Total Hemoglobin Concentration Research Articles

Caloric Vestibular Stimulation Alleviates Cold Water Swimming Stress Induced Changes in BDNF and Haematological Parameters

Introduction: Stress is inevitable in daily life. Stress in long term has been implicated in the development of physical and neuronal disorders. Various studies have described the levels and role of BDNF in the brain following stress. Studies representing the changes in serum BDNF and wet weight of organs in stress are limited and controversial. Aim: The aim of the present study is to find the effect of stress on serum BDNF concentration, wet weight of selected organs, haematological parameters and to evaluate the effectiveness of caloric vestibular stimulation on stress-induced changes in these parameters. Methods and material: Male Wistar rats were exposed to cold water swimming stress for 14 days for a duration of 30 minutes per day. Serum corticosterone and serum BDNF were measured using the ELISA method. Weight of liver, spleen, thymus and lymph nodes were measured and their relation to body weight was calculated. Total RBC count, total WBC count, platelet count and haemoglobin concentration were analysed. Results: A statistically significant increase in serum corticosterone and BDNF was observed following stress. Liver weight, thymus weight and lymph nodes weight did not show any significant changes but spleen weight has reduced in the normal recovery group following stress. Total RBC count, total WBC count, platelet count and haemoglobin levels were significantly higher in the stress group. Caloric vestibular stimulation was effective in managing stress-induced changes in serum corticosterone, BDNF and spleen weight. Conclusion: Caloric vestibular stimulation is effective in restoring the stress-induced changes.

Dataset of human skin and fingernails images for non-invasive haemoglobin level assessment

Anaemia, a decrease in total concentration of haemoglobin (Hb) in blood, affects substantial percentage of the population worldwide. Currently, the gold standard for determining the Hb level is the invasive analysis of venous blood. Yet, more and more research groups demonstrate the possibility of non-invasive Hb assessment using white light imaging of tissue sites where Hb is the main chromophore, in particular, fingernails. Despite the promising declarations, non-invasive Hb assessment via RGB-imaging is still poorly used in practice. The main reason is the difficulty in establishing the true accuracy of the methods presented in different works since they are tested on private datasets collected under different experimental conditions. Here we present an open dataset containing RGB images of skin and fingernails for patients with a known level of Hb, thus providing a single benchmark for researchers and engineers in the field, aimed at fostering translation of non-invasive imaging methods to the bedside.

Investigating Skeletal Muscle Pump Function Using Thigh EMG, Thigh NIRS, And Stroke Volume Data In The FRAILMatics Physiological Cohort

Abstract Background The pioneering female physiologist Frances Hellebrandt first highlighted the significance of the skeletal muscle pump in circulation in the 1930s. However, the mechanisms underlying the muscle pump's function remain elusive, particularly in older individuals. It is thought that during muscle contraction, increased intramuscular pressure facilitates the expulsion of blood from the muscle's veins, aiding venous return. This contraction-induced pressure gradient assists in pushing blood towards the heart, increasing preload, and subsequently stroke volume (SV). In this study we investigated muscle pump activity using continuous measurements of thigh muscle activity, thigh total haemoglobin concentration (Hb), and cardiac SV. Methods 22 individuals (aged 70.8±5.3 years, 77.3% female) recruited from a Falls and Syncope Unit (St James’s Hospital, Dublin) underwent non-invasive measurements of Hb (NIRS PortaLite, Artinis Medical Systems, The Netherlands), electromyography (EMG) (Shimmer3, Research Ltd, Ireland), and SV (Finapres Nova, Finapres Medical Systems, The Netherlands) during a 10-second thigh squeeze test. Pre-processing involved data quality checks, alignment, and resampling. 60-second regions of interest were extracted, normalised, and processed using MATLAB (R2023a, TheMathWorks, Inc., Natick, MA, USA). Cross-correlation and Granger causality analyses were conducted to explore relationships between signals. Results Thigh Hb and EMG signals lagged 8.4 and 8.5 seconds behind SV, respectively. Granger Causality analysis revealed a significant causal relationship from both Hb and EMG to SV in 68% of participants at measured lags. Conclusion The observed ~8.5-second lag between thigh measurements and SV implies a plausible temporal relationship between muscle activation and venous return, further supported by significant causal relationships found in a substantial portion of participants using Granger causality analysis. These findings underscore the importance of continued research in this area, not only for advancing our understanding of physiological mechanisms but also for informing potential clinical applications aimed at optimising cardiovascular health and function.

Diffuse optical spectroscopy of lactating and non-lactating human mammary physiology.

Breastfeeding provides widely recognized advantages for infant and maternal health. Unfortunately, many women experience trouble with breastfeeding. Nevertheless, few suitable imaging modalities are available to study human lactation and determine the possible causes of breastfeeding problems. In this study, we apply broadband, quantitative diffuse optical spectroscopy (DOS) for this purpose. We present a study of fourteen lactating and eight similarly aged, premenopausal, non-lactating women to investigate the feasibility of DOS to study the optical and physiological differences between 1) lactating and non-lactating breasts, 2) the areolar and non-areolar region within the breast, and 3) lactating breasts before and after milk extraction. Our study shows that i) the median total hemoglobin concentration [tHb] of the lactating breast is 51% higher than for the non-lactating breast. ii) the median [tHb] of the lactating breast is 37% higher in the areolar region compared to the non-areolar region. iii) lactating breasts exhibit a positive median difference of 8% in [tHb] after milk extraction. Our findings are consistent with the expected physiological changes that occur during the lactation period. Importantly, we show that DOS provides unique insight into breast tissue composition and physiology, serving as a foundation for future application of the technique in lactation research.

Prediction of disease-free survival using strain elastography and diffuse optical tomography in patients with T1 breast cancer: a 10-year follow-up study

BackgroundEarly-stage breast cancer (BC) presents a certain risk of recurrence, leading to variable prognoses and complicating individualized management. Yet, preoperative noninvasive tools for accurate prediction of disease-free survival (DFS) are lacking. This study assessed the potential of strain elastography (SE) and diffuse optical tomography (DOT) for non-invasive preoperative prediction of recurrence in T1 BC and developed a prediction model for estimating the probability of DFS.MethodsA total of 565 eligible patients with T1 invasive BC were enrolled prospectively and followed to investigate the recurrence. The associations between imaging features and DFS were evaluated and a best-prediction model for DFS was developed and validated.ResultsDuring the median follow-up period of 10.8 years, 77 patients (13.6%) developed recurrences. The fully adjusted Cox proportional hazards model showed a significant trend between an increasing strain ratio (SR) (P < 0.001 for trend) and the total hemoglobin concentration (TTHC) (P = 0.001 for trend) and DFS. In the subgroup analysis, an intensified association between SR and DFS was observed among women who were progesterone receptor (PR)-positive, lower Ki-67 expression, HER2 negative, and without adjuvant chemotherapy and without Herceptin treatment (all P < 0.05 for interaction). Significant interactions between TTHC status and the lymphovascular invasion, estrogen receptor (ER) status, PR status, HER2 status, and Herceptin treatment were found for DFS(P < 0.05).The imaging–clinical combined model (TTHC + SR + clinicopathological variables) proved to be the best prediction model (AUC = 0.829, 95% CI = 0.786–0.872) and was identified as a potential risk stratification tool to discriminate the risk probability of recurrence.ConclusionThe combined imaging-clinical model we developed outperformed traditional clinical prognostic indicators, providing a non-invasive, reliable tool for preoperative DFS risk stratification and personalized therapeutic strategies in T1 BC. These findings underscore the importance of integrating advanced imaging techniques into clinical practice and offer support for future research to validate and expand on these predictive methodologies.

Prediction of the response to antiangiogenic sunitinib therapy by non-invasive hybrid diffuse optics in renal cell carcinoma.

In this work, broadband diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) were used to quantify deep tissue hemodynamics in a patient-derived orthotopic xenograft mouse model of clear cell renal cancer undergoing antiangiogenic treatment. A cohort of twenty-two mice were treated with sunitinib and compared to thirteen control untreated mice, and monitored by DRS/DCS. A reduction in total hemoglobin concentration (THC, p = 0.03), oxygen saturation (SO2, p = 0.03) and blood flow index (BFI, p = 0.02) was observed over the treatment course. Early changes in tumor microvascular blood flow and total hemoglobin concentration were correlated with the final microvessel density (p = 0.014) and tumor weight (p = 0.024), respectively. Higher pre-treatment tumor microvascular blood flow was observed in non-responder mice with respect to responder mice, which was statistically predictive of the tumor intrinsic resistance (p = 0.01). This hybrid diffuse optical technique provides a method for predicting tumor intrinsic resistance to antiangiogenic therapy and could be used as predictive biomarker of response to antiangiogenic therapies in pre-clinical models.

Hyperspectral imaging of 4T1 mammary carcinomas grown in dorsal skinfold window chambers: spectral renormalization and fluorescence modeling.

Hyperspectral imaging (HSI) of murine tumor models grown in dorsal skinfold window chambers (DSWCs) offers invaluable insight into the tumor microenvironment. However, light loss in a glass coverslip is often overlooked, and particular tissue characteristics are improperly modeled, leading to errors in tissue properties extracted from hyperspectral images. We highlight the significance of spectral renormalization in HSI of DSWC models and demonstrate the benefit of incorporating enhanced green fluorescent protein (EGFP) excitation and emission in the skin tissue model for tumors expressing genes to produce EGFP. We employed an HSI system for intravital imaging of mice with 4T1 mammary carcinoma in a DSWC over 14 days. We performed spectral renormalization of hyperspectral images based on the measured reflectance spectra of glass coverslips and utilized an inverse adding-doubling (IAD) algorithm with a two-layer murine skin model, to extract tissue parameters, such as total hemoglobin concentration and tissue oxygenation ( ). The model was upgraded to consider EGFP fluorescence excitation and emission. Moreover, we conducted additional experiments involving tissue phantoms, human forearm skin imaging, and numerical simulations. Hyperspectral image renormalization and the addition of EGFP fluorescence in the murine skin model reduced the mean absolute percentage errors (MAPEs) of fitted and measured spectra by up to 10% in tissue phantoms, 0.55% to 1.5% in the human forearm experiment and numerical simulations, and up to 0.7% in 4T1 tumors. Similarly, the MAPEs for tissue parameters extracted by IAD were reduced by up to 3% in human forearms and numerical simulations. For some parameters, statistically significant differences ( ) were observed in 4T1 tumors. Ultimately, we have shown that fluorescence emission could be helpful for 4T1 tumor segmentation. The results contribute to improving intravital monitoring of DWSC models using HSI and pave the way for more accurate and precise quantitative imaging.

A study on the effects of transcranial direct current stimulation combined with motor imagery on brain function based on electroencephalogram and near infrared spectrum

Motor imagery is often used in the fields of sports training and neurorehabilitation for its advantages of being highly targeted, easy to learn, and requiring no special equipment, and has become a major research paradigm in cognitive neuroscience. Transcranial direct current stimulation (tDCS), an emerging neuromodulation technique, modulates cortical excitability, which in turn affects functions such as locomotion. However, it is unclear whether tDCS has a positive effect on motor imagery task states. In this paper, 16 young healthy subjects were included, and the electroencephalogram (EEG) signals and near-infrared spectrum (NIRS) signals of the subjects were collected when they were performing motor imagery tasks before and after receiving tDCS, and the changes in multiscale sample entropy (MSE) and haemoglobin concentration were calculated and analyzed during the different tasks. The results found that MSE of task-related brain regions increased, oxygenated haemoglobin concentration increased, and total haemoglobin concentration rose after tDCS stimulation, indicating that tDCS increased the activation of task-related brain regions and had a positive effect on motor imagery. This study may provide some reference value for the clinical study of tDCS combined with motor imagery.

Diffuse reflectance spectroscopy for optical characterizations of orthotopic head and neck cancer models in vivo.

We demonstrated an easy-to-build, portable diffuse reflectance spectroscopy device along with a Monte Carlo inverse model to quantify tissue absorption and scattering-based parameters of orthotopic head and neck cancer models in vivo. Both tissue-mimicking phantom studies and animal studies were conducted to verify the optical spectroscopy system and Monte Carlo inverse model for the accurate extraction of tissue optical properties. For the first time, we reported the tissue absorption and scattering coefficients of mouse normal tongue tissues and tongue tumor tissues. Our in vivo animal studies showed reduced total hemoglobin concentration, lower tissue vascular oxygen saturation, and increased tissue scattering in the orthotopic tongue tumors compared to the normal tongue tissues. Our data also showed that mice tongue tumors with different sizes may have significantly different tissue absorption and scattering-based parameters. Small tongue tumors (volume was ∼60 mm3) had increased absorption coefficients, decreased reduced-scattering coefficients, and increased total hemoglobin concentrations compared to tiny tongue tumors (volume was ∼18 mm3). These results demonstrated the potential of diffuse reflectance spectroscopy to noninvasively evaluate tumor biology using orthotopic tongue cancer models for future head and neck cancer research.

Effects of dietary fermented Saccharomyces cerevisiae extract (Hilyses) supplementation on growth, hematology, immunity, antioxidants, and intestinal health in Nile tilapia

This study investigated the effects of dietary supplementation with the product Hilyses on growth performance, feed utilization, nutrient composition, hematological parameters, serum biochemistry, immune function, antioxidant status, and digestive enzyme activity in juvenile Nile tilapia (Oreochromis niloticus, initial body weight 4.24 ± 0.01 g). The fish were fed diets supplemented with Hilyses at concentrations of 0, 1, 2, or 3 g/kg for a period of 8 weeks. The results showed that supplementation with Hilyses at levels up to 2 g/kg diet significantly improved final body weight, weight gain, specific growth rate, feed efficiency ratio, protein efficiency ratio, apparent protein utilization, and energy utilization compared to the control diet without Hilyses. Carcass crude protein content and moisture were significantly higher in Hilyses-fed groups, while crude lipid content decreased at the 3 g/kg supplementation level. Hilyses supplementation enhanced various hematological parameters, including increased red blood cell count, total leukocyte count, hemoglobin concentration, hematocrit, and mean corpuscular volume. Serum biochemistry and immune function markers like total protein, albumin, complement component C3, IgM, and IgG were significantly elevated in the 2 and 3 g/kg Hilyses groups. Antioxidant enzyme activities (catalase, glutathione peroxidase, total superoxide dismutase) were enhanced, and lipid peroxidation was reduced, in the 2 g/kg Hilyses group. Digestive enzyme activities, particularly protease and lipase, were also improved with Hilyses supplementation. Histological examination showed reduced lipid deposition in the liver and increased branching of intestinal villi at the 2 g/kg Hilyses level. Overall, these results indicated that dietary Hilyses supplementation at 2 g/kg diet optimizes growth, feed utilization, nutrient composition, hematology, immunity, antioxidant status, and digestive function in juvenile Nile tilapia.

#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 &amp;gt; 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.