Effects of Environmental Hypoxia on Serum Hematological and Biochemical Parameters, Hypoxia-Inducible Factor (hif) Gene Expression and HIF Pathway in Hybrid Sturgeon (Acipenser schrenckii ♂ × Acipenser baerii ♀).

Hypoxia is a globally pressing environmental problem in aquatic ecosystems. In the present study, a comprehensive analysis was performed to evaluate the effects of hypoxia on physiological responses (hematology, cortisol, biochemistry, hif gene expression and the HIF pathway) of hybrid sturgeons (Acipenser schrenckii ♂ × Acipenser baerii ♀). A total of 180 hybrid sturgeon adults were exposed to dissolved oxygen (DO) levels of 7.00 ± 0.2 mg/L (control, N), 3.5 ± 0.2 mg/L (moderate hypoxia, MH) or 1.00 ± 0.1 mg/L (severe hypoxia, SH) and were sampled at 1 h, 6 h and 24 h after hypoxia. The results showed that the red blood cell (RBC) counts and the hemoglobin (HGB) concentration were significantly increased 6 h and 24 h after hypoxia in the SH group. The serum cortisol concentrations gradually increased with the decrease in the DO levels. Moreover, several serum biochemical parameters (AST, AKP, HBDB, LDH, GLU, TP and T-Bil) were significantly altered at 24 h in the SH group. The HIFs are transcription activators that function as master regulators in hypoxia. In this study, a complete set of six hif genes were identified and characterized in hybrid sturgeon for the first time. After hypoxia, five out of six sturgeon hif genes were significantly differentially expressed in gills, especially hif-1α and hif-3α, with more than 20-fold changes, suggesting their important roles in adaptation to hypoxia in hybrid sturgeon. A meta-analysis indicated that the HIF pathway, a major pathway for adaptation to hypoxic environments, was activated in the liver of the hybrid sturgeon 24 h after the hypoxia challenge. Our study demonstrated that hypoxia, particularly severe hypoxia (1.00 ± 0.1 mg/L), could cause considerable stress for the hybrid sturgeon. These results shed light on their adaptive mechanisms and potential biomarkers for hypoxia tolerance, aiding in aquaculture and conservation efforts.

High-frequency photoacoustic and ultrasound imaging for skin evaluation: Pilot study for the assessment of a chemical burn.

Skin architecture and its underlying vascular structure could be used to assess the health status of skin. A non-invasive, high resolution and deep imaging modality able to visualize skin subcutaneous layers and vasculature structures could be useful for determining and characterizing skin disease and trauma. In this study, a multispectral high-frequency, linear array-based photoacoustic/ultrasound (PAUS) probe is developed and implemented for the imaging of rat skin in vivo. The study seeks to demonstrate the probe capabilities for visualizing the skin and its underlying structures, and for monitoring changes in skin structure and composition during a 5-day course of a chemical burn. We analayze composition of lipids, water, oxy-hemoglobin, and deoxy-hemoglobin (for determination of oxygen saturation) in the skin tissue. The study successfully demonstrated the high-frequency PAUS imaging probe was able to provide 3D images of the rat skin architecture, underlying vasculature structures, and oxygen saturation, water, lipids and total hemoglobin.

Association between maternal hemoglobin concentration and educational attainment in mid-childhood in a high-resource obstetric setting: a prospective cohort study.

BACKGROUND: Although maternal hemoglobin levels during pregnancy are commonly associated with perinatal outcomes, their link to childhood neurodevelopment remains uncertain. OBJECTIVE: This study aimed to examine the associations between maternal hemoglobin in early and late pregnancy and the educational attainment of offspring mid-childhood in a high-resource obstetric setting. STUDY DESIGN: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012, N=3285) were linked to mid-childhood educational outcomes (Department for Education, United Kingdom). Regression models adjusted for maternal, child, and socioeconomic factors were used to determine associations between maternal hemoglobin, pregnancy complications, and offspring educational outcomes (aged 5-7 years). RESULTS: No association was observed between maternal hemoglobin at 12 weeks and the likelihood of either adverse pregnancy outcomes or children meeting expected educational standards between ages 5-7 years. Higher maternal hemoglobin at 28 weeks was associated with an increased risk of small-for-gestational-age infants (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.59]; P=.002) and preterm birth (adjusted odds ratio, 1.38 [95% confidence interval, 1.11-1.81]; P=.005). There were no adverse birth outcomes associated with anemia. However, children of mothers who were anemic at 28 weeks had ∼40% increased risk of not attaining expected educational standards at age 5 (adjusted odds ratio, 1.42 [95% confidence interval, 1.03-1.95]; P=.03). There was no association between maternal anemia at 28 weeks and educational performance at ages 6-7. No associations were found between high maternal hemoglobin concentrations (top decile) or change in hemoglobin concentrations between 12 and 28 weeks and childhood educational attainment. CONCLUSION: Maternal anemia at 28 weeks of pregnancy is associated with reduced educational attainment at 5 years old but not at older ages (6-7 years old). A proactive approach to increasing maternal hemoglobin in high-resource settings is unlikely to impact long-term childhood educational attainment.

Extracorporeal membrane oxygenators with light-diffusing fibers for treatment of carbon monoxide poisoning: Experiments, mathematical modeling, and performance assessment with unit cells.

BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration. However, there are only a limited number of cases with ready accessibility to the specialized HBO chambers. In previous studies, we developed an extracorporeal veno-venous membrane oxygenator that facilitates exposure of blood to an external visible light source to photo-dissociate carboxyhemoglobin (COHb) and significantly increase CO removal from CO-poisoned blood (photo-extracorporeal veno-venous membrane oxygenator [p-ECMO]). One objective of this study was to describe in vitro experiments with different laser wavelength sources to compare CO elimination rates in a small unit-cell ECMO device integrated with a light-diffusing optical fiber. A second objective was to develop a mathematical model that predicts CO elimination rates in the unit-cell p-ECMO  device design upon which larger devices can be based. STUDY DESIGN/MATERIAL AND METHODS: Two small unit-cell p-ECMO devices consisted of a plastic capillary with a length and inside diameter of 10 cm and 1.15 mm, respectively. Either five (4-1 device) or seven (6-1 device) gas exchange tubes were placed in the plastic capillary and a light-diffusing fiber was inserted into one of the gas exchange tubes. Light from lasers emitting either 635 nm or 465 nm wavelengths was coupled into the light-diffusing fiber as oxygen flowed through the gas exchange membranes. To assess the ability of the device to remove CO from blood in vitro, the percent COHb reduction in a single pass through the device was assessed with and without light. The Navier Stokes equations, Carreau-Yesuda model, Boltzman equation for light distribution, and hemoglobin kinetic rate equations, including photo-dissociation, were combined in a mathematical model to predict COHb elimination in the experiments. RESULTS: For the unit-cell devices, the COHb removal rate increases with increased 635 nm laser power, increased blood time in the device, and greater gas exchange membrane surface-to-blood volume ratio. The 6-1 device COHb half-life versus that of the 4-1 device with 4 W at 635 nm light was 1.5 min versus 4.25 min, respectively. At 1 W laser power, 635 nm and 465 nm exhibited similar CO removal rates. The COHb half-life times of the 6-1 device were 1.25, 2.67, and 8.5 min at 635 nm (4 W), 465 nm (1 W), and 100% oxygen only, respectively. The mathematical model predicted the experimental results. An analysis of the in vivo COHb half-life of oxygen respiration therapy versus an adjunct therapy with a p-ECMO device and oxygen respiration shows a reduction from 90 min to as low as 10 min, depending on the device design. CONCLUSION: In this study, we experimentally studied and developed a mathematical model of a small unit-cell ECMO device integrated with a light-diffusing fiber illuminated with laser light. The unit-cell device forms the basis for a larger device and, in an adjunct therapy with oxygen respiration, has the potential to remove COHb at much higher rates than oxygen therapy alone. The mathematical model can be used to optimize the design in practical implementations to quickly and efficiently remove CO from CO-poisoned blood.

Biological Assessment of the NO-Dependent Endothelial Function.

Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.

Burden of Mild (<13 g/dl) Anemia in Patients With Atrial Fibrillation (A Report from a Multicenter Registry With Patient-Reported Outcomes).

The prognostic impact of anemia, especially mild anemia, in atrial fibrillation (AF) remains unclear. We examined clinical burdens of mild anemia on the quality of life (QoL) and clinical outcomes of 1,677 AF patients. Patients were divided into a non-anemia (hemoglobin [Hb] ≥13 g/dl for men and Hb ≥12 g/dl for women) and a mild anemia group (10≤ Hb <13 g/dl for men and 10≤ Hb <12 g/dl for women). At baseline, 22.5% of patients (n = 378) had anemia; patients in the mild anemia group had higher CHA2DS2-VASc scores (3.7 vs 2.7; p <0.01) and brain natriuretic peptide levels (253.5 vs 159.6 pg/ml; p <0.01) and were more likely to develop chronic kidney disease (64.2 vs 42.9%; p <0.01) than those in the non-anemia group. During follow-up (mean 1.7 ± 0.4 years), patients with mild anemia had a higher risk of heart failure hospitalization and major bleeding events than those without (12.2 vs 3.8%; p <0.01 and 5.6 vs 2.5%; p <0.01, respectively). Mild anemia was an independent risk factor for heart failure hospitalization (adjusted hazard ratio: 1.67, 95% confidence interval 1.06 to 2.62, p = 0.03) but not for major bleeding (adjusted hazard ratio: 1.44, 95% confidence interval 0.80 to 2.62, p = 0.23). QoL improvement was less likely in the mild anemia group during follow-up, despite the lack of significant differences at baseline. In conclusion, the presence of even mild anemia was associated with increased risks of heart failure hospitalization and poor QoL improvement.

Blood Lead Levels and Associated Sociodemographic Factors among Children Aged 3 to 14 Years Living near Zinc and Lead Mines in Two Provinces in Vietnam.

Lead poisoning in children is a major public health concern worldwide, especially in developing countries. We conducted a cross-sectional study on 403 children aged from 3 to 14 years living nearly zinc-lead mining areas in two provinces in Vietnam (Bac Kan and Thai Nguyen) from 06/2016 to 10/2016 to identify risk factors for lead contamination. Results. The proportion of children with blood lead levels (BLLs) ≥ 10 µg/dL was 80.51% in Bac Kan and 50% in Thai Nguyen; the mean blood lead level for children was 14.41 ± 9.42 µg/dL. In linear regression analyses, the body mass index was negatively associated with elevated BLLs with r = -0.404, p < 0.05 (95% CI: -0.801, -0.006). In multivariable regression analysis, several risk factors were associated with lead contamination including male sex (aOR = 2.44, 95% CI: 1.13-5.24, p = 0.02), play areas in Bac Kan (aOR = 2.3 (1.02-5.17), p = 0.04), proximity of children's home of less than 2 kilometers from the mine (aOR = 2.90 (1.54-5.44), p = 0.001), and inattentive symptoms in Thai Nguyen (aOR = 7.85, 95% CI 3.49-17.69, p = 0.001). Environmental factors, including lead concentrations in the soil and ambient air samples in both locations, are many times higher than Vietnamese standards.

Multidimentional Preoperative Frailty Assessment and Postoperative Complication Risk in Egyptian Geriatric Patients Undergoing Elective Cardiac Surgery.

BACKGROUND: Frailty affects up to 51%of the geriatric population in developing countries which leads to increased morbidity and mortality. OBJECTIVE: To determine the association between pre-operative frailty through multidimentional assessment score, and the incidence of post-operative complications and to validate Robinson score in geriatric Egyptian patients undergoing elective cardiac surgery. METHODS: We recruited 180 elderly participants aged 60 years old and above, who underwent elective cardiac surgery. They were divided into frail, pre-frail, and non-frail groups after application of Robinson score (which includes cognitive and functional and fall risk assessment, number of comorbidities, and different laboratory data). Type and duration of operations and the presence and severity of complications at days 3 and 7 post-surgery, and the 30-day readmission rate were assessed. RESULTS: Operation duration and the occurrence of postoperative complications at days 3 and 7 were lowest in non-frail and highest in the frail group (p < 0.001 for both). Length of hospital stay and 30-day readmission rate also increased in the frail group. A positive, moderate correlation between frailty and blood transfusion (r = 0.405) and functional dependence (r = 0.552) was found at day-3 post-surgery. Finally, logistic regression analysis identified a 6-fold increase in postoperative complications in the frail group (OR = 6). CONCLUSION: Preoperative frailty was associated with higher incidence of postoperative complications among geriatric patients undergoing elective cardiac surgery. Frailty assessment by Robinson score can be considered as an accurate tool to predict postoperative complications during preoperative assessment of elderly patients.

Online Noninvasive Assessment of Human Brain Death by Near-Infrared Spectroscopy with Protocol of O2 Inspiration.

Brain death is the irreversible loss of all the functions of the brain and brainstem. Compared to traditional diagnostic methods of brain death, near-infrared spectroscopy (NIRS) is a noninvasive, objective, cost-effective, and safe way of assessment of brain death. Eighteen brain dead patients and 20 healthy subjects were studied by NIRS, with a multiple-phase protocol at varied fractions of inspired O2 (FIO2). We found that the changes in the concentration ratios of oxyhemoglobin to deoxyhemoglobin (Δ[HbO2]/Δ[Hb]) in the cerebral cortex of brain dead patients were significantly higher than those of healthy subjects, and its low-to-high FIO2 phase was most sensitive, with a recommended threshold in the range 1.40-1.50. Our study indicated that NIRS is a promising technology for assessing brain death. The success of this application potentially offers a supplementary technique for the assessment of brain death in real time in order to be able to promptly offer quality-assured donor organs.

Conversion from Aranesp® to NESP® in dialysis patients-Exploration of dosing strategies and the feasibility of extending the dosing interval.

AIM: Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. METHODS: Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. RESULTS: Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. CONCLUSION: Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.

Characterizing Micronutrient Status and Risk Factors among Late Adolescent and Young Women in Rural Pakistan: A Cross-Sectional Assessment of the MaPPS Trial.

Nutritional deficiencies are a leading underlying risk factor contributing to the global burden of disease. In Pakistan, late adolescence is considered a nutritionally vulnerable period, as micronutrient requirements are increased to support maturation, and dietary staples are nutrient poor. However, there has been limited evaluation of micronutrient status beyond anemia and its determinants. Using cross-sectional data from late adolescent and young women (15-23 years) at enrolment in the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial, we aimed to describe the prevalence of key micronutrient deficiencies of public health concern, and generate hierarchical models to examine associations with proxies for social determinants of health (SDoH). The prevalence of micronutrient deficiencies was high: 53.6% (95% confidence interval (CI): 53.0-54.3%) had anemia; 38.0% (95% CI: 36.4-39.6%) iron deficiency anemia; 31.8% (95% CI: 30.2-33.3%) vitamin A deficiency; and 81.1% (95% CI: 79.8-82.4%) vitamin D deficiency. At least one deficiency was experienced by 91.0% (95% CI: 90.1-92.0%). Few SDoH were maintained in the final hierarchical models, although those maintained were often related to socioeconomic status (e.g., education, occupation). To improve the micronutrient status of late adolescent and young women in Pakistan, a direct micronutrient intervention is warranted, and should be paired with broader poverty alleviation methods.

Assessment of the analytical performance of point-of-care faecal immunochemical tests for haemoglobin.

BACKGROUND: The faecal immunochemical test (FIT) detects the presence of haemoglobin (Hb) in faeces. It is used as a screening tool for colorectal cancer (CRC) and increasingly to triage patients presenting with symptoms of CRC. A number of quantitative point-of-care (POC) FIT systems marketed for professional use and intended for use in a clinical setting are available. Here we reviewed the POC FIT systems available; three (Eurolyser Cube, OC-Sensor iO and QuikRead go) were evaluated to assess their performance against manufacturers' claims and suitability for use in a clinical setting. METHODS: The analytical evaluation of the POC FIT systems was undertaken using Hb lysates, patient samples and an external quality assessment sample. The evaluation focused on linearity, recovery, imprecision, prozone effect, Hb variant detection and suitability for use in a clinical setting. RESULTS: All three POC FIT systems performed to their manufacturer's claims and demonstrated good analytical performance with acceptable linearity, recovery, within- and between-run imprecision. The QuikRead go and OC-Sensor iO were able to accurately detect samples with results above their measuring range. However, because of a prozone effect the Eurolyser Cube gave falsely low results when using high concentrations of Hb. The QuikRead go performed best in the usability assessment due to portability and timeliness of result. CONCLUSION: Each system performed according to their manufacturers' claims. The QuikRead go and OC-Sensor iO are suitable for use. The Eurolyser Cube is not recommended because of the risk of falsely low results.

Identification of Allosteric Effects in Proteins by Elastic Network Models.

Allostery is a fundamental regulatory mechanism in the majority of biological processes of molecular machines. Allostery is well-known as a dynamic-driven process, and thus, the molecular mechanism of allosteric signal transmission needs to be established. Elastic network models (ENMs) provide efficient methods for investigating the intrinsic dynamics and allosteric communication pathways in proteins. In this chapter, two ENM methods including Gaussian network model (GNM) coupled with Markovian stochastic model, as well as the anisotropic network model (ANM), were introduced to identify allosteric effects in hemoglobins. Techniques on model parameters, scripting and calculation, analysis, and visualization are shown step by step.

Changes in hemoglobin levels with age and altitude in preschool-aged children in Peru: the assessment of two individual-based national databases.

According to the World Health Organization, the cutoff hemoglobin (Hb) value for defining anemia is 11 g/dL in preschool-aged children, and Hb measurements should be corrected above an altitude of 1000 meters. This study sought to determine the altitude at which the Hb value increases compared with that at sea level, Hb changes with age and region in Peru, the prevalence of anemia according to three different models used to correct Hb for altitude, and the association of the Hb value with stunting. Two individual-based Peruvian national databases were analyzed. Hb increased from an altitude of 375 meters. Hb concentration was lower at younger ages and higher at older ages. The increase in Hb with increasing altitude was lower in southern Peru. Implementing the different models for Hb measurement correction resulted in a higher and lower prevalence of anemia at altitudes >2500 and <2500 m, respectively, using the CDC adjustment. In children aged 6-23 months, the rate of stunting was lower in those with an Hb level of 10-12 g/dL (including mild anemia). In conclusion, the adjustment of Hb values for altitude should be considered before 1000 m and reference ranges should be adjusted to smaller groups of children instead of the same reference range for children aged 6-59 months.

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer.

Blood transport proteins are biogenic molecules with unique and interesting inherent characteristics that make up living organisms. As the utilization of their inherent characteristics can be a groundbreaking strategy to resolve and improve several clinical problems, attempts have been made to develop pharmaceutical and biomedical preparations based on blood transport proteins for the treatment and diagnosis of disorders. Among various blood transport proteins, we focus on the immense potential of hemoglobin and albumin to serve as carriers of biomedical gases (oxygen and carbon monoxide) and anticancer agents (low-molecular compounds and antisense oligodeoxynucleotides), respectively, for the development of innovative drug delivery systems (DDS) to treat intractable disorders and solid cancers. In this review, I introduce the pharmaceutical technology, strategies, and application of DDS carriers that have been designed on the basis of the structure and function of hemoglobin and albumin. In addition, the prospect of using hemoglobin and albumin as materials for DDS carriers is discussed.

Differential effects of socio-demographic factors on maternal haemoglobin concentration in three sub-Saharan African Countries.

Low Haemoglobin concentration (Hb) among women of reproductive age is a severe public health problem in sub-Saharan Africa. This study investigated the effects of putative socio-demographic factors on maternal Hb at different points of the conditional distribution of Hb concentration. We utilised quantile regression to analyse the Demographic and Health Surveys data from Ghana, Democratic Republic of the Congo (DRC) and Mozambique. In Ghana, maternal schooling had a positive effect on Hb of mothers in the 5th and 10th quantiles. A one-year increase in education was associated with an increase in Hb across all quantiles in Mozambique. Conversely, a year increase in schooling was associated with a decrease in Hb of mothers in the three upper quantiles in DRC. A unit change in body mass index had a positive effect on Hb of mothers in the 5th, 10th, 50th and 90th, and 5th to 50th quantiles in Ghana and Mozambique, respectively. We observed differential effects of breastfeeding on maternal Hb across all quantiles in the three countries. The effects of socio-demographic factors on maternal Hb vary at the various points of its distribution. Interventions to address maternal anaemia should take these variations into account to identify the most vulnerable groups.

The Critical Choice of Animal Models in Nanomedicine Safety Assessment: A Lesson Learned From Hemoglobin-Based Oxygen Carriers.

Intravenous injection of nanopharmaceuticals can induce severe hypersensitivity reactions (HSRs) resulting in anaphylactoid shock in a small percentage of patients, a phenomenon explicitly reproducible in pigs. However, there is a debate in the literature on whether the pig model of HSRs can be used as a safety test for the prediction of severe adverse reactions in humans. Given the importance of using appropriate animal models for toxicity/safety testing, the choice of the right species and model is a critical decision. In order to facilitate the decision process and to expand the relevant information regarding the pig or no pig dilemma, this review examines an ill-fated clinical development program conducted by Baxter Corporation in the United States 24 years ago, when HemeAssist, an αα (diaspirin) crosslinked hemoglobin-based O2 carrier (HBOC) was tested in trauma patients. The study showed increased mortality in the treatment group relative to controls and had to be stopped. This disappointing result had far-reaching consequences and contributed to the setback in blood substitute research ever since. Importantly, the increased mortality of trauma patients was predicted in pig experiments conducted by US Army scientists, yet they were considered irrelevant to humans. Here we draw attention to that the underlying cause of hemoglobin-induced aggravation of hemorrhagic shock and severe HSRs have a common pathomechanism: cardiovascular distress due to vasoconstrictive effects of hemoglobin (Hb) and reactogenic nanomedicines, manifested, among others, in pulmonary hypertension. The main difference is that in the case of Hb this effect is due to NO-binding, while nanomedicines can trigger the release of proinflammatory mediators. Because of the higher sensitivity of cloven-hoof animals to this kind of cardiopulmonary distress compared to rodents, these reactions can be better reproduced in pigs than in murine or rat models. When deciding on the battery of tests and the appropriate models to identify the potential hazard for nanomedicine-induced severe HSR, the pros and cons of the various species must be considered carefully.

Preliminary assessment of the new Sysmex XN parameter Iron-Def for identifying iron deficiency.

BACKGROUND: Although the clinical assessment of iron status is usually based on iron stores, a rapid and accurate diagnosis of iron deficiency is challenging since ferritin is often unavailable as an urgent test and its value is frequently increased in acute phase conditions. This study was therefore aimed at evaluating the diagnostic performance of the new Sysmex XN "Iron Deficiency?" (Iron-Def) parameter for identifying patients with iron deficiency. MATERIALS AND METHODS: The study population consisted of 688 consecutive patients (median age: 71 years; 341 women and 347 men), referred for routine diagnostics to the Laboratory of Clinical Pathology of Lecco Hospital, Italy. A complete clinical chemistry profile and haematological testing were performed for identifying iron deficiency anaemia. RESULTS: A significant negative correlation was found between Sysmex XN Iron-Def and ferritin, serum iron, mean cell haemoglobin concentration, mean cell haemoglobin, mean corpuscular volume and age, while a positive correlation was noted with transferrin, percentage of microcytic red cell, red blood cell count and red blood cell distribution width. The diagnostic accuracy of Iron-Def for identifying patients with a percentage of saturation of transferrin <15% (n=104) was 84%, with a sensitivity of 0.952 and specificity of 0.538. A sub-analysis of 71 patients with ferritin <20 ng/dL yielded an even better diagnostic performance (86%, with a sensitivity of 0.935 and specificity of 0.620). DISCUSSION: Although additional confirmatory investigations would be needed, the preliminary findings of our study attest that Iron-Def may be an easy, inexpensive, rapid and reliable parameter for screening iron deficiency anaemia.

Physiological wound assessment from coregistered and segmented tissue hemoglobin maps.

A handheld near-infrared optical scanner (NIROS) was recently developed to map for effective changes in oxy- and deoxyhemoglobin concentration in diabetic foot ulcers (DFUs) across weeks of treatment. Herein, a coregistration and image segmentation approach was implemented to overlay hemoglobin maps onto the white light images of ulcers. Validation studies demonstrated over 97% accuracy in coregistration. Coregistration was further applied to a healing DFU across weeks of healing. The potential to predict changes in wound healing was observed when comparing the coregistered and segmented hemoglobin concentration area maps to the visual area of the wound.