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.

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

In vivo label-free measurement of blood flow velocity symmetry based on dual line scanning third-harmonic generation microscopy excited at the 1700 nm window

Measurement of bloodflow velocity is key to understanding physiology and pathology in vivo.While most measurements are performed at the middle of the blood vessel,little research has been done on characterizing the instantaneous bloodflow velocity distribution.This is mainly due to the lack of measurement technology with high spatial and temporal resolution.Here,we tackle this problem with our recently developed dual-wavelength line-scan third-harmonic generation(THG)imaging technology.Simultaneous acquisition of dual-wavelength THG line-scanning signals enables measurement of bloodflow velocities at two radially symmetric positions in both venules and arterioles in mouse brain in vivo.Our results clearly show that the instantaneous bloodflow velocity is not symmetric under general conditions.

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.

Effect of sodium nitroprusside on the microrheological properties of red blood cells in di®erent media

Red blood cell(RBC)aggregation as well as their deformation signi¯cantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.

Clinical nursing value of predictive nursing in reducing complications of pregnant women undergoing short-term massive blood transfusion during cesarean section

BACKGROUND Cesarean hemorrhage is one of the serious complications,and short-term massive blood transfusion can easily cause postoperative infection and physical stress response.However,predictive nursing intervention has important clinical significance for it.AIM To explore the effect of predictive nursing intervention on the stress response and complications of women undergoing short-term mass blood transfusion during cesarean section(CS).METHODS A clinical medical record of 100 pregnant women undergoing rapid mass blood transfusion during sections from June 2019 to June 2021.According to the different nursing methods,patients divided into control group(n=50)and observation group(n=50).Among them,the control group implemented routine nursing,and the observation group implemented predictive nursing intervention based on the control group.Moreover,compared the differences in stress res-ponse,complications,and pain scores before and after the nursing of pregnant women undergoing rapid mass blood transfusion during CS.RESULTS The anxiety and depression scores of pregnant women in the two groups were significantly improved after nursing,and the psychological stress response of the observation group was significantly lower than that of the control group(P<0.05).The heart rate and mean arterial pressure(MAP)of the observation group during delivery were lower than those of the control group,and the MAP at the end of delivery was lower than that of the control group(P<0.05).Moreover,different pain scores improved significantly in both groups,with the observation group considerably less than the control group(P<0.05).After nursing,complications such as skin rash,urinary retention,chills,diarrhea,and anaphylactic shock in the observation group were 18%,which significantly higher than in the control group(4%)(P<0.05).CONCLUSION Predictive nursing intervention can effectively relieve the pain,reduce the incidence of complications,improve mood and stress response,and serve as a reference value for the nursing of women undergoing rapid mass transfusion during CS.

Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.

Exogenous insulin autoimmune syndrome:A case report and review of literature

BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.

The effectiveness of physical activity interventions on blood pressure in children and adolescents:A systematic review and network meta-analysis

Background:High blood pressure(BP)is a major contributor to mortality and cardiovascular diseases.Despite the known benefits of exercise for reducing BP,it is crucial to identify the most effective physical activity(PA)intervention.This systematic review and network meta-analysis(NMA)aimed to evaluate the available evidence on the effectiveness of various PA interventions for reducing BP and to determine their hierarchy based on their impact on BP.Methods:A search of PubMed,SPORTDiscus,PsycINFO,Web of Science,CINAHL,Cochrane,and Eric databases was conducted up to December 2022 for this systematic review and NMA.Randomized controlled trials and quasi-experimental studies targeting healthy children and adolescents aged 6-12 years old were included in this study.Only studies that compared controlled and intervention groups using PA or exercise as the major influence were included.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines.Three independent investigators performed the literature screening,data extraction,and risk of bias assessment.We used Bayesian arm-based NMA to synthesize the data.The primary outcomes were systolic BP and diastolic BP.We calculated the mean differences(MDs)in systolic BP and diastolic BP before and after treatment.Mean treatment differences were estimated using NMA and random-effect models.Results:We synthesized 27 studies involving 15,220 children and adolescents.PA combined with nutrition and behavior change was the most effective intervention for reducing both systolic BP and diastolic BP(MD=-8.64,95%credible interval(95%CI):-11.44 to-5.84;MD=-6.75,95%CI:-10.44 to-3.11),followed by interventions with multiple components(MD=-1.39,95%CI:-1.94 to-0.84;MD=-2.54,95%CI:-4.89 to-0.29).Conclusion:Our findings suggest that PA interventions incorporating nutrition and behavior change,followed by interventions with multiple components,are most effective for reducing both systolic BP and diastolic BP in children and adolescents.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Association of Thyroid Nodules with Various Elements in Urine and Blood Serum: A Case-Control Study

Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.

Dynamics in the Prevalence of Insulin Resistance between 2005 and 2023 in Type 2 Diabetics in South Kivu in the East of the Democratic Republic of Congo: Cross-Sectional Studies

Aim: Sub-Saharan Africa is undergoing an epidemiological transition responsible for a change in the metabolic profile in favour of insulin resistance. The aim of this study was to assess the dynamics of the prevalence of insulin resistance and associated risk factors in diabetic patients in the Democratic Republic of Congo between 2005 and 2023. Method: We measured fasting blood glucose and insulin levels and looked for metabolic syndrome parameters (2009 criteria) in type 2 diabetes patients in 2005-2008 (n = 176) and in 2018-2023 (n = 303). The HOMA model was used to measure insulin sensitivity and islet β-cell secretory function. Results: Between 2005 and 2013, the trend was towards an increase in the prevalence of insulin resistance (from 13.1% to 50.8%;p Conclusion: This present study shows an increase in insulin resistance in Congolese urban areas and a persistence of atypical diabetes mellitus in Congolese rural areas, confirming the particularity of the pathophysiology of the disease in African areas currently influenced by the epidemiological transition. Further studies using an appropriate methodology are required.

Identification of Key Blood Biomarkers Linking Di(2-ethylhexyl)Phthalate and Autoimmune Diseases in Adolescents Mice

Di(2-ethylhexyl)phthalate(DEHP)is a widely used plasticizer known for its reproductive developmental and immune system toxicity,mainly through esophagal,dermal,and respiratory exposure^([1-3]).Maternal exposure to DEHP during pregnancy can lead to adverse birth outcomes in offspring,including impacts on the thyroid system of adolescent offspring^([2-4]).

Sex Disparities in the Association of Blood Pressure Parameters and Arterial Sclerosis Risk

Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of CVD.Higher pulse wave velocity(PWV)measurements could reflect early progression of atherosclerosis.Based on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.

Impact of Regular Blood Donation on Body Iron Stores at Saudi Blood Donors

Introduction: One of the most frequent observations in long-term blood donation is chronic iron deficiency, which can develop into anaemia. The majority of blood screening methods employed by blood banks do not incorporate iron-status markers, which may result in potential subclinical iron deficiency. The aim of this study was to evaluate the effects of repeated blood donation on the levels of iron in the body and to guide blood donors in preventing the depletion of iron stores. Methods: Regular blood donors were categorised into distinct groups according to the number of donations they gave, and then the correlation between these groups and their bodies’ iron levels was examined. Different parameters were employed to identify iron deficiency and iron depletion in blood donors: serum ferritin, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total iron-binding capacity (TIBC), and serum iron. Results: The study included 300 individuals who regularly and willingly donated blood. There were no iron insufficiency cases among those donating blood for the first time (Group I). However, 15.5% of individuals who had donated once before (Group II) had ferritin levels of 15 - 30 μg/dl (ng/ml), indicating reduced iron stores. The rate increased to 18% (37 out of 206 individuals) among regular blood donors (Groups III, IV, and V). Iron deficiency (depletion) prevalence among regular blood donors in Groups III, IV, and V was 5.9% (12 out of 206) and 50.4% (100 out of 206). Donors who had donated blood most frequently had the lowest levels of haematological markers MCH, MCHC, and TIBC. Provide the p-values representing the differences between the means of MCV, MCH, iron, TIBC, and ferritin levels when comparing donor groups with the control group (Group I) based on the frequency of donations. Indicate statistically significant differences where the p-value is less than 0.0125. This significance level is adjusted based on the Bonferroni method, considering multiple independent tests. The result shows that the Iron parameter for the comparison between Group I and Group III and Group I and Group IV suggests a statistically significant difference in iron levels between these donor groups. Conclusion: The findings of this study show that a higher times of donations lads to a higher occurrence of depleted iron stores and subsequent erythropoiesis with iron deficiency by one donor from every three healthy donors. The iron and ferritin concentrations were within the normal range in group one (Control group) and reduced in the other four groups (G-2 to G-5). However, the level of haemoglobin remained within an acceptable range for blood donation. This outcome suggests that it may be necessary to reassess the criteria for accepting blood donors. The average serum ferritin levels were examined in all five groups (G-1 to G-5), both for males and females, and significant variations were seen among the groups under study. This study found that 35% of the individuals who regularly donate blood have iron-deficient anaemia (sideropenia). This suggests that it would be beneficial to test for serum ferritin at an earlier stage, ideally after three donations.

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.

Vitamin D, Parathyroid Hormone, Insulin Sensitivity and Islet β-Cell Secretory Function in Diabetic Patients from South Kivu in the Democratic Republic of Congo: Cross-Sectional Study

Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.

Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

Heterogeneous patterning of blood-brain barrier and adaptive myelination as renewing key in gray and white matter

Background:Development and homeostasis of the brain are enabled through the precise control of the cell microenvironment by the blood-brain barrier(BBB),which interfaces between the brain parenchyma and the lumen of blood microvessels,and by the blood-cerebrospinal fluid barrier,which separates the cerebrospinal fluid from the blood vessels of the choroid plexus(Villabona-Rueda et al.,2019).Here,the focus will be on the BBB,the impairment of which is considered the earliest common denominator in neurovascular diseases.

Epinephrine also acts on beta cells and insulin secretion

In a recent review examining neurotransmitter modulation of insulin secretion,the significant impact of epinephrine was not addressed.Its primary action involves inhibiting insulin release via alpha-adrenergic receptors,thereby reducing the response to insulin secretion stimulators,through the activation of K+channels and resulting in membrane hyperpolarization in beta cells.