N‐Methyl‐d‐Aspartate Induces Cortical Hyperemia through Cortical Spreading Depression‐Dependent and ‐Independent Mechanisms in Rats

Objective: N‐methyl‐d ‐aspartate (NMDA) is a powerful cerebrovascular dilator in vivo. Cortical spreading depression (CSD) has recently been shown to contribute to the pial arteriolar dilation in mice. Our main aim was to examine the participation of CSD in the overall cerebrovascular response to NMDA in the rat. Methods: Anesthetized Wistar rats (eight weeks old) were equipped with a closed cranial window to allow topical application of NMDA (10^?5–10^?3 M) to the parietal cortex. Cortical blood flow (CoBF) under and outside the cranial window was simultaneously monitored by using a two‐channel laser‐Doppler flowmeter. CSDs were detected by recording the changes in the cortical DC potential. Results: Concentrations of 10^?4 and 10^?3 M of NMDA evoked single CSDs associated with rapid, transient hyperemia, followed by a sustained, but reduced, increase in CoBF. The latency and magnitude of the CoBF responses were dose dependent. The higher dose resulted in shorter latency (100±5* vs. 146±11 seconds, *P<0.05; mean±standard error of the mean) and larger overall flow response (77±12* vs. 28±3% from baseline) under, but not outside, the cranial window. Conclusions : NMDA elicits dose‐dependent increases in CoBF that are composed of CSD‐dependent and ‐independent components in rats.     

Association of interarm blood pressure difference with cardio‐cerebral vascular disease: A community‐based,cross‐sectional study

Interarm blood pressure difference (IAD) is a risk factor for peripheral artery disease and cardio‐cerebral vascular disease (CCVD). The current study examines the association of IAD with stroke and coronary heart disease in a Chinese community. A cross‐sectional study was conducted in Pudong New Area in Shanghai, China. A total of 10 657 residents aged 15 years and older were randomly selected through three‐stage sampling. Volunteers had systolic and diastolic blood pressure (BP) measured in both arms at recruitment, and IAD was defined in both arms as the absolute difference in BP. Medical records of study participants were reviewed by investigators to confirm measurements. Logistic regression models were used to assess the association between systolic interarm blood pressure difference (sIAD) and diastolic interarm blood pressure difference (dIAD) with stroke and coronary heart disease. Compared with dIAD <5 mm Hg, the multivariate adjusted odds ratio (OR) of stroke prevalence was 1.357 (95% CI 0.725‐2.542, P = 0.034) for dIAD ≥20 mm Hg and 1.702 (95% CI1.025‐2.828, P = 0.040) for dIAD between 15 and 19 mm Hg, and the multivariate adjusted OR of coronary heart disease prevalence was 1.726 (95% CI 1.093‐2.726, P = 0.019) for dIAD ≥20 mm Hg and 1.498 (95% CI 0.993‐2.261, P = 0.044) for dIAD between 15 and 19 mm Hg. The relationship between cardio‐cerebral vascular disease and dIAD was significant in a Chinese community population. Further cohort studies are needed to investigate the association of different levels of IAD with the incidence of cardiovascular and cerebrovascular diseases and subsequent mortality.     

Reliability of morning,before‐dinner,and at‐bedtime home blood pressure measurements in patients with hypertension

The authors evaluated differences in the reliability of home blood pressure measurements taken in the morning, before dinner, and at bedtime. Forty‐eight patients with hypertension (age range, 50–89 years; mean age, 76.4 years) measured their home blood pressure using a validated automatic information/communication technology‐based device for 14 consecutive days. Those days were divided into the first seven days (1–7) and the following 8 to 14 days (days 8–14) and compared systolic blood pressure (SBP) reliability in the two periods for each measurement time point. In Bland‐Altman analyses, morning SBP showed the least standard error of measurement (3.0 mm Hg). There were fixed biases in morning and before‐dinner SBP with average limits of agreement of 3.9 and 6.4 mm Hg, respectively. For at‐bedtime SBP, a random error was detected and the minimal detectable change was 13.8 mm Hg. The percentage of near‐maximal variation of morning SBP was the smallest at 18.1%. Morning SBP therefore provided the most reliable home blood pressure value in the day.     

A whole‐killed,blood‐stage lysate vaccine protects against the malaria liver stage

Although the attenuated sporozoite is the most efficient vaccine to prevent infection with the malaria parasite, the limitation of a source of sterile sporozoites greatly hampers its application. In this study, we found that the whole‐killed, blood‐stage lysate vaccine could confer protection against the blood stage as well as the liver stage. Although the protective immunity induced by the whole‐organism vaccine against the blood stage is dependent on parasite‐specific CD4⁺ T‐cell responses and antibodies, in mice immunized with the whole‐killed, blood‐stage lysate vaccine, CD8⁺, but not CD4⁺ effector T‐cell responses greatly contributed to protection against the liver stage. Thus, our data suggested that the whole‐killed, blood‐stage lysate vaccine could be an alternative promising strategy to prevent malaria infection and to reduce the morbidity and mortality of patients with malaria.     

Haptoglobin,alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania

Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co‐inheritance in SCA of alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co‐inheritance of these polymorphisms on CBFv in 601 stroke‐free Tanzanian SCA patients aged <24 years. Homozygosity for alpha‐thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild‐type (β‐coefficient ?16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha‐thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35–0·8] & RRR = 0·43 [95% CI:0·23–0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17–0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co‐inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha‐thalassaemia in reducing risk of abnormal CBFv.     

Expert Consensus Statement on achieving self‐sufficiency in safe blood and blood products,based on voluntary non‐remunerated blood donation (VNRBD)*

All countries face challenges in making sufficient supplies of blood and blood products available and sustainable, while also ensuring the quality and safety of these products in the face of known and emerging threats to public health. Since 1975, the World Health Assembly (WHA) has highlighted the global need for blood safety and availability. WHA resolutions 63·12, 58·13 and 28·72, The Melbourne Declaration on 100% Voluntary Non‐Remunerated Donation of Blood and Blood Components and WHO Global Blood Safety Network recommendations have reaffirmed the achievement of ‘Self‐sufficiency in blood and blood products based on voluntary non‐remunerated blood donation (VNRBD)’ as the important national policy direction for ensuring a safe, secure and sufficient supply of blood and blood products, including labile blood components and plasma‐derived medicinal products. Despite some successes, self‐sufficiency is not yet a reality in many countries. A consultation of experts, convened by the World Health Organization (WHO) in September 2011 in Geneva, Switzerland, addressed the urgent need to establish strategies and mechanisms for achieving self‐sufficiency. Information on the current situation, and country perspectives and experiences were shared. Factors influencing the global implementation of self‐sufficiency, including safety, ethics, security and sustainability of supply, trade and its potential impact on public health, availability and access for patients, were analysed to define strategies and mechanisms and provide practical guidance on achieving self‐sufficiency. Experts developed a consensus statement outlining the rationale and definition of self‐sufficiency in safe blood and blood products based on VNRBD and made recommendations to national health authorities and WHO.     

Validation of two watch‐type wearable blood pressure monitors according to the ANSI/AAMI/ISO81060‐2:2013 guidelines: Omron HEM‐6410T‐ZM and HEM‐6410T‐ZL

There is growing evidence of the clinical significance of daytime masked hypertension (MHT) and blood pressure (BP) variability (BPV). Recently, watch‐type wearable devices for self‐BP measurement have become available. Such devices might be promising tools to identify patients with daytime MHT or large BPV in their real‐life conditions. The present study aimed to validate the accuracy of the Omron HEM‐6410T‐ZM and the Omron HEM‐6410T‐ZL, which are automatic watch‐type wearable devices for self‐BP measurement, according to the American National Standards Institute, Inc/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060‐2:2013 guideline. Watches were held with the wrist at heart level. The mean differences between reference BPs and HEM‐6410T‐ZM readings were −0.9 ± 7.6/‐1.1 ± 6.1 mm Hg for systolic BP (SBP)/diastolic BP (DBP) for criterion 1, and −0.9 ± 6.8/‐1.1 ± 5.5 mm Hg for SBP/DBP for criterion 2. The mean differences between reference BPs and HEM‐6410T‐ZL readings were 2.4 ± 7.3/0.7 ± 7.0 mm Hg for SBP/DBP for criterion 1, and 2.4 ± 6.5/0.7 ± 6.5 mm Hg for SBP/DBP for criterion 2. The Omron HEM‐6410T‐ZM and the Omron HEM‐6410T‐ZL both fulfilled both validation criteria 1 and 2 of the ANSI/AAMI/ISO 81060‐2:2013 guidelines.     

Post‐Transplantation Immunoadsorption Can Be Withheld in ABO‐Incompatible Kidney Transplant Recipients

After ABO‐incompatible kidney transplantation, postoperative plasma exchange (PE) or immunoadsorption (IA) is performed per protocol or depending on postoperative A/B‐titers to prevent acute rejection. However, the need for postoperative PE or IA is not known. Since 2006, 30 consecutive patients received three standard postoperative IAs. Starting from 2009, the last 46 patients received only preoperative IA. Preoperative desensitization consisted of rituximab, tacrolimus, mycophenolate mofetil, prednisone and intravenous immunoglobulins. Antigen‐specific IA was performed pre‐operatively with the Glycosorb device. Biopsy‐proven acute rejections either antibody‐mediated (AMR) or mixed cellular and antibody‐mediated (MAR) within 3 months were recorded. The postoperative titer in patients with postoperative IA did not exceed 1:16 (IgG 1:4 [<2–16] median and range). The postoperative IgG titer was not significantly different after abandoning postoperative IA, although three patients had titers of 1:32 and one patient even 1:128. Rejections tended to be more frequent in the group with postoperative IA: 6 AMR and 3 MAR were recorded in 30 patients, vs. 4 AMR and 1 MAR in the 46 patients without postoperative IA (30 vs. 11%, P = 0.067). Baseline characteristics differed however: in the group with postoperative IA the vast majority had blood group O (87 vs. 52%, P = 0.003). Also, the IgG titer on the day of transplantation was higher (1:4 [<2–16] vs. 1:2 [<2–32], P = 0.007). All 14 patients with AMR and MAR rejections had postoperative IgG titers ≤1:16. Postoperative removal of A/B‐antibodies can be safely removed from the ABOi transplantation protocol using strict preoperative criteria for antibody lowering.     

The first study comparing a wearable watch‐type blood pressure monitor with a conventional ambulatory blood pressure monitor on in‐office and out‐of‐office settings

Wearable blood pressure (BP) monitoring devices which measure BP levels accurately both in and out of the office are valuable for hypertension management using digital technology. The authors have conducted the first comparison study of BPs measured by a recently developed wrist‐worn watch‐type oscillometric BP monitoring (WBPM) device, the “HeartGuide,” versus BPs measured by an ambulatory BP monitoring (ABPM) device, A&D TM‐2441, in the office (total of 4 readings alternately measured in the sitting position) and outside the office (30‐minutes interval measurements during daytime) in 50 consecutive patients (mean age 66.1 ± 10.8 years). The 2 BP monitoring devices were simultaneously worn on the same non‐dominant arm throughout the monitoring period. The mean difference (±SD) in systolic BPs (average of 2 readings) between WBPM and ABPM was 0.8 ± 12.8 mm Hg (P = .564) in the office and 3.2 ± 17.0 mm Hg (P < .001) outside the office. The proportion of differences that were within ±10 mm Hg was 58.7% in the office and 47.2% outside the office. In a mixed‐effects model analysis, the temporal trend in the difference between the out‐of‐office BPs measured by the two devices was not statistically significant. In conclusion, the difference between the WBPM and ABPM device was acceptable both in and out of the office.     

Performance of modified blood pressure‐to‐height ratio for diagnosis of hypertension in children: The CASPIAN‐V study

This study aimed to evaluate the accuracy and performance of modified blood pressure‐to‐height ratio (MBPHR) for identifying high blood pressure (HBP) in a large population of children. This multicentric cross‐sectional study was conducted on a nationally representative sample of 7349 Iranian students aged 7‐12 years living in 30 provinces in Iran. High systolic blood pressure and diastolic blood pressure were defined according to the 2017 American Academy of Pediatrics (AAP) guidelines. The BP‐to height ratio (BPHR) was calculated as BP (mmHg)/height (cm), MBPHR3 as BP (mmHg)/(height (cm) + 3 (13‐age)), and MBPHR7 as BP (mmHg)/(height (cm) + 7 (13‐age). The receiver‐operating characteristic curve analysis was used to evaluate the performance of these three ratios for identification of HBP in children compared to the 2017 AAP guidelines as the gold standard. Mean age of participants was 12.29 ± 3.15 years and 3736 (50.8%) were girls. The prevalence of HBP was 11.9% (11.5% in boys, 12.3% in girls). The area under the curve (AUC) was higher for MSBPHR3/MDBPHR3 (0.97/0.98) than MSBPHR7/MDBPHR7 (0.96/0.97) and SBPHR/DBPHR (0.96/0.95) for identifying high Systolic and diastolic BP. The optimal cut‐off points for MSBPHR3/MDBPH, MSBPHR7/MDBPHR7, and SBPHR/DBPHR were 0.76/0.50, 0.69/0.46, and 0.81/0.52 respectively. Negative predictive value was nearly perfect for three ratios (≥98%). Positive predictive value was higher for MBPHR3 (52.7%) than MBPHR7 (51.0%) and BPHR (39.8%). Overall, MBPHR3 had better performance than MBPHR7 and BPHR for identification of HBP in Iranian children and it may improve early hypertension recognition and control in primary screening.     

Structure‐oriented review of 14‐3‐3 protein isoforms in geriatric neuroscience

This review focuses on the possible relevance of 14‐3‐3 proteins in geriatric neuroscience. 14‐3‐3 proteins are mainly localized in the synapses and neuronal cytoplasm. These proteins regulate intracellular signal cascades for differentiation, development, growth, apoptosis and survival. Seven isoforms have so far been identified in mammals. The binding motifs and potential functions of 14‐3‐3 proteins are now recognized to have a wide range of functional relevance. First, we provide a brief summary of the molecular structure and multiple functions of 14‐3‐3 proteins. Second, we review the involvement of 14‐3‐3 proteins in common diseases of geriatric neurology, such as Alzheimer's disease and tauopathies, Parkinson's disease and α‐synucleinopathies, Huntington's disease and polyglutamine diseases, Creutzfeldt–Jakob disease and prion diseases, cerebral infarction, and atherosclerosis. Finally, we discuss the immunohistochemical localization of 14‐3‐3 proteins and its isoforms during the postnatal development of rat brains as a basis for understanding adult neurogenesis. The elucidation of the isoform‐dependent functions of 14‐3‐3 proteins with regard to brain development might be promising for the future development of novel therapeutic interventions for common diseases of geriatric neurology. Geriatr Gerontol Int 2012; ??: ??–??.     

Structured self‐monitoring of blood glucose reduces glycated hemoglobin in insulin‐treated diabetes

The aim of the preset study was to investigate the effectiveness of structured self‐monitoring of blood glucose (SMBG) in insufficiently controlled insulin‐treated diabetes. A total of 86 insulin‐treated patients were randomized to a routine testing group (RTG; n = 43) and a structured testing group (STG; n = 43). The STG used a chart to record seven‐point blood glucose (BG) profile on three consecutive days per month. The primary end‐point was the glycated hemoglobin (HbA1c) at 3 months and 6 months. There were no significant differences of HbA1c between the RTG and STG at 3 months. However, the STG had significantly improved HbA1c at 6‐month follow‐up compared with the RTG (P = 0.002). In the STG, HbA1c decreased by 0.5% from 7.9 (SD 0.5) to 7.4 (0.7)%, whereas it decreased by 0.1% in the RTG from 7.9 (0.5) to 7.8 (0.7)%. In the STG, 55% of the patients were willing to continue structured SMBG and they achieved a 0.7% decrease of HbA1c. The present findings suggest that structured SMBG significantly improves glycemic control.