Correlation between Automated Quantification of Lung Perfusion Blood Volume (PBV) and Pulmonary Artery Pressure

Purpose: Dual-energy CT (DECT) can be used for quantification of lung perfusion blood volume (PBV), allowing objective evaluation. However, no reports have investigated pulmonary perfusion correlating with pulmonary artery pressure (PAP) in patients with chronic pulmonary diseases. The purpose was to evaluate automated quantification of the lung PBV using dual-energy CT, and its correlation with PAP. Methods: 274 patients who underwent echocardiography within two weeks also underwent CT. The population was divided into high (&ge;40 mmHg) and low (<40 mmHg) estimated systolic PAP (sPAP) groups (n = 63 and n = 211, respectively). We retrospectively eva-luated the lung PBV using Syngo software, and correlations between the lung PBV and estimated sPAP. Results: Lung PBV values were 25.0 ± 9.6 and 29.0 ± 9.3 Hounsfield units (HU) in high and low sPAP groups, respectively, with a significant difference between them (p = 0.003). In the high sPAP group with underlying lung diseases (n = 15), chronic thromboembolism (n = 25), pulmonary artery stenosis (n = 12), and left heart failure (n = 11), using the Dana Point classification system, lung PBV values were 18.6 ± 1.6, 25.1 ± 4.5, 25.8 ± 4.5, and 32.7 ± 9.4 HU, respectively. There were significant differences in quantification of the lung PBV among them. The mean sPAP of subjects with left heart failure was significantly higher than in the others. In subjects with left heart failure, a positive correlation between the lung PBV value and sPAP was noted (R = 0.721, p < 0.0001). Conclusions: Automated quantification of the lung PBV may estimate the high sPAP. The lung PBV may contribute to clarifying the etiology of a high PAP due to left heart failure.

Changes in Blood Volume and Colloid Osmotic Pressure during Fluid Absorption in Patients Undergoing Endoscopic Urosurgery: An Observational Study

Background and Objective: Anesthesiologists need to be familiar with perioperative changes in blood volume (BV);however, there is no standard method for repeated evaluation of BV over a short interval of time. We evaluated BV in the operation room using repeatable estimation methods. Method: Eighty-five ASA physical status I-II patients scheduled to undergo endoscopic urosurgery using irrigation fluid under general anesthesia at Nippon Medical School Hospital were included in this study. Irrigation with 3% sorbitol in water was commenced after establishment of general anesthesia and volumetric fluid balance, which was defined as control water balance (WB). Hematocrit (Hct), colloid osmotic pressure (COP), total protein (TP) and albumin (Alb) were repeatedly determined before and during anesthesia. BV was calculated using Allen’s formula and the changes in Hct, COP, TP and Alb. Main Outcome Measures: The main outcome was the accuracy of measuring changes in BV (△BV) calculated using the four serum markers. WB and the estimated △BV calculated from Hct, COP, TP and Alb (△BV-Hct, △BV-COP, △BV-TP, and △BV-Alb) were analysed using Pearson’s correlation coefficient test and Bland-Altman analysis. Results: Sixty-five patients were excluded. In the remaining 20 patients, there was a significant correlation between WB and △BV-COP (R2 = 0.72;P < 0.01), WB and △BV-TP (R2 = 0.59;P △BV-Alb (R2 = 0.57;P △BV-Hct (R2 = 0.06). Conclusion: △BV-COP, △BV-TP and △BV-Alb had correlation with WB. However, since COP can be measured repeatedly with simplified instruments under selected clinical circumstances, while TP and Alb cannot. COP is the most useful marker to measure △BV during perioperative period. Hct does not allow precise estimation of △BV.

Blood Volume Status in Patients with Chronic Fatigue Syndrome: Relation to Complaints

Four studies have compared a possible decrease in circulating blood volume in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients when compared to a healthy population. A more recent study has proven a correlation between RBC volume and OI in chronic OI patients without being diagnosed ME/CFS. The aim of the present study was to relate measured blood, RBC and plasma volumes (absolute and percent normalized) with the orthostatic intolerance complaints in ME/CFS patients. In the included 11 female ME/CFS patients, percentage decrease in normalized blood, RBC and plasma volume was similar for all three components: 83% &plusmn;12%, 83% &plusmn;12% and 83% &plusmn;11%, respectively. In patients with a clinical suspicion of OI (n = 7) all 3 volume components were significantly lower compared to patients without clinical suspicion of OI (n = 4). The difference percentage to normalized Blood volume was 77(7) vs 94(10) (p-value < 0.02), difference percentage to normalized RBC volume was 76(7) vs 96(10) (p-value < 0.01) and difference percentage to normalized plasma volume was 77(7) vs 93(10) (p-value < 0.05) in OI present versus absent. Plasma volumes were plotted against RBC volumes: the relation found was RBC volume = 0.99* Plasma volume + 1.55;p < 0.001;r = 0.90. In line with literature data, this pilot study shows that total blood volume and its components: RBC and plasma volume may be reduced in ME/CFS patients, especially in the presence of a clinical suspicion of OI.

Pattern of respiratory-induced changes in fingertip blood volume measured by light transmission

Respiratory-induced fluctuations in heart rate and arterial blood pressure have been intensively investigated, but there is little information on the effect of respiration on peripheral blood volume. In the current study, blood volume changes in the finger, obtained by light transmission measurements, were measured during regular breathing (6 s periods) and long breathing (12 s periods). Respiratory chest-circumference changes were simultaneously measured in order to associate the pattern of tissue blood volume change with the respiratory cycle. Sixteen subjects were studied, and in fourteen finger blood vol ume increased during inspiration and decreased during expiration in the long-breathing periods. In all 14 subjects the start of blood volume decrease was significantly delayed from the start of expiration by mean ± SD 1.00 ± 0.65 s (p < 0.001, range 0 - 2.3 s). The start of blood volume increase was significantly delayed from the end of expiration by 3.45 ± 1.76 s (p < 0.005). In eight, finger blood volume started to increase more than 2 s before the start of inspiration. For the 6 s breathing period, blood volume decreased during inspiration in five examinations, and increased in seven. The increase in peripheral blood volume during inspiration could be attributed to the higher abdominal pressure during inspiration, and to the decrease in sympathetic activity during inspiration and the subsequent vasodilatation. The decrease in peripheral blood volume during inspiration is probably due to the negative thoracic pressure during inspiration and its mechanical effect on thoracic vessels.

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.

Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Pretreatment red blood cell distribution width as a predictive marker for postoperative complications after laparoscopic pancreatoduodenectomy

BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various diseases.AIM To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively analyzed.Correlations between pretreatment RDW and clinicopathological characteristics and short-term outcomes were investigated.RESULTS Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal RDW.High pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification system.Subgroup analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe hemorrhage.High pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional index.CONCLUSION Pretreatment RDW was a special parameter for patients who underwent LPD.It was associated with malnutrition,severe inflammatory status and poorer short-term outcomes.RDW could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.

Refractory lipoatrophy treated with autologous whole blood injection:A case report

BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.

Autologous cord blood vs individualized supplements in autistic spectrum disorder:CORDUS study results

BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an equally ample effort to employ clinical studies for studying the ASD causes and cell therapies.Stem cells have yielded so far mixed results in clinical trials,and at patient level the results varied from impressive to no improvement.In this context we have administered autologous cord blood(ACB)and a non-placebo,material intervention repre-sented by an individualized combination of supplements(ICS)to ASD children.METHODS CORDUS clinical study is a crossover study in which both oral ICS and intravenous ACB were sequentially administered to 56 children;ACB was infused as an inpatient procedure.Treatment efficacy was evaluated pre-treatment and post-treatment at 6 months by an independent psychotherapist with Autism Treatment Evaluation Checklist,Quantitative Checklist for Autism in Toddlers and a 16-item comparative table score,after interviewing the children’s parents and therapists.Before and after each intervention participants had a set of blood tests including inflammatory,metabolic and oxidative markers,and the neuronal specific enolase.RESULTS No serious adverse reactions were noted during and after cord blood or supplement administration.ACB improved evaluation scores in 78%of children with age 3–7-years(n=28),but was much less effective in kids older than 8 years or with body weight of more than 35 kg(n=28;only 11%of children improved scores).ICS yielded better results than ACB in 5 cases out of 28,while in 23 kids ACB brought more improvement than ICS(P<0.05);high initial levels of inflammation and ferritin were associated with no improvement.Ample individual differences were noted in children's progress,and statistically significant improvements were seen after ACB on areas such as verbalization and social interaction,but not on irritability or aggressive behavior.CONCLUSION ACB has superior efficacy to ICS in ASD;high inflammation,ferritin,age and body weight predict less improvement;more clinical studies are needed for studying ACB efficacy in ASD.

Utility of Tissue Similarity Maps Based on Relative Cerebral Blood Volume for Grading Gliomas as Validated by Histological Results

INTRODUCTION Gliomas are the most common primary brain tumors.Grading gliomas is of significant clinical importance because treatment plans vary between high-and low-grade gliomas.Histopathologic grades of gliomas are closely related to microvasculature. Magnetic resonance （MR） perfusion-weighted imaging （PWI） is a technique to quantitatively evaluate tumor microenvironments by measuring cerebral blood volume （CBV）.

Rapid Multi-Wavelength Optical Assessment of Circulating Blood Volume Without a Priori Data

The measurement of circulating blood volume （CBV） is crucial in various medical conditions including surgery, iatrogenic problems, rapid fluid administration, transfusion of red blood ceils, or trauma with extensive blood loss including battlefield injuries and other emergencies. Currently, available commercial techniques are invasive and time-consuming for trauma situations. Recently, we have proposed high-speed multi-wavelength photoacoustic/photothermal （PA/PT） flow cytometry for in vivo CBV assessment with multiple dyes as PA contrast agents （labels）. As the first step, we have characterized the capability of this technique to monitor the clearance of three dyes （indocyanine green, methylene blue, and trypan blue） in an animal model. However, there are strong demands on improvements in PA/PT flow cytometry. As additional verification of our proof-of-concept of this technique, we performed optical photometric CBV measurements in vitro. Three label dyes--methylene blue, crystal violet simultaneous photometric determination of the and, partially, brilliant green--were selected for components of their two-dye mixtures in the circulating blood in vitro without any extra data （like hemoglobin absorption） known a priori. The tests of single dyes and their mixtures in a flow system simulating a blood transfusion system showed a negligible difference between the sensitivities of the determination of these dyes under batch and flow conditions. For individual dyes, the limits of detection of 3×10-6M-3×10-5M in blood were achieved, which provided their continuous determination at a level of 10-SM for the CBV assessment without a priori data on the matrix. The CBV assessment with errors no higher than 4% were obtained, and the possibility to apply the developed procedure for optical photometric （flow cytometry） with laser sources was shown.

On-line dynamic measurement of blood viscosity, hematocrit and change of blood volume

Objective: To develop an on line system for the measurement of blood viscosity and hematocrit. The dynamic changes of the macrovascular blood volumes, microvascular blood volumes and the total blood volume were observed by means of calculating from the testing result. Methods: Applying traditional viscosity measurement principle and specific wavelength optic density measurement method, an on line system for the measurement of blood viscosity and hematocrit was developed, and the A/D multifunctional board and the testing circuit were designed by ourselves. The system was validated by experiments both in vitro and in vivo. Therapeutic effects of hypertonic saline dextran solution (HSD) and Lactatic Ringers solution at the early stage after burn blast combined injury were compared by this method. Results: The results showed that the system has attained the goal of the design. The changes of the blood viscosity and hematocrit could be detected effectively and continuously. The changes of macrovascular, microvascular and total blood volume could be calculated approximately. Conclusions: The system and the method can continuously on line test the blood viscosity and hematocrit, and reveal the change and distribution of blood volumes more accurately and clearly in the therapy process by estimatng changes of the macrovascular, microvascular and total blood volumes, respectively. It has confirmed that HSD treatment could increase blood pressure and attenuate tissue edema by significantly increasing total blood volume, improving macrocirculatory and microcirculatory blood volumes. This study suggested that it could be desirable to develop an experiment technique based on the method mentioned above.

Study on the packed volume and the void ratio of idealized human red blood cells using a ?nite-discrete element method

Numerical simulations are performed to examine the packing behavior of human red blood cells(RBCs). A combined ?nite-discrete element method(FDEM) is utilized, in which the RBCs are modeled as no-friction and no-adhesion solid bodies. The packed volume and the void ratio of a large number of randomly packed RBCs are clari?ed,and the effects of the RBC shape, the mesh size, the cell number, and the container size are investigated. The results show that the packed human RBCs with normal shape have a void ratio of 28.45%, which is slightly higher than that of the ?at or thick cells used in this study. Such information is bene?cial to the further understanding on the geometric features of human RBCs and the research on RBC simulations.

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression

BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain brain regions,such as the cerebellum,highlighting a need for further research to support the current understanding of this disease.AIM To study brain changes in depressed adolescents.METHODS This study enrolled 34 adolescents with depression and 34 age-,sex-,and education-level-matched healthy control(HC)individuals.Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow(CBF)analysis,respectively.Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses.RESULTS The cerebellum,superior frontal gyrus,cingulate gyrus,pallidum,middle frontal gyrus,angular gyrus,thalamus,precentral gyrus,inferior temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals.These patients with depression further presented with a pronounced drop in CBF in the left pallidum(group=98,and peak t=-4.4324),together with increased CBF in the right percental gyrus(PerCG)(group=90,and peak t=4.5382).In addition,17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus(r=-0.5231,P<0.01).CONCLUSION The right PerCG showed structural and CBF changes,indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

Individual Differences in Blood Alcohol Concentrations after Moderate Drinking Are Mainly Regulated by Gastric Emptying Rate Together with Ethanol Distribution Volume

Blood alcohol concentration (BAC) differs greatly among individuals, even when people of the same sex and age drink alcohol under the same drinking conditions. In this study, we investigated the main factors involved in the internal reg-ulation of individual differences in BAC, focusing on the alcohol dehydrogenase 1B (ADH1B) genotype, blood acetal-dehyde concentration (BAcH), amount of habitual alcohol consumption, pharmacokinetic parameters of BAC, distribution volume of ethanol (Vd), and gastric emptying rate (GER) under the same drinking conditions. Twenty healthy Japanese males aged between 40 and 59 years old and having the aldehyde dehydrogenase 2 (ALDH2) genotype of ALDH 2*1/*2 were recruited for this study. The subjects were given 0.32 g ethanol/kg body weight in the form of commercially available beer (5%, v/v). The results showed that BAC-max differed greatly among individuals with a more than two-fold variation. When the BAC-time curve was compared among ADH1B genotypes (ADH1B*1/*1, *1/*2, and *2/*2), there were no differences in BAC among the genotypes. Although BAcH, monthly alcohol consumption, elimination rate of blood ethanol (β value) and ethanol disappearance rate from the body (EDR) can affect BAC, all of them had no correlations with BAC-max. However, Vd (liter/kg), ΔPlasma glucose concentration (ΔPGC = PGC30 min ? PGC0 min) and the serum concentration of gastric inhibitory polypeptide (GIP) did correlate with BAC-max. Model 2 in multiple linear regression analysis showed the optimal model for Vd and GIP with positive correlations with BAC-max. As GIP and ΔPGC are both reflected by gastric emptying rate (GER), we concluded that the individual differences in BAC after moderate drinking are mainly regulated by GER together with Vd. These findings demonstrate that together with body water content, the gastrointestinal tract plays an important role in the regulation of individual differences in BAC, involving first pass metabolism of ethanol.

Noninvasive method for determining blood pressure and contours of arterial and volume pulses

A noninvasive method for monitoring blood pressure, based on the principles established by Riva-Rocci and Korotkoff (K), is described;it furnishes, after a single compression-deflation cycle of the arm-encircling cuff, values of sys-tolic and diastolic blood pressures as well as the contours of the brachial arterial pulse and the corresponding volume pulse. K-sounds are detected by a single microphone situated in the cubital fossa, and the time-varying cuff pressure P(t) is read by a piezoresistive pressure sensor. The behavior of P(t) during deflation is resolved into two parts, P(t)=p(t)+b(t);p is a train of posi-tive going pulses (arising from arterial pulsa-tions), whereas b is a slowly changing baseline. Noise pulses in the microphone output are re-jected by using the observation that the first few K-sounds are emitted when p is close to a maxi-mum, and the last few when dp/dt is close to a maximum. The performance of the instrument is illustrated by showing how it copes with ambi-ent noise and involuntary manual perturbations of P, and by presenting contours of various pulses.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.