Incidence and characteristics of spontaneous platelet macro-aggregation in acute ischemic stroke.

Spontaneous platelet aggregation is a trigger for additional development of larger thrombi. Micro-aggregation is observed in 10% of diabetes approximately and blocked by P2Y12 inhibitors, whereas macro-aggregation is associated with overexpression of platelet α2-adrenoreceptors and is not blocked by conventional anti-platelet medicines. We examined the incidence of spontaneous platelet macro-aggregation (SPMA) in acute ischemic stroke and analyzed its clinical characteristics. Out of 665 consecutive acute ischemic strokes, SPMA was found in 10 patients (1.5%, one tenth of micro-aggregation) despite no detection in 588 control subjects. Types of ischemic stroke were 4 atherothrombotic, 4 cardioembolic, and 2 lacunar strokes. Stroke with SPMA exhibited higher (worse) values of modified Rankin Scales (mRS) at discharge (3.00 ± 0.53 vs 1.93 ± 0.07, p = 0.042 by Wilcoxon) compared with stroke without SPMA despite no difference at admission. The proportion of patients who were functionally independent (score 0-2 on the mRS) at discharge was lower in stroke with SPMA compared with stroke without SPMA (p < 0.05 by chi-square test; OR 3.60, 95% CI 1.08-12.03; RR 2.04, 95% CI 1.05-2.86). It was intriguing that severe (high magnitude) SPMA was observed in 4 atherothrombotic stroke. Although anti-platelet therapy underwent, the proportion of atherothrombotic patients who were functionally improved and independent at discharge was lower in the presence of SPMA compared with the absence of SPMA (p < 0.05 by chi-square test). The patients with SPMA were more likely to be older, having major disabilities, being less functionally improved during hospitalization, and being less functionally independent at discharge.

Serum Albumin, Body Mass Index, and Preceding Xa and P2Y12 Inhibitors Predict Prognosis of Recurrent Ischemic Stroke.

BACKGROUND: A third to half of recurrent stroke occur while on antiplatelet therapy, but no study has explored factors relating to prognosis of recurrent ischemic stroke. This study aimed to clarify the risk factors to determine the clinical outcome of recurrent ischemic stroke. METHODS: A total of 1,333 consecutive acute ischemic stroke patients (first n = 492, recurrent n = 841) were enrolled. We explored factors influencing the modified Rankin Scales (mRS) at discharge that included platelet aggregability, preceding medicines, and well-known risks of biochemical data using Chi-square test or Fisher's exact probability test. RESULTS: As to preceding medicines, the proportion of patients who were functionally independent (mRS 0-2) at discharge was higher in preceding P2Y12 inhibitor that suppressed ADP- and collagen-induced macro-aggregation of platelet and Xa inhibitor or warfarin in cardioembolic stroke, but lower in P2Y12 inhibitor and Xa inhibitor or warfarin in lacunar stroke compared with no medicine. Regardless of LDL-cholesterol and HA1c, the mRS at discharge ≤ 2 was increased in the third tertile of serum albumin and body mass index (BMI) in atherothrombotic stroke; serum albumin and high-density lipoprotein cholesterol (HDL-C) in lacunar stroke; and serum albumin, HDL-C and BMI in cardioembolic stroke. Logistic regression analysis identified the following independent predictors for clinical outcome: serum albumin, HDL-C, BMI, and preceding Xa inhibitor and P2Y12 inhibitor. CONCLUSION: Regardless of well-known risk factors such as diabetes and high LDL-C, preceding treatment for Xa inhibitor or P2Y12 inhibitor, serum albumin, HDL-C, and BMI were associated with prognosis in recurrent ischemic stroke.

Hypocholesterolemic Effect of Blackcurrant (Ribes nigrum) Extract in Healthy Female Subjects: A Pilot Study.

Blackcurrant extract (BCE) ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can prevent lipid abnormalities in healthy individuals. Lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined the effects of BCE administered for 29 days on serum lipids in young healthy women. Blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in the serum were separated using a gel-permeation high-performance liquid chromatography method to measure the triacylglycerol and cholesterol levels in lipoproteins. There were no effects on lipids on day 4 of BCE intake, but the total cholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL) cholesterol, small VLDL cholesterol, and large low-density lipoprotein cholesterol were significantly decreased. These results suggest that the daily intake of BCE has a hypocholesterolemic effect in healthy women, and that it is effective in preventing atherosclerosis.

Factors Influencing Quality of Life in Stroke Patients: Focus on Eating Habits.

BACKGROUND: Adherence to healthy lifestyle factors has been shown to improve outcomes after stroke. This study aimed to identify lifestyle factors about eating habits that may affect the quality of life (QOL) in elderly stroke patients. METHODS: Fifty elderly patients with a first-ever stroke were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Lifestyle factors about eating habits were collected using questionnaires (Questions 1-17) for the intake of salt, calcium, magnesium, potassium, taurine, fiber, and protein, and the frequency of breakfast. RESULTS: QOL of physical, communication, and psychosocial subdomains was better in the low (healthy) tertile of poststroke eating habits (Questions 1-17) compared with the high tertile of post-troke eating habits (Questions 1-17). This relationship appeared in eating habits except for salt intake but not in eating habits of salt intake and directly measured salt intake. Compared with prestroke eating habits score, poststroke eating habits score was decreased (improved) in 36 patients concerning eating habits of salt intake, but only in 12 patients concerning eating habits except for salt intake (P < .05 by chi-square test). Poststroke eating habits of calcium and magnesium were associated with better psychosocial QOL and better physical or energy QOL, respectively. CONCLUSIONS: Poststroke eating habits of calcium and magnesium were associated with QOL in elderly patients with a first-ever stroke. Since eating habits except for salt intake was poorly improved after stroke, intensive interventions regarding eating habits might be important.

Collagen-Induced Platelet Aggregates, Diabetes, and Aspirin Therapy Predict Clinical Outcomes in Acute Ischemic Stroke.

BACKGROUND: Aggregation of platelets is a trigger for additional development of larger thrombi. This study aimed to identify factors that may affect platelet aggregability and their role in clinical outcomes in acute ischemic stroke. METHODS: Consecutive acute ischemic stroke patients (n = 352) who were transferred within 24 hours after its onset were enrolled. Peripheral venous blood was sampled to measure platelet aggregability and other parameters. RESULTS: Mean values of spontaneous small-sized platelet aggregates and collagen- or adenosine diphosphate (ADP)-induced large-sized aggregates were elevated in acute ischemic stroke. In atherothrombotic stroke (n = 178), collagen and ADP-induced large-sized aggregates were positively correlated with HbA1c, respectively. High incidence of the modified Rankin Scales (mRS) 5-6 at discharge was associated with diabetes complication (odds ratio [OR] 8.77, 95% confidence interval [CI] 1.32-57.56). The proportion of patients who were functionally independent (the mRS 0-2) at discharge was lower in the middle tertile of collagen and ADP-induced large-sized aggregates than their low tertile (OR 2.46, 95% CI 1.09-5.58; OR 2.43, 95% CI 1.05-5.59, respectively). Prestroke administration of aspirin recovered the proportion of independence at discharge (OR 0.25, 95% CI 0.06-0.99), and ameliorated incidence of the mRS 5-6. On logistic regression analysis, diabetes, HbA1c, collagen-induced large-sized aggregates, and prestroke administration of aspirin remained independent predictors of clinical outcomes in atherothrombotic stroke. In cardioembolic and lacunar stroke, no relations with clinical outcomes were found. CONCLUSIONS: High plasma level of HbA1c is involved in enhanced platelet aggregability in acute atherothrombotic stroke patients, and prestroke administration of aspirin may be beneficial to clinical outcomes.

Effects of Blackcurrant Anthocyanin on Endothelial Function and Peripheral Temperature in Young Smokers.

BACKGROUND: Blackcurrant anthocyanin (BCA) is expected to repair endothelial dysfunction, but it remains unclear whether beneficial effects are present in young healthy persons. This study examines whether supplements containing blackcurrant anthocyanin improve endothelial function and peripheral temperature in young smokers. METHODS: Young, healthy male nonsmokers (N group: n = 11; mean age 22 ± 2 years) and smokers (S group: n = 13; mean age 21 ± 1 years) were enrolled. A randomized and double-blind trial was designed to compare the effects of no supplement, a supplement containing 50 mg of blackcurrant anthocyanin (supplement A), and a supplement containing 50 mg of blackcurrant anthocyanin plus vitamin E (supplement B) on flow-mediated dilatation (FMD) and skin temperature. RESULTS: Under no supplement, FMD was unchanged during the 2 h period after smoking in the N group, whereas it was decreased during the 2 h period after smoking in the S group. Under the A supplement, FMD was decreased 1 h after smoking and returned to the baseline level 2 h after smoking in the S group. The skin temperature in the area of the foot dorsum was decreased in the S group after smoking compared with that in the N group, who did not smoke, whereas under A and B supplements, it was higher in the S group compared with that in the N group. CONCLUSIONS: BCA could attenuate the smoking-induced acute endothelial dysfunction and improve peripheral temperature in young smokers.

Novel anti-aging gene NM_026333 contributes to proton-induced aging via NCX1-pathway.

Diet-induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. Low serum bicarbonate is associated with high mortality in healthy older individuals. Recently, we demonstrated that both coupling factor 6 (CF6)-overexpressing transgenic (TG) and high salt-fed mice which had sustained intracellular acidosis, due to enhanced proton import through ecto-F1Fo complex and/or reduced proton export through Na+-K+ ATPase inhibition, displayed shortened lifespan and early senescence-associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In this study, we searched causative genes of proton-induced aging in CF6-overexpressing TG and high salt-fed mice. We discovered NM_026333 as a novel anti-aging gene which was downregulated in the heart and kidney in both types of mice. NM_026333 protein consists of 269 amino acids with transmembrane region (90-193aa). Induction of NM_026333 or recombinant protein rescued TG cells and CF6-treated human cells from aging hallmarks of impaired autophagy, genomic instability, and epigenetic alteration. NM_026333 protein directly bound plasma membrane Na+-Ca2+ exchanger 1 (NCX1) to suppress its reverse mode, and cancelled proton-induced epigenetic regression of Atg7 that was caused by H3K4 and H4K20 tri-methylation via suppression of demethylase and H4K5 acetylation via suppression of nuclear HDAC3-HDAC4-emerin system. NM_026333 also attenuated proton-induced impaired formation of autolysosome, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. These effects reappeared by NCX1 inhibitor. Furthermore, NCX1 inhibitor extended lifespan compared with vehicle-treatment in TG mice. This study will shed light on novel aging mechanism and provide implications in a target for anti-aging therapy.

Mitochondrial inhibitory factor protein 1 attenuates coupling factor 6-induced aging signal.

Coupling factor 6 (CF6) forces a counter-clockwise rotation of plasma membrane F1 Fo complex, resulting in proton import and accelerated aging. Inhibitory factor peptide 1 (IF1) suppresses a unidirectional counter-clockwise rotation of F1 Fo complex without affecting ATP synthesis. We tested the hypothesis that IF1 may attenuate CF6-induced aging signaling in CF6-overexpressing transgenic (TG) cells. In IF1-GFP overexpressing wild type (WT) cells, the diffuse peripheral staining of tubular mitochondria was observed with a dense widely distributed network around the nucleus. In TG cells, however, the only peri-nuclear network of fragmented mitochondria was observed at 24 h, but it was developed to a widely distributed mitochondrial network of tubular mitochondria at 72 h. TG cells displayed aging hallmarks of telomere attrition, epigenetic alterations, defective proteostasis, and genomic instability with a decrease in emerin and lamin and loss of heterochromatin. IF1 induction rescued TG cells from telomere attrition, expression of genomic instability with the increase in emerin and lamin, and that of epigenetic alterations with recovery of heterochromatin. In defective proteostasis, IF1 induction restored a potent peri-nuclear staining of autolysosomes compared with the baseline weak staining. The decrease in Atg7 was restored, whereas the increase in P62 was abolished. We conclude that genetic disruption of proton signals by IF1 induction suppressed CF6-induced expression of aging hallmarks such as telomere attrition, epigenetic alterations, defective proteostasis, and genomic instability. Given the widespread biological actions of CF6, the physiological and pathological actions of IF1 may be complex.

Intracellular protons accelerate aging and switch on aging hallmarks in mice.

Diet-induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. The serum bicarbonate level is an independent predictor of chronic kidney disease progression. We investigated whether proton accelerates aging by analyzing both coupling factor 6-overexpressing transgenic (TG) and high salt-fed mice which display sustained intracellular acidosis, due to enhanced proton import through ecto-F1 Fo complex and/or reduced proton export through Na+ -K+ ATPase inhibition. Both types of mice displayed shortened lifespan and early senescence-associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In chronic intracellular acidosis mice, autophagy was impaired by regression of Atg7, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. The increase in histone 3 trimethylation at lysine 4 (H3K4me3) and H4K20me3 and the decrease in H3K9me3 and H3K27me3 were observed in the heart and kidney obtained from both TG and high salt-fed mice. The decrease in lamin A/C, emerin, and heterochromatin protein 1α without changes in barrier-to-autointegration factor and high-mobility group box 1 was confirmed in TG and high salt-fed mice. Suppression of nuclear histone deacetylase 3-emerin system is attributable to epigenetic regression of Atg7 and H4K5 acetylation. These findings will shed light on novel aging and impaired autophagy mechanism, and provide implications in a target for antiaging therapy.

Spontaneous Micro-Aggregation of Platelets Predicts Clinical Outcome in Acute Ischemic Stroke.

BACKGROUNDS: Spontaneous micro-aggregation of platelets (SMAP) is frequently observed in stroke patients and is a trigger for the additional development of larger thrombi. We tested the hypothesis that SMAP may predict clinical outcome in acute ischemic stroke patients. METHODS AND RESULTS: Consecutive acute ischemic stroke patients (n = 358) who were transferred to our hospital within 24 hours after its onset were enrolled. Peripheral venous blood was sampled to measure various parameters when they arrived. SMAP was correlated with plasma brain natriuretic peptide and diastolic blood pressure positively, and with serum albumin and body weight negatively. Multivariable Cox regression analysis showed that only serum albumin was an independent predictor of the SMAP (P = .0023). The proportion of patients who were functionally independent (score 0-2 on the modified Rankin Scales) at discharge was lower in the third tertile of SMAP (higher level) as compared with the first and the second tertiles in ischemic stroke (odds ratio [OR], 5.76; 95 % confidence interval [CI], 3.31-10.05; P < .0001) and atherothrombotic stroke (P = .02 by chi-square test). The lower proportion of patients achieving independence was found in the first tertile of serum albumin (lower level) as compared with the second and third tertiles in ischemic (OR, 4.60; 95% CI, 2.66-7.95; P < .0001), atherothrombotic, and cardioembolic stroke (P = .004 and P < .0001 by chi-square test). On logistic regression analysis, SMAP and serum albumin remained independent predictors of poor outcome in ischemic stroke. CONCLUSIONS: SMAP within 24 hours after stroke onset is a novel independent predictor of clinical outcome in acute ischemic stroke patients.

Are Online Simulations for Radiation Emergency Medical Preparedness Less Effective in Teaching Than Face-to-Face Simulations?

OBJECTIVE: The study clarified differences in understanding and satisfaction between face-to-face and online training on radiation emergency medical preparedness (REMP) training. METHODS: The training was held at Hirosaki University between 2018 and 2022, with 46 face-to-face participants and 25 online participants. RESULTS: Face-to-face training was significantly more understandable than online for the use of the Geiger counter (P < 0.05), but the educational effect of virtual reality (VR) was not significantly different from the actual practice. For the team exercise of taking care of the victims, online resulted in a significantly higher understanding (P < 0.05). CONCLUSIONS: Interactive exercises can be done online with equipment sent to learners, and VR is also as effective. The use of videos was more effective for first-timers to learn the practical process from a bird's-eye view, especially for team-based medical procedures.

Service-Learning Experiences Related to Health Support Activities for Residents Who Have Returned Home after Evacuation Due to a Radiation Disaster.

Hirosaki University has regularly offered health support activities to residents of X town in Fukushima, and thus, some interactive benefits are expected as a service-learning experience for nursing students. This study aimed to clarify the experiences of students who participated in service-learning and consider which methods and content were effective. In total, 52 nursing students were recruited into the program, which was held from 2018 to 2021. The roles of students included assisting in health consultations related to a radiation disaster. Questionnaires designed by researchers with experience in risk communication programs were conducted on the students after the program, and included the reasons why they joined, their most memorable experiences, and their opinions regarding required support for residents. The data were analyzed by content analysis. The nursing students thought about the health of residents through health support activities in the affected areas. Furthermore, by communicating with residents via on-site service-learning, they could experience the humanity of the residents and the current status of the affected areas, learn the importance of person-to-person relationships, and think about reconstruction. Thus, service-learning was found to be effective and to offer substantial benefits for both residents and students in affected areas.

Training of Medical Responders to Nuclear Disaster: Hybrid Program in the COVID-19 Pandemic.

OBJECTIVE: The spread of COVID-19 has made it difficult to provide training in medical treatment in a radiation disaster. In this study, we will examine the effects and challenges of using a hybrid approach that combines online and face-to-face components. METHODS: A total of 5 face-to face and 25 online medical staff participated in the training program. This program was conducted by using multiple cameras for live coverage, while protective clothing and decontamination kits had been sent in advance to the participants so that they could experience face-to-face and online learning at the same time. RESULTS: Participants reported a high level of satisfaction and achievement with the style of delivery. They also experienced problems such as fatigue due to long hours, and dissatisfaction with the debriefing. CONCLUSIONS: In designing new online training, it is necessary to consider the quantity and content of the program, and to take participant fatigue into consideration.

Pre-stroke habitual prolonged sleep as a predictor for post-stroke sleep quality, stroke-related quality of life, and lifestyle values.

BACKGROUND: Prolonged sleep is a higher stroke risk, but post-stroke prolonged sleep facilitates stroke recovery. No study has explored the relationship between pre- and post-stroke prolonged sleep and their involvement in stroke-related quality of life (QOL).This study aimed to clarify the role of pre- and post-stroke prolonged sleep in QOL and sleep quality during hospitalization. METHODS: Fifty-one subacute stroke inpatients were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Sleep quality and lifestyle values were assessed by original questionnaires. RESULTS: Patients in pre-stroke prolonged sleep > 8 h had a higher incidence of post-stroke poor sleep quality than those belonging to the normal or shorter hours (OR 5.33, 95% CI 1.30-21.84, p = 0.047). In addition, pre-stroke prolonged sleep was associated with lower scores of psychosocial QOL and lifestyle values of "accepting disability; caring about what other people think of what you do". In contrast, post-stroke prolonged sleep was associated with the lower risk of post-stroke poor sleep quality (OR 0.27, 95% CI 0.08-0.86, p = 0.045). Post-stroke high sleep quality had higher (better) scores of physical and energy QOL, and lifestyle values of "caring about what other people think of what you do; having some places to go out after discharge" compared with post-stroke poor sleep quality. Post-stroke prolonged sleep was derived from pre-stroke not prolonged sleep rather than pre-stroke prolonged sleep (p = 0.039, Chi-square test). CONCLUSIONS: Pre-stroke prolonged sleep is associated with a higher incidence of post-stroke poor sleep quality and lower scores of QOL and lifestyle values after stroke.

Quantitative assessment of radiodermatitis through a non-invasive objective procedure in patients with breast cancer.

Assessment of skin condition is necessary for providing advice regarding skin self-care to patients with breast cancer who have undergone radiation therapy. Acute and chronic phases of radiodermatitis were analyzed in patients using objective assessment tools in the present study. A total of 18 women who received radiation therapy for breast cancer were enrolled in the present study and their skin surface temperature (SST), hydration level of the skin surface (HL), melanin intensity (MI) and erythema intensity (EI) were measured prior to radiation therapy and six months thereafter. Furthermore, skin condition was assessed using the Common Terminology Criteria for Adverse Events (CTCAE). EI and MI levels at the irradiated site peaked upon the completion of radiation therapy and declined to baseline at 6 months. In contrast, SST levels were elevated at the irradiated site during radiation therapy (P<0.05) and plateaued after its completion. The same parameters in non-irradiated control sites remained unchanged during the study period. HL reached the minimum in irradiated and non-irradiated sites upon completion of radiation therapy. Although HL returned to baseline in the non-irradiated site 6 months after radiation therapy, it remained low in the irradiated site. No relationship between the CTCAE and EI level was observed. In conclusion, the present study demonstrated that objective assessment tools, including SST and EI levels, were useful for assessing skin condition during radiodermatitis. The combination of the CTCAE and objective assessment tools will enable a more accurate assessment of radiodermatitis.

Nutritional regulation of coupling factor 6, a novel vasoactive and proatherogenic peptide.

High sodium, high glucose, and obesity are important risk factors for age-related diseases such as cardiovascular disease (CVDs), stroke, and cancer. Coupling factor 6 (CF6) is released from vascular endothelial cells and functions as a circulating peptide that inhibits prostacyclin and nitric oxide generation by intracellular acidosis. High glucose elevates CF6 by activation of protein kinase C and p38 mitogen-activated protein kinase, whereas CF6 causes type 2 diabetes mellitus, resulting in a high glucose vicious cycle. Low glucose increases inhibitory factor peptide 1, an endogenous inhibitor of CF6. High salt intake increases CF6 through nuclear factor κB signaling, whereas CF6 induces salt-sensitive hypertension and salt-induced congestive heart failure. Oral administration of vitamin C cancels salt-induced increase in CF6, and estrogen replacement leads to the delayed onset of CF6-induced salt-sensitive hypertension and the rescue from cardiac systolic dysfunction. Because CF6 contributes to the onset of CVDs, nutritional regulation of CF6 will shed light on the understanding of preventive strategy and mechanisms for CVDs and a target for therapy.