Total Hemoglobin Concentration Research Articles

#337 Renal 3D photoacoustic imaging and contrast-enhanced ultrasound to assess oxygenation and perfusion and to predict fibrosis after ischemia-reperfusion

Abstract Background and Aims Renal 3D photo-acoustic imaging (3D-PAI) and contrast-enhanced ultrasound (CEUS) are promising tools in mice models to assess repeatedly and non-invasively renal ischemia-reperfusion (RIR) consequences and damages, or their improvement by nephroprotective strategies like mild therapeutic hypothermia (mTH), at the early phase of reperfusion as well as in the chronic late phase. Method C57Bl6 mice underwent 15 minutes of unilateral renal vascular clamping, with body temperature at 37°C (RIR-37°C, n=7) or mTH at 34°C (RIR-34°C, n=7), or a sham procedure (Sham, n=5). Renal volume and oxygen saturation (sO2-3D; corresponding to the percentage of oxyhemoglobin over the total hemoglobin content) were measured with 3D-PAI (3D reconstruction of the whole kidney through multi-plane acquisition with an automatized mobile support), and renal perfusion parameters (rBV, mTT, rBF) with CEUS (“destruction-replenishment” model of intravenous microbubbles), performed with VEVO3100 echograph (Fujifilm Visualsonic) 1 week before RIR (basal), 20 minutes after reperfusion, and 1 month after. Renal fibrosis was quantified at 1 month with Masson's trichrome coloration on histological samples. Data were compared with Mann-Whitney test or Wilcoxon test (paired data) as appropriate. Correlation was tested by Spearman test. All animal procedures were approved by the Ethics Committee. Results Sham showed no significant changes during follow-up. RIR-37°C led to renal hypotrophy (volume on 3D-PAI) and fibrosis at 1 month, compared to RIR-34°C (median volume 76 IQR [71-119] vs 143 IQR[108-180] mm3; p=0.03), and those parameters were correlated (R=−0.49; p=0.03). In RIR-37°C, sO2-3D tended to lower at 20 minutes compared to basal values (median sO2-3D 37 IQR [37-44] vs 49 IQR [36-57]%; p=0.08), but not in RIR-34°C (p > 0.99), and these early variations of sO2-3D were correlated with fibrosis at 1 month (R=−0.48; p=0.04). Renal perfusion was altered in RIR-37°C at 20 minutes compared to basal values (median rBV 73 IQR [46-105] vs 100 IQR [89-126] a.u.; p=0.047), and remained altered at 1 month (median rBV 71 IQR [57-83] a.u.; p=0.03), but not in RIR-34°C (p=0.47 at both 20 minutes and 1 month). Renal perfusion early alterations at 20 minutes were correlated with late alterations at 1 month (R=0.63; p=0.005), and tended to correlate with fibrosis (R=−0.41; p=0.08). Conclusion Renal 3D-PAI (on the whole 3D-reconstructed kidney) and CEUS can detect early alterations of renal perfusion and oxygen saturation after RIR, and predict chronic disturbances of perfusion and the onset of fibrosis, as well as the protection conferred by mTH. 3D-PAI can also be used to evaluate non-invasively renal volume as a surrogate of renal fibrosis after RIR.

#658 Analysis of cerebral blood volume and flow changes in ESRD patients undergoing hemodialysis using functional near-infrared spectroscopy

Abstract Background and Aims End stage renal disease (ESRD) patients undergoing hemodialysis experience diverse neurological complications. However, studies regarding how hemodialysis is related to these neurological problems are limited. This study investigated cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. Method ESRD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 – HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. Results Thirty hemodialysis patients were analyzed. Between the Pre-HD and Post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p=0.046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p=0.029). Additionally, between Pre-HD and Post-HD periods, HbD tended to increase; however, this was not statistically significant (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p=0.094). Conclusion We demonstrated that during one hemodialysis session, the relative change in CBV increased post-HD compared with pre-HD. These results are expected to help understand the mechanisms underlying the effects of hemodialysis on brain function.

Hemoglobin concentration and blood shift during dry static apnea in elite breath hold divers.

Elite breath-hold divers (BHD) enduring apneas of more than 5min are characterized by tolerance to arterial blood oxygen levels of 4.3kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD (n = 11) and matched controls (n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD. After 4min of apnea, left ventricular myocardial mass (LVMM) determined by 15O-H2O-PET/CT (n = 6) and cardiac MRI (n = 6), was unaltered compared to rest. During maximum apnea (∼6min), lower extremity volume assessed by DXA-scan revealed a ∼268mL decrease, and spleen volume, assessed by ultrasonography, decreased ∼102mL. Compared to age, BMI and VO2max matched controls (n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations. Our results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans.

Detection of Asymptomatic Sickle Cell Hemoglobin Carriers and Fetal Hemoglobin Regulating Genetic Variants in African Descendants from Oaxaca, Mexico.

Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the β-globin mutation detection assay (β-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.

Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia

BackgroundExagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing of the erythroid-specific enhancer region of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs).MethodsWe conducted an open-label, single-group, phase 3 study of exa-cel in patients 12 to 35 years of age with transfusion-dependent β-thalassemia and a β0/β0, β0/β0-like, or non–β0/β0-like genotype. CD34+ HSPCs were edited by means of CRISPR-Cas9 with a guide mRNA. Before the exa-cel infusion, patients underwent myeloablative conditioning with pharmacokinetically dose-adjusted busulfan. The primary end point was transfusion independence, defined as a weighted average hemoglobin level of 9 g per deciliter or higher without red-cell transfusion for at least 12 consecutive months. Total and fetal hemoglobin concentrations and safety were also assessed.ResultsA total of 52 patients with transfusion-dependent β-thalassemia received exa-cel and were included in this prespecified interim analysis; the median follow-up was 20.4 months (range, 2.1 to 48.1). Neutrophils and platelets engrafted in each patient. Among the 35 patients with sufficient follow-up data for evaluation, transfusion independence occurred in 32 (91%; 95% confidence interval, 77 to 98; P<0.001 against the null hypothesis of a 50% response). During transfusion independence, the mean total hemoglobin level was 13.1 g per deciliter and the mean fetal hemoglobin level was 11.9 g per deciliter, and fetal hemoglobin had a pancellular distribution (≥94% of red cells). The safety profile of exa-cel was generally consistent with that of myeloablative busulfan conditioning and autologous HSPC transplantation. No deaths or cancers occurred.ConclusionsTreatment with exa-cel, preceded by myeloablation, resulted in transfusion independence in 91% of patients with transfusion-dependent β-thalassemia. (Supported by Vertex Pharmaceuticals and CRISPR Therapeutics; CLIMB THAL-111 ClinicalTrials.gov number, NCT03655678.)

In vivo assessment of bladder cancer with diffuse reflectance and fluorescence spectroscopy: A comparative study.

The aim of this work is to assess the performance of multimodal spectroscopic approach combined with single core optical fiber for detection of bladder cancer during surgery in vivo. Multimodal approach combines diffuse reflectance spectroscopy (DRS), fluorescence spectroscopy in the visible (405 nm excitation) and near-infrared (NIR) (690 nm excitation) ranges, and high-wavenumber Raman spectroscopy. All four spectroscopic methods were combined in a single setup. For 21 patients with suspected bladder cancer or during control cystoscopy optical spectra of bladder cancer, healthy bladder wall tissue and/or scars were measured. Classification of cancerous and healthy bladder tissue was performed using machine learning methods. Statistically significant differences in relative total haemoglobin content, oxygenation, scattering, and visible fluorescence intensity were found between tumor and normal tissues. The combination of DRS and visible fluorescence spectroscopy allowed detecting cancerous tissue with sensitivity and specificity of 78% and 91%, respectively. The addition of features extracted from NIR fluorescence and Raman spectra did not improve the quality of classification. This study demonstrates that multimodal spectroscopic approach allows increasing sensitivity and specificity of bladder cancer detection in vivo. The developed approach does not require special probes and can be used with single-core optical fibers applied for laser surgery.

Maximizing the Reliability and Precision of Measures of Prefrontal Cortical Oxygenation Using Frequency-Domain Near-Infrared Spectroscopy.

Frequency-domain near-infrared spectroscopy (FD-NIRS) has been used for non-invasive assessment of cortical oxygenation since the late 1990s. However, there is limited research demonstrating clinical validity and general reproducibility. To address this limitation, recording duration for adequate validity and within- and between-day reproducibility of prefrontal cortical oxygenation was evaluated. To assess validity, a reverse analysis of 10-min-long measurements (n = 52) at different recording durations (1-10-min) was quantified via coefficients of variation and Bland-Altman plots. To assess within- and between-day within-subject reproducibility, participants (n = 15) completed 2-min measurements twice a day (morning/afternoon) for five consecutive days. While 1-min recordings demonstrated sufficient validity for the assessment of oxygen saturation (StO2) and total hemoglobin concentration (THb), recordings ≥4 min revealed greater clinical utility for oxy- (HbO) and deoxyhemoglobin (HHb) concentration. Females had lower StO2, THb, HbO, and HHb values than males, but variability was approximately equal between sexes. Intraclass correlation coefficients ranged from 0.50-0.96. The minimal detectable change for StO2 was 1.15% (95% CI: 0.336-1.96%) and 3.12 µM for THb (95% CI: 0.915-5.33 µM) for females and 2.75% (95%CI: 0.807-4.70%) for StO2 and 5.51 µM (95%CI: 1.62-9.42 µM) for THb in males. Overall, FD-NIRS demonstrated good levels of between-day reliability. These findings support the application of FD-NIRS in field-based settings and indicate a recording duration of 1 min allows for valid measures; however, data recordings of ≥4 min are recommended when feasible.

Assessment of patho-physiological responses, gill histopathology and SEM analysis in common carp (Cyprinus carpio) exposed to varied doses of chloramine-T: A potent chemotherapeutic agent

Chloramine-T (Cl-T) is a chemo-therapeutant used at aquafarms to control fish mortalities associated with bacterial and parasitic infections in freshwater aquaculture. It is also effective as a disinfectant against a wide range of viruses known to cause disease in fish. However, a very little information is available on the patho-physiological alterations in common carp (Cyprinus carpio) exposed to different doses of Cl-T. Herein, the present study aimed to assess the patho-physiological changes in common carp exposed to different doses of Cl-T (20 mg/L, 100 mg/L, and 200 mg/L) for 15 days followed by a post-exposure assessment for another 15 days. The results indicated a significant decrease in haematological indices viz., Total Erythrocyte Count (TEC), Total Leucocyte Count (TLC), Total Platelet Count (TPC), Haemoglobin (Hb), Haematocrit (Hct), and Mean Corpuscular Haemoglobin Concentration (MCHC) at higher Cl-T concentrations. Whereas, a decrease in some of the immune-biochemical parameters was also noted viz., lysozyme, NBT, Total Ig, phagocytic activity, protein, albumin and globulin in a dose-dependent manner. However, a significant increase in Mean Corpuscular Volume (MCV) and glucose levels was observed during exposure period. Histopathological analysis revealed gill hypertrophy, fusion of secondary lamellae, sloughing of lamellar epithelium and gill necrosis which were more pronounced with increasing concentration of Cl-T. The maximum damage to the gill was noted at a concentration of 200 mg/L. Whereas, scanning electron microscopic (SEM) analysis of gill revealed sloughing of lamellar epithelium, reduced interlamellar space and hypertrophy of secondary lamellae in Cl-T exposed fishes. Together, these results suggest that Cl-T exposure in common carp at 20 mg/L has a mild and acceptable effect on gill and physiology of fish, 100 mg/L has moderate effect, and 200 mg/L causes extensive damage to gills and physiology of fish.

Local alternating heat and cold stimulation affects hemodynamics and oxygenation in fatigued muscle tissue and autonomic nervous activity: a single-arm interventional study

BackgroundLocal alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping effect and consequently promoting increased tissue blood flow and oxygenation. This study aimed to examine the effects of local alternating heat and cold stimulation, using a wearable thermal device, on the hemodynamics of fatigued muscle tissue and autonomic nervous activity.MethodsTwenty healthy individuals experienced fatigue in the periarticular muscles of the shoulder joint due to a typing task. Local alternating heat and cold stimulations were then applied to the upper trapezius muscle. Muscle hardness was measured using a muscle hardness meter, and muscle tissue hemodynamics and oxygenation were evaluated using near-infrared spectroscopy before and after the stimulation. Autonomic nervous activity was also evaluated using heart rate variability.ResultsAlternating heat and cold stimulation decreased muscle hardness of the fatigued trapezius muscle from 1.38 ± 0.15 to 1.31 ± 0.14 N (P < 0.01). The concentration of total hemoglobin in the trapezius muscle tissue increased from − 0.21 ± 1.36 to 2.29 ± 3.42 µmol/l (P < 0.01), and the tissue hemoglobin oxygen saturation also increased from 70.1 ± 5.4 to 71.1 ± 6.0% (P < 0.05). Additionally, the heart rate variability parameter, which is an index of sympathetic nervous activity, increased from 3.82 ± 2.96 to 6.86 ± 3.49 (P < 0.01). A correlation was found between increased tissue hemoglobin oxygen saturation and increased parameters of sympathetic nervous activity (r = 0.50, P < 0.05).ConclusionsLocal alternating heat and cold stimulation affected the hemodynamic response in fatigued muscle tissue and autonomic nervous activity. This stimulation is more efficient than conventional contrast baths in terms of mobility and temperature control and has potential as a new versatile therapeutic intervention for muscle fatigue.Trial registrationUMIN-CTR (UMIN000040087: registered on April 7, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045710. UMIN000040620: registered on June 1, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359).

Can diffuse reflectance spectroscopy identify shuntodynia in pediatric hydrocephalus patients?

Shuntodynia is patient reported pain at the site of the implanted ventriculoperitoneal (VP) shunt. Pediatric hydrocephalus requiring shunt placement is a chronic and prevalent standard of care treatment and requires lifetime management. Shuntodynia is a subjective measure of shunt dysfunction. Quantitative, white-light tissue spectroscopy could be used to objectively identify this condition in the clinic. Pediatric subjects were recruited for optical sensing during routine clinical follow-up visits, post-VP shunt implantations. Acquired optical signals were translated into skin-hemodynamic signatures and were compared between subjects that reported shuntodynia versus those that did not. Diffuse reflectance spectroscopy (DRS) measurements were collected between 450 and 700nm using a single-channel fiber-optical probe from () patients. Multiple reflectance spectra were obtained by the attending physician from regions both proximal and distal to the VP shunt sites and from a matched contralateral site for each subject. Acquired reflectance spectra were processed quantitatively into functional tissue optical endpoints. A two-way, repeated measures analysis of variance was used to assess whether and which of the optical variables were statistically separable, across subjects with shuntodynia versus those without. Analyses indicated that intrapatient differences in vascular oxygen saturation measured between shunt sites relative to that obtained at the scar or contralateral sites was significantly lower in the pain group. We also find that the total hemoglobin concentrations at the shunt site were lowest relative to the other sites for subjects reporting pain. These findings suggest that shuntodynia pain arises in the scalp tissue around the implanted shunts and may be caused due to hypoxia and inflammation. Optically derived hemodynamic variables were statistically significantly different in subjects presenting with shuntodynia relative to those without. DRS could provide a viable mode in routine bedside monitoring of subjects with VP shunts for clinical management and assessment of shuntodynia.

Quantitative Analysis of Shear Wave Elastography and US-Guided Diffuse Optical Tomography for Evaluating Biological Characteristics of Breast Cancer

Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer. A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (Emax), Mean Elasticity (Emean), Standard Deviation of Elasticity (Esd), and Area Ratiowere measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics. Lesions in patient groups with ER-, PR-, HER2+, high Ki67, LVI+, and ALN+exhibited higher THC, Emax, and Esd compared to groups with ER+, PR+, HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with Smax (r=0.340, P<0.001), Emax (r=0.339, P<0.001), Emean (r=0.201, P=0.003), and Esd (r=0.313, P<0.001). US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with Emax, Emean, and Esd.

HAEMATO-BIOCHEMCIAL STUDIES OF NANOPARTICLE-BASED VACCINE AGAINST R2B STRAIN OF NEW CASTLE DISEASE IN CHICKS

HAEMATO-BIOCHEMCIAL STUDIES OF NANOPARTICLE-BASED VACCINE AGAINST R2B STRAIN OF NEW CASTLE DISEASE IN CHICKS

In vivo visualization of burn depth in skin tissue of rats using hemoglobin parameters estimated by diffuse reflectance spectral imaging.

Burn injuries represent a global public health problem that kills an estimated 180,000 people annually. Non-fatal burns result in prolonged hospitalization, disfigurement, and disability. The most common, convenient, and widely used method for assessing burn depth is physical or visual examination, but the accuracy of this method is reportedly poor (60% to 75%). Rapid, correct assessment of burn depth is very important for the optimal management and treatment of burn patients. New methods of burn depth assessment that are inexpensive, simple, rapid, non-contact, and non-invasive are therefore needed. The aim of this study was to propose an approach to visualize the spatial distribution of burn depth using hemoglobin parameters estimated from spectral diffuse reflectance imaging and to demonstrate the feasibility of the proposed approach for differentiating burn depth in a rat model of scald burn injury. The new approach to creating a spatial map of burn depth was based on canonical discriminant analysis (CDA) of total hemoglobin concentration, tissue oxygen saturation, and methemoglobin saturation as estimated from spectral diffuse reflectance images. Burns of three different degrees of severity were created in rat dorsal skin by 10-s exposure to water maintained at 70°C, 78°C, and 98°C, respectively. Spectral images for dorsal regions were acquired under anesthesia immediately after burn injury and at 24h, 48h, and 72h after injury. Most areas of images in the group with skin exposed to 70°C water and 98°C water were classified as 70°C burn and 98°C burn, respectively. In contrast, no significant difference between areas classified as 78°C burn and 98°C burn from 24h to 72h was evident in the group with skin exposed to 78°C water, suggesting that burn depth was heterogeneous. The proposed approach combining diffuse reflectance spectral imaging and CDA appears promising for differentiating 70°C burns from 78°C burns and 98°C burns, and 98°C burns from 70°C burns and 78°C burns at 24 to 72h after burn injury in a rat model of scald burn injury.

Arterial blood gas measurements are different for brachycephalic and nonbrachycephalic dogs acclimatized to an altitude of 1,535 meters.

To define reference intervals (RIs) for arterial blood gas (aBG) measurements in healthy, nonsedated, dolichocephalic, and mesocephalic (nonbrachycephalic) dogs at approximately 1,535 m above sea level and compare these findings with healthy, nonsedated, brachycephalic dogs living at the same altitude. 120 adult nonbrachycephalic dogs and 20 adult brachycephalic dogs. Cases were prospectively enrolled from October 2021 to June 2022. Dogs were enrolled from the community or after presentation for wellness examinations or minor injuries including lacerations, nail injuries, and lameness. Physical examinations and systolic blood pressure (sBP) measurements were obtained before blood sample collection. Arterial blood was collected from the dorsal pedal artery or femoral artery. After data collection, brachycephalic dogs underwent pre- and postexercise tolerance assessments. The mean and RI values for arterial pH (7.442; 7.375 to 7.515), partial pressure of oxygen in arterial blood (Pao2; 78.3; 59.2 to 92.7 mm Hg), partial pressure of carbon dioxide in arterial blood (Paco2; 28.0; 21.5 to 34.4 mm Hg), saturation of arterial oxygen (Sao2; 98.4; 84.3% to 101.4%), HCO3 (18.9; 14.9 to 22.4 mmol/L), concentration of total hemoglobin (ctHb; 17.5; 13.4 to 21.1 g/dL), and sBP (133; 94 to 180 mm Hg) were established for healthy nonbrachycephalic dogs at 1,535-m altitude. All aBG measurements were statistically and clinically different from those previously reported for dogs at sea level. Brachycephalic dogs had significantly lower Pao2 and Sao2 (P = .0150 and P = .0237, respectively) and significantly higher ctHb (P = .0396) compared to nonbrachycephalic dogs acclimatized to the same altitude; the nonbrachycephalic RIs were not transferable to the brachycephalic dogs for Pao2. This study represents the first collation of aBG measurements for healthy nonbrachycephalic dogs acclimatized to an altitude of 1,535 m. Additionally, this study identified differences in arterial oxygenation measurements between brachycephalic and nonbrachycephalic dogs. RIs in brachycephalic dogs need to be established.

Motion-resistant three-wavelength spatial frequency domain imaging system with ambient light suppression using an 8-tap CMOS image sensor.

We present a motion-resistant three-wavelength spatial frequency domain imaging (SFDI) system with ambient light suppression using an 8-tap complementary metal-oxide semiconductor (CMOS) image sensor (CIS) developed at Shizuoka University. The system addresses limitations in conventional SFDI systems, enabling reliable measurements in challenging imaging scenarios that are closer to real-world conditions. Our study demonstrates a three-wavelength SFDI system based on an 8-tap CIS. We demonstrate and evaluate the system's capability of mitigating motion artifacts and ambient light bias through tissue phantom reflectance experiments and in vivo volar forearm experiments. We incorporated the Hilbert transform to reduce the required number of projected patterns per wavelength from three to two per spatial frequency. The 8-tap image sensor has eight charge storage diodes per pixel; therefore, simultaneous image acquisition of eight images based on multi-exposure is possible. Taking advantage of this feature, the sensor simultaneously acquires images for planar illumination, sinusoidal pattern projection at three wavelengths, and ambient light. The ambient light bias is eliminated by subtracting the ambient light image from the others. Motion artifacts are suppressed by reducing the exposure and projection time for each pattern while maintaining sufficient signal levels by repeating the exposure. The system is compared to a conventional SFDI system in tissue phantom experiments and then in vivo measurements of human volar forearms. The 8-tap image sensor-based SFDI system achieved an acquisition rate of 9.4 frame sets per second, with three repeated exposures during each accumulation period. The diffuse reflectance maps of three different tissue phantoms using the conventional SFDI system and the 8-tap image sensor-based SFDI system showed good agreement except for high scattering phantoms. For the in vivo volar forearm measurements, our system successfully measured total hemoglobin concentration, tissue oxygen saturation, and reduced scattering coefficient maps of the subject during motion (16.5cm/s) and under ambient light (28.9lx), exhibiting fewer motion artifacts compared with the conventional SFDI. We demonstrated the potential for motion-resistant three-wavelength SFDI system with ambient light suppression using an 8-tap CIS.

Differential impact of heat and hypoxia on dynamic oxygen uptake and deoxyhemoglobin parameters during incremental exhaustive exercise.

Purpose: This study aims to explore the relationship between the dynamic changes in oxygen uptake () and deoxyhemoglobin (HHb) and peripheral fatigue in athletes during incremental exhaustive exercise under different environmental conditions, including high temperature and humidity environment, hypoxic environment, and normal conditions. Methods: 12 male modern pentathlon athletes were recruited and performed incremental exhaustive exercise in three different environments: normal condition (23°C, 45%RH, FiO2 = 21.0%, CON), high temperature and humidity environment (35°C, 70%RH, FiO2 = 21.0%, HOT), and hypoxic environment (23°C, 45%RH, FiO2 = 15.6%, HYP). Gas metabolism data of the athletes were collected, and muscle oxygen saturation (SmO2) and total hemoglobin content in the vastus lateralis muscles (VL) were measured to calculate the deoxyhemoglobin content. Linear and nonlinear function models were used to fit the characteristic parameters of and HHb changes. Results: The results showed that compared to the CON, , , and exercise time were decreased in the HOT and HYP (p < 0.05). and OUES were reduced in the HOT and HYP compared to the CON (p < 0.05). The Gas exchange threshold in the CON corresponded to higher than in the HYP and HOT (p < 0.05). was reduced in the HOT compared to the HYP (p < 0.05). ΔEHHb was higher in the HOT compared to the CON (p < 0.05). ΔEHHb-1 was increased in the HYP compared to the CON (p < 0.05). There was a negative correlation between ΔEHHb and corresponding in the HOT (r = -0.655, p < 0.05), and a negative correlation between ΔEHHb-1 and corresponding in the HYP (r = -0.606, p < 0.05). Conclusion: Incremental exhaustive exercise in hypoxic environment and high temperature and humidity environments inhibits gas exchange and oxygen supply to skeletal muscle tissue in athletes. For athletes, the accelerated deoxygenation response of skeletal muscles during incremental exhaustive exercise in high temperature and humidity environments, as well as the excessive deoxygenation response before BP of deoxyhemoglobin in hypoxic environment, may be contributing factors to peripheral fatigue under different environmental conditions.

Haematological, biochemical, enzymological changes and mitochondrial dysfunction of liver in freshwater climbing perch Anabas testudineus during their acute and chronic exposure to sodium fluoride

Anthropogenic activities are increasing fluoride concentration in watercourses. The present study focuses on the sublethal toxicity of sodium fluoride during sub-chronic and chronic time periods in the freshwater fish Anabas testudineus. The 96-hour LC50 value for fluoride was found to be 616.50 mg/L. Excessive mucous production and hyper excitability, followed by loss of balance, were seen in fish under acute fluoride exposure. Significant reduction in yield and specific growth rate of fish were assessed at 15, 30 and 45-days exposure intervals. Different bio-indicators like Hepatosomatic-index, Gonadosomatic-index and fecundity were reduced significantly in fish exposed to 10% (61.6 mg/L) and 20% (123.2 mg/L) of 96 h of LC50 values of fluoride in comparison to control. Toxicant concentrations directly correlated with parameter lowering. Fluoride exposure increased plasma glucose, creatinine, AST, and ALT and reduced total RBC, haemoglobin content, Hct (%), plasma protein, and cholesterol. Moreover, fluoride exposure significantly reduces the mitochondrial membrane potential in liver. This may result in metabolic depression, haematological, biochemical, and enzymological stress. The in-silico structural analysis predicts that fluoride may impede cytochrome c oxidase of the electron transport system, hence inhibiting mitochondrial functionality. These findings collectively highlight the urgent need for stringent regulation and monitoring of fluoride levels in freshwater ecosystems, as the subchronic and chronic effects observed in A. testudineus may have broader implications for aquatic ecosystems.

Effect of Total Hemoglobin on Glycated Hemoglobin (HbA1c) in Type 2 Diabetes Mellitus

Background: Glycated hemoglobin (HbA1c) is a pivotal marker in the diagnosis, prognosis, and therapeutic monitoring of diabetes mellitus. Given the involvement of hemoglobin in non-enzymatic glycation reactions, it is hypothesized that total hemoglobin concentration might impact HbA1c levels alongside blood glucose concentrations. Objectives: This study aimed to estimate and compare plasma fasting glucose level and total hemoglobin level in type 2 diabetes mellitus (T2DM) patients with and without anemia. The study also aimed to estimate HbA1C and compare with calculated HbA1C using formula in T2DM patients with and without anemia and to correlate between total hemoglobin levels with directly measured HbA1c in T2DM patients with and without anemia. Methodology: This cross-sectional study, employing purposive sampling, investigated 30 anemic and 30 non-anemic Type 2 Diabetes Mellitus (T2DM) patients at the Central Diagnostic Laboratory. Total Hemoglobin, HbA1C, and Fasting Plasma Glucose were measured for the patients and the data was analyzed. Results: Independent 't' tests revealed significant differences (p &lt; 0.0001) in estimated HbA1c, fasting blood sugar, calculated HbA1c, and Hb levels between the two groups. Subgroup analyses exhibited significant differences in estimated HbA1c for both groups individually (p = 0.003 for T2DM without anemia and p&lt;0.0001 for T2DM with anemia). Pearson's correlation analysis indicated no significant correlation between HbA1c and hemoglobin in either subgroup. Similarly linear regression analysis treating HbA1c as the dependent variable yielded a non-significant p-value, suggesting that hemoglobin levels do not significantly influence HbA1c. Conclusion: In conclusion, regardless of anemia status, our findings suggest that hemoglobin is not a significant predictor of HbA1c levels in T2DM patients, offering valuable insights into factors influencing HbA1c variability in diabetic populations.

Use of Lactoferrin Supplement as an Efficient Antioxidant to Ameliorate the Effects of Mercury-induced Oxidative Stress in Male Wistar Rats

Background: The present study was carried out to test the antioxidant activity of lactoferrin as a dietary supplement to alleviate the effects of oxidative stress induced by mercury toxicity. Hematological and biochemical assays were employed to evaluate the ameliorating effects of lactoferrin. Methods: Sixty male Wistar rats were allotted randomly and equally into three groups; animals in Group 1 served as untreated control, animals in Group 2 were administered orally with mercuric chloride (HgCl2) at the dose of 6 mg/kg bw/day, and animals in Group 3 were administered with HgCl2 at the same dose and orally dosed with lactoferrin (400 mg/kg bw/day). Hematological indices (erythrocytic and total leukocytic counts, hemoglobin concentration%, and packed cell volume, (PCV%), and biochemical parameters (serum and homogenates of liver and kidney tissues) were assessed in all animals. Serum and tissue homogenate levels of total thiols, glutathione (GSH), catalase, and total antioxidant capacity (TAC) represented the antioxidant markers. The oxidation markers were represented by H2O2 and malondialdehyde (MDA). Results: Compared to the untreated control group, animals in Group 2 (administered with HgCl2) exhibited significantly increased levels of serum enzymes (alanine transferase (ALT), aspertate transferase (AST), and alkaline phosphatase), urea, blood urea nitrogen, creatinine, H2O2, and MDA. These animals showed significantly decreased levels of erythrocytic and total leukocytic counts, hemoglobin concentration, PCV%, total proteins, total thiols, GSH, catalase, and TAC. The hematological and biochemical changes were comparatively reversed toward the control levels in animals of Group 3 (administered with HgCl2 and orally dosed with lactoferrin). The reversed levels of hematological and biochemical parameters were significantly different compared to Group 2. Conclusions: Based on the encountered amelioration of the assayed hematological and biochemical parameters in animals treated with HgCl2 and given lactoferrin, it could be concluded that lactoferrin as a dietary supplement might function as an efficient antioxidant to alleviate the oxidative stress induced by mercury toxicity.

Transcranial ultrasound stimulation selectively affects cortical neurovascular coupling across neuronal types and LFP frequency bands.

Previous studies have affirmed that transcranial ultrasound stimulation (TUS) can influence cortical neurovascular coupling across low-frequency (0-2Hz)/high-frequency (160-200Hz) neural oscillations and hemodynamics. Nevertheless, the selectivity of this coupling triggered by transcranial ultrasound stimulation for spike activity (> 300Hz) and additional frequency bands (4-150Hz) remains elusive. We applied transcranial ultrasound stimulation to mice visual cortex while simultaneously recording total hemoglobin concentration, spike activity, and local field potentials. Our findings include (1) a significant increase in coupling strength between spike firing rates of putative inhibitory neurons/putative excitatory neurons and total hemoglobin concentration post-transcranial ultrasound stimulation; (2) an ~ 2.1-fold higher Pearson correlation coefficient between putative inhibitory neurons and total hemoglobin concentration compared with putative excitatory neurons and total hemoglobin concentration (*P< 0.05); (3) a notably greater cross-correlation between putative inhibitory neurons and total hemoglobin concentration than that between putative excitatory neurons and total hemoglobin concentration (*P< 0.05); (4) an enhancement of Pearson correlation coefficient between the relative power of γ frequency band (30-80Hz), hγ frequency band (80-150Hz) and total hemoglobin concentration following transcranial ultrasound stimulation (*P< 0.05); and (5) strongest cross-correlation observed at negative delay for θ frequency band, and positive delay for α, β, γ, hγ frequency bands. Collectively, these results demonstrate that cortical neurovascular coupling evoked by transcranial ultrasound stimulation exhibits selectivity concerning neuronal types and local field potential frequency bands.