic cat is a unique animal species that naturally replicates various AD pathologies, especially Aß oligomer accumulation, NFT formation, and neuronal loss.

Senile plaques and cerebral amyloid angiopathy in an aged California sea lion (Zalophus californianus).

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA) consisting of ß-amyloid (Aß) are major features in the brain of Alzheimer's disease (AD) patients and elderly humans and animals. In this study, we report the finding of SPs and CAA in an aged sea lion (30 years), which is the first demonstration of AD-related pathological changes in a marine animal. Histologically, SPs were observed at the cerebral cortex, most frequently at the frontal lobe, with two morphologically different types: the small round type and the large granular type. Only the small round SPs were positive for Congo red staining. The SPs were equally immunoreactive to Aß40 and Aß42 and were mainly composed of Aß with an N-terminal pyroglutamate residue at position 3. Amyloid depositions at vessel walls were noted at the meninges and within the parenchyma. Interestingly, double immunofluorescence staining for Aß40 and Aß42 showed that the two subtypes were deposited segmentally in different parts of the vessel walls. The lesions observed in the sea lion suggest that Aß deposition is widely present in various animal species, including marine mammals; however, the peculiar deposits similar to cotton wool plaques and the specific pattern of CAA are characteristic features of this animal.

Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis.

Interleukin (IL)-15 is a pleiotropic cytokine that regulates the proliferation and survival of many cell types. IL-15 is produced by monocytes and macrophages against infectious agents and plays a pivotal role in innate and adaptive immune responses. This study analyzed the effect of IL-15 on fungicidal activity, oxidative metabolism and cytokine production by human monocytes challenged in vitro with Paracoccidioides brasiliensis (Pb18), the agent of paracoccidioidomycosis. Peripheral blood monocytes were pre-incubated with IL-15 and then challenged with Pb18. Fungicidal activity was assessed by viable fungi recovery from cultures after plating on brain-heart infusion-agar. Superoxide anion (O2⁻), hydrogen peroxide (H2O2), tumour necrosis factor-alpha (TNF-α), IL-6, IL-15 and IL-10 production by monocytes were also determined. IL-15 enhanced fungicidal activity against Pb18 in a dose-dependent pattern. This effect was abrogated by addition of anti-IL-15 monoclonal antibody. A significant stimulatory effect of IL-15 on O2⁻ and H2O2 release suggests that fungicidal activity was dependent on the activation of oxidative metabolism. Pre-treatment of monocytes with IL-15 induced significantly higher levels of TNF-α, IL-10 and IL-15 production by cells challenged with the fungus. These results suggest a modulatory effect of IL-15 on pro and anti-inflammatory cytokine production, oxidative metabolism and fungicidal activity of monocytes during Pb18 infection.

Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis

Interleukin (IL)-15 is a pleiotropic cytokine that regulates the proliferation and survival of many cell types. IL-15 is produced by monocytes and macrophages against infectious agents and plays a pivotal role in innate and adaptive immune responses. This study analyzed the effect of IL-15 on fungicidal activity, oxidative metabolism and cytokine production by human monocytes challenged in vitro with Paracoccidioides brasiliensis (Pb18), the agent of paracoccidioidomycosis. Peripheral blood monocytes were pre-incubated with IL-15 and then challenged with Pb18. Fungicidal activity was assessed by viable fungi recovery from cultures after plating on brain-heart infusion-agar. Superoxide anion (O2-), hydrogen peroxide (H2O2), tumour necrosis factor-alpha (TNF-α), IL-6, IL-15 and IL-10 production by monocytes were also determined. IL-15 enhanced fungicidal activity against Pb18 in a dose-dependent pattern. This effect was abrogated by addition of anti-IL-15 monoclonal antibody. A significant stimulatory effect of IL-15 on O2- and H2O2 release suggests that fungicidal activity was dependent on the activation of oxidative metabolism. Pre-treatment of monocytes with IL-15 induced significantly higher levels of TNF-α, IL-10 and IL-15 production by cells challenged with the fungus. These results suggest a modulatory effect of IL-15 on pro and anti-inflammatory cytokine production, oxidative metabolism and fungicidal activity of monocytes during Pb18 infection.

Event-related potentials in the frontal cortex, hippocampus, and cerebellum during a temporal discrimination task in rats.

The purpose of this study was to evaluate the roles of the frontal cortex, hippocampus, and cerebellum in timing and time perception using event-related potentials (ERPs) in rats. Rats were trained to discriminate between 2-s and 8-s auditory signal durations using a choice procedure. A simple reaction-time task using only the 2-s signal served as the control condition. In both tasks, ERPs were computed at stimulus onset and offset. Auditory ERPs were recorded from the frontal cortex, hippocampus, and cerebellum. The stimulus onset ERPs consisted of P2, N2, and P3-like components. Significantly greater amplitudes of the P3-like components were observed during the temporal-discrimination task when compared to the simple reaction-time task. At the stimulus offset, P2, N2, and P3-like components were elicited as well as the stimulus onset. Only in the frontal cortex was the P3-like component that appeared at the stimulus offset larger for the temporal-discrimination task than for the simple reaction-time task. These results suggest that the frontal cortex, hippocampus, and cerebellum contribute to interval timing in the seconds range.