Feasibility, reliability and satisfaction of (automated) capillary carcinoembryonic antigen measurements for future home-based blood sampling: the prospective CASA-I study.

AIM: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection. METHODS: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference. RESULTS: The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use. CONCLUSION: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling.

Novel buffer for long-term preservation of DNA in biological material at room temperature.

The collection and preservation of biological material before DNA analysis is critical for inter alia biomedical research, medical diagnostics, forensics and biodiversity conservation. In this study, we evaluate an in-house formulated buffer called the Forensic DNA Laboratory-buffer (FDL-buffer) for preservation of biological material for long term at room temperature. Human saliva stored in the buffer for 8 years, human blood stored for 3 years and delicate animal tissues from the jellyfish Pelagia noctiluca comb jelly Beroe sp., stored for 4 and 6 years respectively consistently produced high-quality DNA. FDL-buffer exhibited compatibility with standard organic, salting out and spin-column extraction methods, making it versatile and applicable to a wide range of applications, including automation.

[Box: see text].

Development and evaluation of a candidate reference measurement procedure for detecting 17α-hydroxyprogesterone in dried blood spots using isotope dilution liquid chromatography tandem mass spectrometry.

17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.

Improving blood pressure and dyslipidemia control by increasing health literacy in Croatia-missions 70/26 & Do you know what is your number.

PURPOSE: In 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia. MATERIALS AND METHODS: Croatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions - '70/26', and 'Do you know what is your number?' aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and 'School of Communication in Hypertension'. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies. CONCLUSION: We will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy.

Hypertension is the most compelling cause of death in Croatia with increasing prevalence.Still 50.1% of treated hypertensive patients and more than 70% of patients with dyslipidaemia in Croatia are uncontrolled.Programs 70/26 and Do you know your number aimed to achieve 70% and 50% control of hypertensive and dyslipidaemia patients, respectively, by 2026.To accomplish these goals, health literacy of healthcare workers, patients, and general population we will try to improve mostly using digital education and by organising schools of communication.

The Prothrombin-Prothrombinase Interaction.

The hemostatic response to vascular injury entails a sequence of proteolytic events where several inactive zymogens of the trypsin family are converted to active proteases. The cascade starts with exposure of tissue factor from the damaged endothelium and culminates with conversion of prothrombin to thrombin in a reaction catalyzed by the prothrombinase complex composed of the enzyme factor Xa, cofactor Va, Ca2+, and phospholipids. This cofactor-dependent activation is paradigmatic of analogous reactions of the blood coagulation and complement cascades, which makes elucidation of its molecular mechanism of broad significance to the large class of trypsin-like zymogens to which prothrombin belongs. Because of its relevance as the most important reaction in the physiological response to vascular injury, as well as the main trigger of pathological thrombotic complications, the mechanism of prothrombin activation has been studied extensively. However, a molecular interpretation of this mechanism has become available only recently from important developments in structural biology. Here we review current knowledge on the prothrombin-prothrombinase interaction and outline future directions for the study of this key reaction of the coagulation cascade.

Does Pelvic Floor Muscle Exercise Change the Hemodynamic Responses of the Inferior Vena Cava in Pregnant Women? A Prospective-Controlled Study.

INTRODUCTION AND HYPOTHESIS: This study was aimed at exploring the immediate impacts of pelvic floor muscle exercises (PFMEs) on various maternal physiological parameters in pregnant women. METHODS: The study included a total of 52 women, 26 pregnant (Pregnant group: 28.04±6.01 years; 26.83±3.81 kg/m2) and 26 nonpregnant (Control group: 29.42±5.73 years; 25.41±3.03 kg/m2) individuals. All women received PFME as follows: PFME was performed for 5 min (6-s holding contraction, 10 s of relaxation, 3 rapid PFM contractions). Evaluations were conducted before, immediately after, and 5 min post-exercise, with measurements including inferior vena cava (IVC) diameters and pulsatility index, blood pressure, oxygen saturation, and heart rates. Two-way analysis of variance was performed for group and time comparisons in repeated measurements. RESULTS: In both groups, the IVC collapsibility index values were lower 5 min after exercise, although this decrease, although clinically significant, did not reach statistical significance (p = 0.057). Post-exercise systolic blood pressure significantly decreased in both groups, whereas diastolic blood pressure decreased significantly in the pregnant group (p = 0.001, p = 0.023). CONCLUSIONS: The study found no statistically significant changes in the collapsibility index of the IVC after PFME but observed a clinically suggestive decrease. The clinical decrease in the collapsibility index can be interpreted as PFME in the supine position increasing venous return. Additionally, PFME was found not to alter maternal and fetal heart rates but contributed to the decrease in maternal systolic and diastolic blood pressure. Our study supports the view that the acute effects of PFME neither induce fetal stress nor pose maternal risks.

DNN-BP: a novel framework for cuffless blood pressure measurement from optimal PPG features using deep learning model.

Continuous blood pressure (BP) provides essential information for monitoring one's health condition. However, BP is currently monitored using uncomfortable cuff-based devices, which does not support continuous BP monitoring. This paper aims to introduce a blood pressure monitoring algorithm based on only photoplethysmography (PPG) signals using the deep neural network (DNN). The PPG signals are obtained from 125 unique subjects with 218 records and filtered using signal processing algorithms to reduce the effects of noise, such as baseline wandering, and motion artifacts. The proposed algorithm is based on pulse wave analysis of PPG signals, extracted various domain features from PPG signals, and mapped them to BP values. Four feature selection methods are applied and yielded four feature subsets. Therefore, an ensemble feature selection technique is proposed to obtain the optimal feature set based on major voting scores from four feature subsets. DNN models, along with the ensemble feature selection technique, outperformed in estimating the systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to previously reported approaches that rely only on the PPG signal. The coefficient of determination ( R 2 ) and mean absolute error (MAE) of the proposed algorithm are 0.962 and 2.480 mmHg, respectively, for SBP and 0.955 and 1.499 mmHg, respectively, for DBP. The proposed approach meets the Advancement of Medical Instrumentation standard for SBP and DBP estimations. Additionally, according to the British Hypertension Society standard, the results attained Grade A for both SBP and DBP estimations. It concludes that BP can be estimated more accurately using the optimal feature set and DNN models. The proposed algorithm has the potential ability to facilitate mobile healthcare devices to monitor continuous BP.

Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Drug targeting for brain malignancies is restricted due to the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which act as barriers between the blood and brain parenchyma. Certainly, the limited therapeutic options for brain malignancies have made notable progress with enhanced biological understanding and innovative approaches, such as targeted therapies and immunotherapies. These advancements significantly contribute to improving patient prognoses and represent a promising shift in the landscape of brain malignancy treatments. A more comprehensive understanding of the histology and pathogenesis of brain malignancies is urgently needed. Continued research focused on unraveling the intricacies of brain malignancy biology holds the key to developing innovative and tailored therapies that can improve patient outcomes. Lipid nanocarriers are highly effective drug delivery systems that significantly improve their solubility, bioavailability, and stability while also minimizing unwanted side effects. Surface-modified lipid nanocarriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lipid nanocapsules, lipid-polymer hybrid nanocarriers, lipoproteins, and lipoplexes) are employed to improve BBB penetration and uptake through various mechanisms. This systematic review illuminates and covers various topics related to brain malignancies. It explores the different methods of drug delivery used in treating brain malignancies and delves into the benefits, limitations, and types of brain-targeted lipid-based nanocarriers. Additionally, this review discusses ongoing clinical trials and patents related to brain malignancy therapies and provides a glance into future perspectives for treating this condition.

Quantitative and calculated estimated blood loss in cesarean deliveries for twin and singleton pregnancies: a retrospective analysis.

PURPOSE: This study retrospectively assessed blood loss during cesarean deliveries for twin and singleton pregnancies using two distinct methods, quantitative estimation measured during cesarean sections and hematocrit-based calculated estimation. METHODS: We included scheduled cesarean deliveries for twin or singleton pregnancies at ≥ 34 weeks of gestation. Quantitative blood loss was recorded based on the blood volume in the graduated collector bottle and by weighing the blood-soaked textiles during cesarean sections. The blood loss was calculated using the change in hematocrit levels before and after the cesarean delivery. RESULTS: We evaluated 403 cases including 44 twins and 359 singletons. Quantitative blood loss during cesarean section was significantly higher in twin pregnancies than that in singleton pregnancies (1117 [440] vs 698 [378] mL; p < 0.001). However, no significant differences were observed in the calculated blood loss between the two groups on the day after delivery (487 mL [692 mL] vs 507 mL [522 mL]; p = 0.861). On post-delivery days 4-5, twin pregnancies were associated with a significantly higher calculated blood loss than singleton pregnancies (725 [868] mL vs 444 [565] mL, p = 0.041). Although a significant moderate correlation between quantitative and calculated blood loss was observed in singleton pregnancies (r = 0.473, p < 0.001), no significant correlation was observed between twin pregnancies (r = 0.053, p = 0.735). CONCLUSION: Quantitative blood loss measurements during cesarean section may be clinically insufficient in twin pregnancies. Incorporating blood tests and continuous assessments are warranted for enhanced blood loss evaluation, especially in twin pregnancies, owing to the risk of persistent bleeding.

Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

PURPOSE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). CONCLUSION: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Heavy metal concentrations and clinical symptoms in patients diagnosed with schizophrenia related to cigarette smoking.

In our study, blood concentrations of lead (Pb), arsenic (As), and cadmium (Cd) and urine concentrations of thallium (Tl) were measured together with related symptoms of heavy metal poisoning in cigarette smoking volunteers diagnosed with schizophrenia, in cigarette smokers not diagnosed with schizophrenia, and in the control group of non-smokers and not diagnosed with schizophrenia volunteers. Our study was performed on 171 volunteers divided into the following subgroups: patients diagnosed with schizophrenia with at least 1 year of continuous cigarette smoking experience (56 participants), cigarette smokers not diagnosed with schizophrenia with at least one year of continuous smoking experience (58), and control group (not diagnosed with schizophrenia and non-smoking volunteers) (57). Smoking durations of cigarette smokers diagnosed with schizophrenia and cigarette smokers not diagnosed with schizophrenia are not similar (p = 0.431). Blood Pb, As, and Cd concentrations and urine Tl concentrations were the highest in the subgroup of cigarette smokers not diagnosed with schizophrenia, followed by the subgroup of cigarette smokers diagnosed with schizophrenia, and the control group. Only blood Pb concentrations were significantly higher (probability value p < 0.05) in the group of cigarette smokers not diagnosed with schizophrenia (5.16 µg/dL), comparing to the group of cigarette smokers diagnosed with schizophrenia (3.83 µg/dL) and to the control group (3.43 µg/dL). Blood Cd and As concentrations and urine Tl concentrations were significantly higher (p < 0.05) in cigarette smokers not diagnosed with schizophrenia than in the control group. The results revealed a statistically significant positive correlation (p < 0.001) in the cigarette smokers in the schizophrenia diagnosed group between blood Pb, blood As, and urine Tl concentrations and the duration of cigarette smoking.

LMBiS-Net: A lightweight bidirectional skip connection based multipath CNN for retinal blood vessel segmentation.

Blinding eye diseases are often related to changes in retinal structure, which can be detected by analysing retinal blood vessels in fundus images. However, existing techniques struggle to accurately segment these delicate vessels. Although deep learning has shown promise in medical image segmentation, its reliance on specific operations can limit its ability to capture crucial details such as the edges of the vessel. This paper introduces LMBiS-Net, a lightweight convolutional neural network designed for the segmentation of retinal vessels. LMBiS-Net achieves exceptional performance with a remarkably low number of learnable parameters (only 0.172 million). The network used multipath feature extraction blocks and incorporates bidirectional skip connections for the information flow between the encoder and decoder. In addition, we have optimised the efficiency of the model by carefully selecting the number of filters to avoid filter overlap. This optimisation significantly reduces training time and improves computational efficiency. To assess LMBiS-Net's robustness and ability to generalise to unseen data, we conducted comprehensive evaluations on four publicly available datasets: DRIVE, STARE, CHASE_DB1, and HRF The proposed LMBiS-Net achieves significant performance metrics in various datasets. It obtains sensitivity values of 83.60%, 84.37%, 86.05%, and 83.48%, specificity values of 98.83%, 98.77%, 98.96%, and 98.77%, accuracy (acc) scores of 97.08%, 97.69%, 97.75%, and 96.90%, and AUC values of 98.80%, 98.82%, 98.71%, and 88.77% on the DRIVE, STARE, CHEASE_DB, and HRF datasets, respectively. In addition, it records F1 scores of 83.43%, 84.44%, 83.54%, and 78.73% on the same datasets. Our evaluations demonstrate that LMBiS-Net achieves high segmentation accuracy (acc) while exhibiting both robustness and generalisability across various retinal image datasets. This combination of qualities makes LMBiS-Net a promising tool for various clinical applications.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. DISCUSSION: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin's antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Using clotted, pelleted blood samples for direct molecular detection of Bartonella spp. in small mammal wildlife surveillance studies.

OBJECTIVE: Bartonella are emerging bacterial zoonotic pathogens. Utilization of clotted blood samples for surveillance of these bacteria in wildlife has begun to supersede the use of tissues; however, the efficacy of these samples has not been fully investigated. Our objective was to compare the efficacy of spleen and blood samples for DNA extraction and direct detection of Bartonella spp. via qPCR. In addition, we present a protocol for improved DNA extraction from clotted, pelleted (i.e., centrifuged) blood samples obtained from wild small mammals. RESULTS: DNA concentrations from kit-extracted blood clot samples were low and A260/A280 absorbance ratios indicated high impurity. Kit-based DNA extraction of spleen samples was efficient and produced ample DNA concentrations of good quality. We developed an in-house extraction method for the blood clots which resulted in apposite DNA quality when compared to spleen samples extracted via MagMAX DNA Ultra 2.0 kit. We detected Bartonella in 9/30 (30.0%) kit-extracted spleen DNA samples and 11/30 (36.7%) in-house-extracted blood clot samples using PCR. Our results suggest that kit-based methods may be less suitable for DNA extraction from blood clots, and that blood clot samples may be superior to tissues for Bartonella detection.

Hsa-miR-134-5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells.

This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa-miR-134-5p, which targeted transforming growth factor ß-activated kinase 1-binding protein 1 (TAB1) gene, down-regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen-activated protein kinase (p38) in hsa-miR-134-5p-overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down-regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF-ß1) was down-regulated in hsa-miR-134-5p-overexpressed senescent EPCs and addition of TGF-ß1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa-miR-134-5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa-miR-134-5p expression level. In summary, hsa-miR-134-5p is involved in the regulation of senescence-related change of angiogenic activity via TAB1-p38 signalling and via TGF-ß1 reduction. Hsa-miR-134-5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC-derived hsa-miR-134-5p predicts cardiovascular risk.

Neurovascular coupling dysfunction associated with cognitive impairment in presbycusis.

The neuropathological mechanism underlying presbycusis remains unclear. This study aimed to illustrate the mechanism of neurovascular coupling associated with cognitive impairment in patients with presbycusis. We assessed the coupling of cerebral blood perfusion with spontaneous neuronal activity by calculating the correlation coefficients between cerebral blood flow and blood oxygen level-dependent-derived quantitative maps (amplitude of low-frequency fluctuation, fractional amplitude of low-frequency fluctuation, regional homogeneity, degree centrality). Four neurovascular coupling metrics (cerebral blood flow-amplitude of low-frequency fluctuation, cerebral blood flow-fractional amplitude of low-frequency fluctuation, cerebral blood flow-regional homogeneity and cerebral blood flow-degree centrality) were compared at the global and regional levels between the presbycusis group and the healthy control group, and the intrinsic association between the altered neurovascular coupling metrics and the neuropsychological scale was further analysed in the presbycusis group. At the global level, neurovascular coupling was significantly lower in the presbycusis group than in the control group and partially related to cognitive level. At the regional level, neurovascular biomarkers were significantly elevated in three brain regions and significantly decreased in one brain region, all of which involved the Papez circuit. Regional neurovascular coupling provides more information than global neurovascular coupling, and neurovascular coupling dysfunction within the Papez circuit has been shown to reveal the causes of poor cognitive and emotional responses in age-related hearing loss patients.

Multimodal evaluation of blood-brain barrier opening in mice in response to low-intensity ultrasound and a claudin-5 binder.

Background: The blood-brain barrier (BBB) is a major bottleneck in delivering therapeutics to the brain. Treatment strategies to transiently open this barrier include focused ultrasound combined with intravenously injected microbubbles (FUS+MB) and targeting of molecules that regulate BBB permeability. Methods: Here, we investigated BBB opening mediated by the claudin-5 binder cCPEm (a microorganismal toxin in a truncated form) and FUS+MB at a centre frequency of 1 MHz, assessing dextran uptake, broadband emission, and endogenous immunoglobulin G (IgG) extravasation. Results: FUS+MB-induced BBB opening was detectable at a pressure ≥0.35 MPa when assessed for leakage of 10 and 70 kDa dextran, and at ≥0.2 MPa for uptake of endogenous IgG. Treating mice with 20 mg/kg cCPEm failed to open the BBB, and pre-treatment with cCPEm followed by FUS+MB at 0.2 and 0.3 MPa did not overtly increase BBB opening compared to FUS+MB alone. Using passive cavitation detection (PCD), we found that broadband emission correlated with the peak negative pressure (PNP) and dextran leakage, indicating the possibility of using broadband emission for developing a feedback controller to monitor BBB opening. Conclusions: Together, our study highlights the challenges in developing combinatorial approaches to open the BBB and presents an additional IgG-based histological detection method for BBB opening.

С60 fullerene protective effect against the rat muscle soleus trauma.

Muscle trauma is one of the most common body injuries. Severe consequences of muscle trauma are ischemic injuries of the extremities. It is known that the intensification of free radical processes takes place in almost most acute diseases and conditions, including muscle trauma. C60 fullerene (C60) with powerful antioxidant properties can be considered a potential nanoagent for developing an effective therapy for skeletal muscle trauma. Here the water-soluble C60 was prepared and its structural organization has been studied by the atomic force microscopy and dynamic light scattering techniques. The selective biomechanical parameters of muscle soleus contraction and biochemical indicators of blood in rats were evaluated after intramuscular injection of C60 1 h before the muscle trauma initiation. Analysis of the force muscle response after C60 injection (1 mg kg-1 dose) showed its protective effect against ischemia and mechanical injury at the level of 30 ± 2 % and 17 ± 1 %, accordingly, relative to the pathology group. Analysis of biomechanical parameters that are responsible for correcting precise positioning confirmed the effectiveness of C60 at a level of more than 50 ± 3 % relative to the pathology group. Moreover, a decrease in the biochemical indicators of blood by about 33 ± 2 % and 10 ± 1 % in ischemia and mechanical injury, correspondingly, relative to the pathology group occurs. The results obtained demonstrate the ability of C60 to correct the functional activity of damaged skeletal muscle.

Anaemia at mid-pregnancy is associated with prehypertension in late pregnancy among urban women.

Background: Antenatal iron deficiency and anaemia are associated with gestational hypertension and diabetes mellitus, but so are elevated iron stores and haemoglobin. In South Africa, pregnant women receive routine iron supplementation regardless of iron status. Aim: This study aimed to assess associations of antenatal iron status and anaemia with blood pressure in pregnant women in urban South Africa. Secondary to this, associations with heart rate, fasting glucose and glucose tolerance were also investigated. Setting: Johannesburg, South Africa. Methods: A total of 250 pregnant women, aged 27 (24-32) years, were recruited using consecutive sampling. The authors measured biomarkers of iron status and anaemia at < 18 and ± 22 weeks', blood pressure and heart rate at ± 36 weeks', and fasting glucose and glucose tolerance between 24 and 28 weeks' gestation. Associations were determined using multivariable regression models adjusted for confounders. Results: The odds of prehypertension in late pregnancy among women with anaemia at ± 22 weeks' gestation were three times higher than among women without anaemia (odds ratio [OR]: 3.01, 95% confidence interval [CI]: 1.22, 7.42). Participants with anaemia at ± 22 weeks' gestation had 2.15 times higher odds of having elevated mean arterial pressure than women without anaemia (OR: 2.15, 95% CI: 1.01, 4.60). Conclusion: Anaemia at mid-pregnancy could be a predictor of hypertensive disorders in pregnancy. The cause of antenatal anaemia may need further investigation apart from iron deficiency. The effective management of anaemia in pregnant women living in urban South Africa remains a challenge. Contribution: This study provides evidence about the health impact of pregnant women regarding antenatal supplementation practices in South Africa.