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Journal of Biomedical Physics &... Aug 2023Dementia involves a neuronal loss in the primary somatosensory cortex of the parietal lobe, causing dementia patients to perceive pain stimuli hardly. The function of...
BACKGROUND
Dementia involves a neuronal loss in the primary somatosensory cortex of the parietal lobe, causing dementia patients to perceive pain stimuli hardly. The function of temperature sensation declines. Studies measuring brain blood volume using near-infrared light have reported that patients suffering from dementia have less activation than healthy elderly people. However, the majority of these studies used tests related to cognitive function and the frontal lobe, and few have examined thermal sensation.
OBJECTIVE
The present study aimed to investigate the effect of cold and warm stimulation on cerebral blood volume in elderly and young subjects.
MATERIAL AND METHODS
This observational study measured changes in oxygenated hemoglobin concentrations in the frontal cortex during cold and warm stimulation in elderly and young subjects using a near-infrared light device. The mean and standard deviation of the change in oxygenated hemoglobin concentration before and after cold and warm stimulation, as well as the center-of-gravity values, were compared between the young and the elderly.
RESULTS
During warm stimulation, the younger subjects showed an increase in blood oxygenated hemoglobin levels; however, the difference was not significant. For the elderly, no change was observed during the task. The center of gravity values was lower in the young compared to the elderly which was similar to the reaction threshold. No significant changes were observed during cold stimulation.
CONCLUSION
Thermal sensation thresholds were impaired in the elderly compared to the young; however, cerebral blood volume changes were unclear.
PubMed: 37609507
DOI: 10.31661/jbpe.v0i0.2110-1417 -
Animals : An Open Access Journal From... Aug 2023Hematological analysis is commonly used to assess the physiological state of fish. It includes red blood cell parameters, white blood cell parameters, and the number of... (Review)
Review
Hematological analysis is commonly used to assess the physiological state of fish. It includes red blood cell parameters, white blood cell parameters, and the number of thrombocytes per blood volume unit. Hematological analysis is one of the basic tools (often accompanied by biochemical and histopathological analyses) to assess the influence of organic and inorganic substances on fish. It is, therefore, applicable in both ecotoxicology and pharmacotoxicology. The advantages of this research method are the lack of need for specialized laboratory equipment and low costs, and the limitations are the need for extensive experience among the personnel performing the tests. One of the recommended methods of supplementing routinely determined hematological parameters is assessing the cellular composition and activity of hematopoietic tissue. As there is very little scientific data available on the issue of the effects of xenobiotics on the cellular structure of fish head kidney hematopoietic tissue, filling this gap should be considered an urgent need. Therefore, we recommend conducting research with the simultaneous use of hematological and hematopoietic analysis as reliable and complementary methods of assessing the impact of toxic substances on fish.
PubMed: 37627416
DOI: 10.3390/ani13162625 -
Diagnostics (Basel, Switzerland) Jun 2023This article describes the technical principles and clinical applications of dual-energy computed tomography (DECT) in the context of cardiothoracic imaging with a focus... (Review)
Review
This article describes the technical principles and clinical applications of dual-energy computed tomography (DECT) in the context of cardiothoracic imaging with a focus on current developments and techniques. Since the introduction of DECT, different vendors developed distinct hard and software approaches for generating multi-energy datasets and multiple DECT applications that were developed and clinically investigated for different fields of interest. Benefits for various clinical settings, such as oncology, trauma and emergency radiology, as well as musculoskeletal and cardiovascular imaging, were recently reported in the literature. State-of-the-art applications, such as virtual monoenergetic imaging (VMI), material decomposition, perfused blood volume imaging, virtual non-contrast imaging (VNC), plaque removal, and virtual non-calcium (VNCa) imaging, can significantly improve cardiothoracic CT image workflows and have a high potential for improvement of diagnostic accuracy and patient safety.
PubMed: 37371011
DOI: 10.3390/diagnostics13122116 -
Alzheimer's Research & Therapy Apr 2024Although blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known...
BACKGROUND
Although blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known about how these biomarkers predict future brain atrophy and cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer's disease (AD) pathology (amyloid-β [Aβ], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Additionally, we determined whether sex, APOEε4 status, and plasma amyloid-β status modified these associations.
METHODS
Plasma biomarkers were measured using Quanterix SIMOA assays. Regional brain volumes were measured by 3T MRI, and a battery of neuropsychological tests assessed five cognitive domains. Linear mixed effects models adjusted for demographic factors, kidney function, and intracranial volume (MRI analyses) were completed to relate baseline plasma biomarkers to baseline and longitudinal brain volume and cognitive performance.
RESULTS
Brain volume analyses included 622 participants (mean age ± SD: 70.9 ± 10.2) with an average of 3.3 MRI scans over 4.7 years. Cognitive performance analyses included 674 participants (mean age ± SD: 71.2 ± 10.0) with an average of 3.9 cognitive assessments over 5.7 years. Higher baseline pTau-181 was associated with steeper declines in total gray matter volume and steeper regional declines in several medial temporal regions, whereas higher baseline GFAP was associated with greater longitudinal increases in ventricular volume. Baseline Aβ and NfL levels were not associated with changes in brain volume. Lower baseline Aβ (higher Aβ burden) was associated with a faster decline in verbal memory and visuospatial performance, whereas higher baseline GFAP was associated with a faster decline in verbal fluency. Results were generally consistent across sex and APOEε4 status. However, the associations of higher pTau-181 with increasing ventricular volume and memory declines were significantly stronger among individuals with higher Aβ burden, as was the association of higher GFAP with memory decline.
CONCLUSIONS
Among cognitively unimpaired older adults, plasma biomarkers of AD pathology (pTau-181) and astrogliosis (GFAP), but not neuronal injury (NfL), serve as markers of future brain atrophy and cognitive decline.
Topics: Humans; Female; Male; Biomarkers; Aged; Atrophy; Brain; Alzheimer Disease; Amyloid beta-Peptides; Cognitive Dysfunction; tau Proteins; Longitudinal Studies; Glial Fibrillary Acidic Protein; Middle Aged; Aged, 80 and over; Neurofilament Proteins; Neurodegenerative Diseases; Neuropsychological Tests; Magnetic Resonance Imaging; Peptide Fragments
PubMed: 38689358
DOI: 10.1186/s13195-024-01459-y -
Pflugers Archiv : European Journal of... May 2024In this review, we will cover (i) the proteolytic cascade of the RAAS, (ii) its regulation by multiple feedback-controlled parameters, and (iii) the major effects of the... (Review)
Review
In this review, we will cover (i) the proteolytic cascade of the RAAS, (ii) its regulation by multiple feedback-controlled parameters, and (iii) the major effects of the RAAS. For the effects of the RAAS, we focus on the role of the RAAS in the regulation of volume homeostasis and vascular tone, as major determinants of arterial blood pressure.
Topics: Renin-Angiotensin System; Humans; Animals; Blood Pressure; Aldosterone
PubMed: 38233636
DOI: 10.1007/s00424-024-02908-1 -
Critical Care (London, England) Feb 2024Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery.
METHODS
In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate.
RESULTS
The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure.
CONCLUSION
The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.
Topics: Humans; Albumins; Blood Volume; Hemodynamics; Hemorrhage; Hypovolemia; Isotonic Solutions; Ringer's Lactate; Ringer's Solution
PubMed: 38317178
DOI: 10.1186/s13054-024-04821-6 -
Acta Biomaterialia Sep 2023Immunotherapy has revolutionized the treatment of dozens of cancers and became a standard of care for some tumor types. However, the majority of patients do not benefit...
Immunotherapy has revolutionized the treatment of dozens of cancers and became a standard of care for some tumor types. However, the majority of patients do not benefit from current immunotherapeutics and many develop severe toxicities. Therefore, the identification of biomarkers to classify patients as likely responders or non-responders to immunotherapy is a timely task. Here, we test ultrasound imaging markers of tumor stiffness and perfusion. Ultrasound imaging is non-invasive and clinically available and can be used both for stiffness and perfusion evaluation. In this study, we employed syngeneic orthotopic models of two breast cancers, a fibrosarcoma and a melanoma, to demonstrate that ultrasound-derived measures of tumor stiffness and perfusion (i.e., blood volume) correlate with the efficacy of immune checkpoint inhibition (ICI) in terms of changes in primary tumor volume. To modulate tumor stiffness and perfusion and thus, get a range of therapeutic outcomes, we employed the mechanotherapeutic tranilast. Mechanotherapeutics combined with ICI are advancing through clinical trials, but biomarkers of response have not been tested until now. We found the existence of linear correlations between tumor stiffness and perfusion imaging biomarkers as well as strong linear correlations between the stiffness and perfusion markers with ICI efficacy on primary tumor growth rates. Our findings set the basis for ultrasound biomarkers predictive of ICI therapy in combination with mechanotherapeutics. STATEMENT OF SIGNIFICANCE: Hypothesis: Monitoring Tumor Microenvironment (TME) mechanical abnormalities can predict the efficacy of immune checkpoint inhibition and provide biomarkers predictive of response. Tumor stiffening and solid stress elevation are hallmarks of tumor patho-physiology in desmoplastic tumors. They induce hypo-perfusion and hypoxia by compressing tumor vessels, posing major barriers to immunotherapy. Mechanotherapeutics is a new class of drugs that target the TME to reduce stiffness and improve perfusion and oxygenation. In this study, we show that measures of stiffness and perfusion derived from ultrasound shear wave elastography and contrast enhanced ultrasound can provide biomarkers of tumor response.
Topics: Humans; Immune Checkpoint Inhibitors; Tumor Burden; Melanoma; Biomarkers; Elasticity Imaging Techniques; Immunotherapy; Perfusion; Tumor Microenvironment
PubMed: 37321529
DOI: 10.1016/j.actbio.2023.06.007 -
Regulation of the renin-angiotensin-aldosterone system by cyclic nucleotides and phosphodiesterases.Frontiers in Endocrinology 2023The renin-angiotensin-aldosterone system (RAAS) is one of the key players in the regulation of blood volume and blood pressure. Dysfunction of this system is connected... (Review)
Review
The renin-angiotensin-aldosterone system (RAAS) is one of the key players in the regulation of blood volume and blood pressure. Dysfunction of this system is connected with cardiovascular and renal diseases. Regulation of RAAS is under the control of multiple intracellular mechanisms. Cyclic nucleotides and phosphodiesterases are the major regulators of this system since they control expression and activity of renin and aldosterone. In this review, we summarize known mechanisms by which cyclic nucleotides and phosphodiesterases regulate renin gene expression, secretion of renin granules from juxtaglomerular cells and aldosterone production from cells of adrenal gland. We also discuss several open questions which deserve future attention.
Topics: Renin-Angiotensin System; Renin; Aldosterone; Nucleotides, Cyclic; Phosphoric Diester Hydrolases
PubMed: 37674612
DOI: 10.3389/fendo.2023.1239492 -
Blood Transfusion = Trasfusione Del... Nov 2023Most public cord blood (CB) banks currently discard more than 80% of umbilical CB units not suitable for hemopoietic stem cell transplant due to low stem cell count....
BACKGROUND
Most public cord blood (CB) banks currently discard more than 80% of umbilical CB units not suitable for hemopoietic stem cell transplant due to low stem cell count. Although CB platelets, plasma, and red blood cells have been used for experimental allogeneic applications in wound healing, corneal ulcer treatment, and neonatal transfusion, no standard procedures for their preparation have been defined internationally.
MATERIALS AND METHODS
A network of 12 public CB banks in Spain, Italy, Greece, the UK, and Singapore developed a protocol to validate a procedure for the routine production of CB platelet concentrate (CB-PC), CB platelet-poor plasma (CB-PPP), and CB leukoreduced red blood cells (CB-LR-RBC) using locally available equipment and the commercial BioNest ABC and EF medical devices. CB units with >50 mL volume (excluding anticoagulant) and ≥150×10/L platelets were double centrifuged to obtain CB-PC, CB-PPP, and CB-RBC. The CB-RBC were diluted with saline-adenine-glucose-mannitol (SAGM), leukoreduced by filtration, stored at 2-6°C, and tested for hemolysis and potassium (K+) release over 15 days, with gamma irradiation performed on day 14. A set of acceptance criteria was pre-defined. This was for CB-PC: volume ≥5 mL and platelet count 800-1,200×10/L; for CB-PPP: platelet count <50×10/L; and for CB-LR-RBC: volume ≥20 mL, hematocrit 55-65%, residual leukocytes <0.2×10/unit, and hemolysis ≤0.8%.
RESULTS
Eight CB banks completed the validation exercise. Compliance with acceptance criteria was 99% for minimum volume and 86.1% for platelet count in CB-PC, and 90% for platelet count in CB-PPP. Compliance in CB-LR-RBC was 85.7% for minimum volume, 98.9% for residual leukocytes, and 90% for hematocrit. Compliance for hemolysis ≤0.8% decreased from 89.0 to 63.2% from day 0 to 15. K+ release increased from 3.0±1.8 to 25.0±7.0 mmol/L from day 0 to 15, respectively.
DISCUSSION
The MultiCord12 protocol was a useful tool to develop preliminary standardization of CB-PC, CB-PPP, and CB-LR-RBC.
Topics: Infant, Newborn; Humans; Hemolysis; Blood Banking; Erythrocytes; Blood Banks; Blood Platelets
PubMed: 37146297
DOI: 10.2450/BloodTransfus.492 -
Molecular Cancer Nov 2023The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole...
The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Neoplastic Cells, Circulating; Liquid Biopsy; Biomarkers, Tumor; Blood Volume
PubMed: 37957606
DOI: 10.1186/s12943-023-01880-1