Evaluation of inflammatory biomarkers and the ratio of hemoglobin-red cell distribution width in patients with rheumatoid arthritis treated with tumor necrosis factor-alpha inhibitors.

BACKGROUND: The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. MATERIAL AND METHODS: The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. RESULTS: According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. CONCLUSION: Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors.

Newborn screening in Colombia: The experience of a private program in Bogotá / Tamizaje neonatal en Colombia: la experiencia de un programa privado en Bogotá.

Introduction. The first neonatal screening program in Colombia ­ PREGEN ­ was set up in the medical private sector of Bogotá in 1988. We report the results from recent years that, given the scarcity of similar information in our country, may help estimate the frequency of the evaluated neonatal disorders and which ones should be included in the neonatal screening programs in our country. Objective. To describe the results of PREGEN´s newborn screening program between 2006 and 2019. Materials and methods. We analyzed databases and other informative documents preserved in PREGEN from the 2006-2019 period. Results. One in every 164 newborns screened in our program had an abnormal hemoglobin variant, and one in every 194 carried some hemoglobin S variant. Glucose-6- phosphate dehydrogenase deficiency and congenital hypothyroidism are next as the more common disorders. Conclusions. Abnormal hemoglobin causes the most frequent monogenic disorder in the world. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymopathy affecting nearly 400 million individuals worldwide. Since both disorders are more common in people of African descent and confer some resistance to malaria, we believe that screening for both disorders may be more relevant in the areas with African ancestry in our country.

Introducción. En Colombia, el primer programa de tamizaje neonatal, PREGEN, inició labores en el sector privado de Bogotá en 1988. En este artículo se presentan los resultados obtenidos en los últimos años, que, dada la carencia de estos estudios en el país, pueden servir para evaluar la frecuencia de aparición de los trastornos congénitos evaluados y estimar cuáles de ellos deben ser objeto de tamizaje neonatal a nivel nacional. Objetivos. Reportar los resultados del programa de tamizaje PREGEN entre el 2006 y el 2019. Materiales y métodos. Para este análisis se examinaron las bases de datos y otros documentos informativos de PREGEN para el periodo 2006-2019. Resultados. Uno de cada 164 recién nacidos tamizados en el programa PREGEN en Bogotá presentó una variante anormal de la hemoglobina y uno de cada 194 es portador de hemoglobina S. Los siguientes dos trastornos más frecuentes encontrados fueron la deficiencia de la enzima glucosa-6-fosfato deshidrogenasa (frecuencia 1:2.231) y el hipotiroidismo congénito (frecuencia 1:3.915). Conclusiones. Las hemoglobinopatías mostraron ser uno de los desórdenes monogénicos más comunes, seguidos por la deficiencia de glucosa-6-fosfato deshidrogenasa y el hipotiroidismo congénito. Se calcula que cerca de 400 millones de personas en el mundo están afectadas por la deficiencia de glucosa-6-fosfato deshidrogenasa, por lo cual es la enzimopatía más común en el mundo. Como ambos desórdenes son más frecuentes en poblaciones de origen africano y confieren algún grado de resistencia a la malaria, es de prever que su tamizaje debe ser de mayor importancia en las zonas con ancestros africanos en Colombia.

High-Oxygen-Affinity Hemoglobins-Case Series and Review of the Literature.

Modifications of the hemoglobin (Hb) structure in regions involving the regulation of oxygen transport may lead to an increased oxygen affinity for the hemoglobin molecule and impaired oxygen delivery to the tissues. Herein, we present six patients with high-oxygen-affinity Hb variants, either in heterozygous form or in compound heterozygosity (such as heterozygosity for Hb Hiroshima, Köln, Crete, and compound heterozygosity Hb Crete with ß or 뫧 thalassemia), in order to demonstrate the need for prompt and accurate diagnosis and enrich the limited literature due to the rarity of such cases. Hb Crete, Hb Hiroshima, and Hb Köln have distinct pathophysiologies and may result in different clinical phenotypes. In conclusion, high-oxygen-affinity hemoglobins are rare and inherited within a dominant autosomal manner, have various clinical presentations, and should always be suspected in patients with erythrocytosis. Their management (as phlebotomy or low-dose aspirin) should be based on an individualized assessment of the risk of complications, the medical history, concomitant symptoms, and quality of life.

Dynamics of hemoglobins during nodule development, nitrate response, and dark stress in Lotus japonicus.

Legume nodules express multiple leghemoglobins (Lbs) and non-symbiotic hemoglobins (Glbs), but how they are regulated is unclear. Here, we study the regulation of all Lbs and Glbs of Lotus japonicus in different physiologically relevant conditions and mutant backgrounds. We quantified hemoglobin expression, localized reactive oxygen species (ROS) and nitric oxide (NO) in nodules, and deployed mutants deficient in Lbs and in the transcription factors NLP4 (associated with nitrate sensitivity) and NAC094 (associated with senescence). Expression of Lbs and class 2 Glbs was suppressed by nitrate, whereas expression of class 1 and 3 Glbs was positively correlated with external nitrate concentrations. Nitrate-responsive elements were found in the promoters of several hemoglobin genes. Mutant nodules without Lbs showed accumulation of ROS and NO and alterations of antioxidants and senescence markers. NO accumulation occurred by a nitrate-independent pathway, probably due to the virtual disappearance of Glb1-1 and the deficiency of Lbs. We conclude that hemoglobins are regulated in a gene-specific manner during nodule development and in response to nitrate and dark stress. Mutant analyses reveal that nodules lacking Lbs experience nitro-oxidative stress and that there is compensation of expression between Lb1 and Lb2. They also show modulation of hemoglobin expression by NLP4 and NAC094.

Noninvasive hemoglobin monitoring for maintaining hemoglobin concentration within the target range during major noncardiac surgery: A randomized controlled trial.

STUDY OBJECTIVE: The effect of noninvasive CO-oximetry hemoglobin (SpHb) monitoring on the clinical outcomes of patients undergoing surgery remains unclear. This trial aimed to evaluate whether SpHb monitoring helps maintain hemoglobin levels within a predefined target range during major noncardiac surgeries with a potential risk of intraoperative hemorrhage. DESIGN: A single-center, prospective, randomized controlled trial. SETTING: University hospital. PATIENTS: One hundred and thirty patients undergoing elective noncardiac surgery with a potential risk of hemorrhage. INTERVENTIONS: Patients were randomly allocated to undergo either SpHb-guided management (SpHb group) or usual care (control group). MEASUREMENTS: The primary outcome was the rate of deviation of the total hemoglobin concentration (determined from laboratory testing) from a pre-specified target range (8-14 g/dL). This was defined as the number of laboratory tests revealing such deviations divided by the total number of laboratory tests performed during the surgery. MAIN RESULTS: The primary outcome occurred significantly less frequently in the SpHb group as compared to that in the control group (15/555 [2.7%]) vs. 68/598 [11.4%]; relative risk, 0.24; 95% confidence interval, 0.13-0.41; P < 0.001). Fewer point-of-care blood tests were performed in the SpHb group than in the control group (median [interquartile range], 2 [1-4] vs. 4 [2-5]; P < 0.001). There were no significant intergroup differences in the number of patients who received red blood cell transfusions during surgery (SpHb vs. control, 33.8% vs. 46.2%; P = 0.201). The incidence of unnecessary red blood cell preparation (>2 units) was lower in the SpHb group than in the control group (3.1% vs. 16.9%; P = 0.024). CONCLUSIONS: Compared with routine care, SpHb-guided management resulted in significantly lower rates of hemoglobin deviation outside the target range intraoperatively in patients undergoing major noncardiac surgeries with a potential risk of hemorrhage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03816514).

Utilization of dapsone and hemoglobin in the epithelial skin regeneration therapy of cutaneous loxoscelism: A case report and integrative literature review

ABSTRACT BACKGROUND: Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their severity and location, cutaneous forms are managed with local cold application and systemic administration of antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics. OBJECTIVE: This study aimed to report a case of cutaneous loxoscelism and to identify the main dermatological manifestations associated with the Loxosceles spp bite. DESIGN AND SETTING: This case report and literature review was conducted in a Mexican university. METHODS: A detailed report on the medical management of a patient with cutaneous loxoscelism treated at the emergency department of a public hospital was published. Scopus, PubMed, Web of Science, and Google Scholar databases were searched to identify articles reporting cutaneous loxoscelism. The following keywords were used during the database search: "loxoscelism" OR "spider bite," OR "loxosceles" OR "loxosceles species" OR "loxosceles venom" OR "loxoscelism case report" AND "cutaneous" OR "dermonecrotic arachnidism." RESULTS: A 62-year-old female patient with cutaneous loxoscelism was treated with systemic dapsone and local heparin spray. Eighteen studies with 22 clinical cases were included in this systematic review. Of the 22 patients, 12 (54.5%) were men. L. rufescens was the predominant spider species. CONCLUSIONS: The administration of dapsone and heparin for the management of cutaneous loxoscelism demonstrated success in this case, with no sequelae observed. In general, the literature review indicated favorable outcomes in patients treated with antimicrobials and corticosteroids, with continuous healing of skin lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42023422424 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023422424).

Hemoglobin/Red Cell Distribution Width Ratio is Associated With Poor Prognosis in Patients With Acute Coronary Syndrome in Long-Term Follow-Up

Abstract Background Acute coronary syndrome (ACS) is the most common subtype of coronary artery disease (CAD). It is one of the main reasons affecting the expected life expectancy and quality of life. Objetives In this study, we aimed to investigate the relationship between major adverse cardiac events (MACE) and Hemoglobin (Hb)/Red cell distribution width (RDW) in long-term follow-up after ACS. Methods A total of 1,146 ACS patients were included in the study, being classified according to the type of myocordial infarction (MI). MACE were recorded in long-term follow-up. The relationship between Hb/RDW and MACE was investigated. The statistical analyses of Mann-Whitney U test for comparison of two independent groups and chi-square test for categorical variables were used. In order to determine the diagnostic feature of the HB/RDW ratio, the diagnostic ratios were calculated by applying Receiver Operating Characteristic Curve (ROC) analysis. A p < 0.05 value was considered statistically significant in all analyses. Results: When the patients were analyzed according to MI types — ST segment elevation myocardial infarction (STEMI)/Non-ST segment elevation myocardial infarction (NSTEMI) —, it was observed that Hb/RDW (p = 0.038) was significantly higher in the STEMI group. The Hb/RDW ratio was statistically significant in predicting mortality. As a result of ROC analysis, Area Under the Curve (AUC) = 0.654 (p < 0.001) was found. The cut-off value for the Hb/RDW ratio was calculated as 0.947. The sensitivity and specificity of 76.9% and 48.4% for the diagnostic rates obtained were moderately acceptable. Conclusion The Hb/RDW-long-term mortality relationship was found to be significant in ROC analysis. It can be used in clinical practice as it is cheap, easy to apply, and reduces possible bias in post-ACS follow-up.

Effect of enhanced recovery after surgery with multidisciplinary collaboration on nursing outcomes after total knee arthroplasty.

BACKGROUND: There is a lack of studies on the effects of enhanced recovery after surgery (ERAS) with multidisciplinary collaboration on the nursing outcomes of total knee arthroplasty (TKA). AIM: To explore the effect of ERAS with multidisciplinary collaboration on nursing outcomes after TKA. METHODS: We retrospectively analyzed the clinical data of 80 patients who underwent TKA at a tertiary hospital between January 2021 and December 2022. The patients were divided into two groups according to the nursing mode: the ERAS group (n = 40) received ERAS with multidisciplinary collaboration, and the conventional group (n = 40) received routine nursing. The following indicators were compared between the two groups: length of hospital stay, hospitalization cost, intraoperative blood loss, hemoglobin level 24 h after surgery, visual analog scale (VAS) score for pain, range of motion (ROM) of the knee joint, Hospital for Special Surgery (HSS) knee score, and postoperative complications. RESULTS: The ERAS group had a significantly shorter length of hospital stay, lower hospitalization cost, less intraoperative blood loss, higher hemoglobin level 24 h after surgery, lower VAS score for pain, higher knee joint ROM, and higher HSS knee score than the conventional group (all P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P > 0.05). CONCLUSION: Multidisciplinary collaboration with ERAS can reduce blood loss, shorten hospital stay, and improve knee function in patients undergoing TKA.

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causative of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV-2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, that were fundamental for the reduction of the viral spread within the population and the clinical severity of COVID-19. However, the S-protein has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. Considering the impact of COVID-19 and SARS-CoV-2 infection on the hematopoietic system, the aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. In this context, we focused on hemoglobin production and induced expression of embryo-fetal globin genes, that are among the most important features of K562 erythroid differentiation. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-qPCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination.

Using multi-channel near-infrared spectroscopy to assess the effect of cupping therapy on the spatial hemodynamic response of the biceps muscle: A preliminary study.

BACKGROUND: The local hemodynamic response after cupping therapy has been considered as a contributing factor for improving muscle tissue health; however, the effects of cupping pressure and duration on the spatial hemodynamic response have not been investigated. OBJECTIVE: The objective of this study was to investigate the hemodynamic response inside and outside the cupping cup under various pressures and durations of cupping therapy. METHODS: A 3-way factorial design with repeated measures was used to investigate the main and interaction effects of the location (areas inside and outside the cup), pressure (-225 and -300 mmHg) and duration (5 and 10 min) on the hemodynamic response of the biceps muscle. A functional near-infrared spectroscopy was used to assess hemodynamic changes in 18 participants. RESULTS: A significant three-way interaction of the location, pressure, and duration factors was observed in oxyhemoglobin (p= 0.023), deoxy-hemoglobin (p= 0.013), and blood volume (p= 0.013). A significant increase was observed in oxyhemoglobin, blood volume, and oxygenation compared to pre-cupping (p< 0.05) in the area outside the cup. CONCLUSION: Our findings indicate that an appropriate combination of cupping pressure and duration can effectively affect the spatial hemodynamic response of the biceps.

Hemoglobina Denver, una causa de desaturación en oximetría de pulso. Reporte de caso en un paciente pediátrico / Hemoglobin Denver, a cause of desaturated pulse oximetry. A pediatric case report

Las hemoglobinopatías son trastornos genéticos que afectan a la molécula de hemoglobina (Hb). Las mutaciones en las cadenas a o b que alteran el tetrámero de Hb pueden modificar la capacidad de la molécula para unirse al oxígeno. Las hemoglobinopatías con baja afinidad al oxígeno pueden presentarse con cianosis y una lectura alterada de la oximetría de pulso, lo que lleva a pruebas innecesarias y, a veces, invasivas para descartar afecciones cardiovasculares y respiratorias. En el siguiente reporte de caso, presentamos a una paciente pediátrica, asintomática, que se presentó a la consulta por detección de desaturación en oximetría de pulso. Las pruebas de laboratorio iniciales mostraron una anemia normocítica, normocrómica. Las muestras de gas venoso demostraron una p50 elevada. Después de extensas herramientas de diagnóstico, se diagnosticó una variante de Hb con baja afinidad al oxígeno, Hb Denver.

Hemoglobinopathies are genetic disorders that affect the hemoglobin (Hb) molecule. Mutations in the alpha or beta chains altering the Hb tetramer may modify the molecule's oxygen-binding capacity. Hemoglobinopathies with low oxygen affinity may occur with cyanosis and an altered pulse oximetry reading, leading to unnecessary and sometimes invasive tests to rule out cardiovascular and respiratory conditions. In the case report described here, we present an asymptomatic pediatric patient who consulted for desaturated pulse oximetry. Her initial laboratory tests showed normocytic, normochromic anemia. Venous blood gas samples showed an elevated p50. After using extensive diagnostic tools, a variant of Hb with low oxygen affinity was diagnosed: Hb Denver.

Are sex differences in blood cell count and hemoglobin moderated by the 2D:4D ratio? A cross-sectional study in a Ghanaian population.

Background and Aims: There are sex differences in blood cell count and hemoglobin (HGB) in adulthood due to differences in the levels of circulating sex hormones. The second-to-fourth digit ratio (2D:4D) is the putative marker of prenatal hormone exposure. The 2D:4D or the right-left difference (Dr-l) are sexually dimorphic and are correlates of sex hormones in adulthood. The study sought to determine whether sex differences in adult blood cell count and HGB can be partly explained by the 2D:4D or Dr-l. Methods: The study was cross-sectional between June and December 2021 at the University for Development Studies. The study involved 207 healthy participants (females = 113) aged from 18 to 32 years. The right-hand (2D:4DR), and the left-hand (2D:4DL) digit ratio and their difference (Dr-l) were measured using Computer-assisted analysis. Blood cell count, HGB, testosterone, and estradiol were measured from venous blood samples using an automated HGB analyzer and ELIZA technique. Results: The platelet count was inversely related to the 2D:4DR in the total sample with the 2D:4DR accounting for about 0.2% (adjR 2 = 0.002) of the variability in platelet count. However, there was a sex difference as indicated by the significant interaction between sex and the 2D:4DR on platelet count (p = 0.03). The relationship between platelet count and the 2D:4DR was negative in females but positive in males. Also, there was a positive relationship between HGB concentration and the Dr-l in the total study sample, where the Dr-l accounted for about 0.6% (adjR 2 = 0.006) of the variability in HGB concentration. Sex interacted significantly with the Dr-l on HGB concentration (p = 0.01) such that the relationship between HGB and the Dr-l was positive in females but negative in males. Conclusion: Prenatal hormone exposure, as indexed by the 2D:4D ratio, may partly account for the observed sex differences in platelet count and HGB levels in adulthood.

Clinicopathological significance of vasculogenic mimicry and fetal hemoglobin expression in peripheral neuroblastic tumors in children.

PURPOSE: Vasculogenic mimicry (VM) is present in a variety of malignant tumors, and is related to the degree of malignancy. Neuroblastoma (NB) can induce the expression of fetal hemoglobin (HB-F). The purpose of this study was to investigate the clinicopathological significance of the number of VMs and tumor cell expression of HB-F in children with peripheral neuroblastic tumors (pNTs). MATERIALS AND METHODS: We collected tissue samples and clinical data from 101 children with pNTs; prepared serial sections of tissue wax blocks for hematoxylin and eosin staining, CD31/periodic acid-Schiff double staining, and HB-F immunohistochemical staining; and analyzed the experimental results. RESULTS: There were significant differences in the number of VMs and HB-F expression in tumor cells according to the pathological classification of pNTs (P<0.001, collectively). Poorly differentiated NB had a median of 137 VMs and 25.5% HB-F expression. Differentiating NB had a median of 90.5 VMs and 8.5% HB-F expression. Ganglioneuroblastoma intermixed had a median of 6.0 VMs and 1.0% HB-F expression. Ganglioneuromas had no VM and a median of 0% HB-F expression. The number of VMs and the expression of HB-F were significantly higher in the poor prognosis group than the good prognosis group (P<0.001, collectively). There was a strong positive correlation between the number of VMs and HB-F expression in pNTs (r=0.891, P<0.001). CONCLUSION: We confirmed VM and HB-F expression in pNTs. The number of VMs and HB-F expression were higher in poorly differentiated tumors. The number of VMs and level of HB-F expression in pNTs might be related to the prognosis.

Relación del equivalente de hemoglobina reticulocitaria (Ret-He) con diferentes categorías según la concentración de hemoglobina en candidatos a donar sangre

Objetivo: determinar la relación entre el Ret-He con diferentes categorías según la concentración de hemoglobina en candidatos a donar sangre. Materiales y Métodos: Se realizó un estudio transversal a partir de la revisión de 227 historias clínicas de candidatos a donar sangre durante el mes de diciembre del 2021 en el Servicio de Banco de Sangre y Hemoterapia del Hospital Cayetano Heredia. Se categorizó en 3 grupos según los niveles de hemoglobina: Grupo 1: ≥12,5 g/dl (mujeres) - ≥13,5 g/dl (varones). Grupo 2: 12 g/dl ≥ mujeres <12.5 g/dl y 13 g/dl ≥ varones<13.5 g/dl. Grupo 3: <12 g/dl (mujeres) - <13 g/dl (varones). Se tomaron datos de hematocrito, hemoglobina, VCM, HCM, CHCM y Ret-He. Para el análisis bivariado se utilizó el análisis de varianza (ANOVA) y se consideró un nivel de significancia del 5 %. Resultados: La mediana de Ret-He fue mayor en el grupo 1 que en el grupo 2 (33.5 frente a 32.5; p=0.002) y en el grupo 3 (33.5 frente a 27.8; p<0.001). Se encontró relación estadísticamente significativa entre los grupos estudiados y Ret-He (p<0.001), además de una correlación positiva moderada fuerte entre Ret-He y los índices eritrocitarios. Conclusiones: Se encontró una asociación significativa entre los grupos basados en categorías de hemoglobina y la Ret-He en candidatos a donar sangre.

Objective: to determine the relationship between Ret-He with different categories according to hemoglobin concentration in candidates for blood donation. Methods: A cross-sectional study was carried out based on the review of 227 medical records of candidates to donate blood during the month of December 2021 in the Blood Bank and Hemotherapy Service of the Cayetano Heredia Hospital. They were categorized into 3 groups according to hemoglobin levels: Group 1: ≥12.5 g/dl (females) - ≥13.5 g/dl (males). Group 2: 12 g/dl ≥ females <12.5 g/dl and 13 g/dl ≥ males<13.5 g/dl. Group 3: <12 g/dl (females) - <13 g/dl (males). Hematocrit, hemoglobin, VCM, HCM, CHCM and Ret-He data were collected. For the bivariate analysis, analysis of variance (ANOVA) was used and a significance level of 5% was considered. Results: The median Ret-He was higher in group 1 than in group 2 (33.5 vs. 32.5; p=0.002) and in group 3 (33.5 vs. 27.8; p<0.001). A statistically significant relationship was found between the groups studied and Ret-He (p<0.001), in addition to a moderate-strong positive correlation between Ret-He and erythrocyte indices. Conclusions: An association was found between groups based on hemoglobin categories and Ret-He in blood donation candidates.

Structural and dynamic characterization of the hexa-coordinated globin from Spisula solidissima.

High energy consumption in the nervous system requires a continuous supply of O2. This role is assisted by proteins from the globin super-family in the nerve cells of invertebrates, where 'nerve hemoglobins' (nHbs) are mainly present at mM concentrations and exhibit oxygen affinities comparable to those of vertebrate myoglobins. To gain insight into the structural bases of this function, we report the crystal structure of nHb from the Atlantic surf clam Spisula solidissima (SsHb), previously suggested to display a bis-histidyl hexa-coordinated heme in the deoxy state, high O2 affinity, and ligand binding cooperativity when assayed in situ. The crystallized protein forms a dimer through packing of a 4-helix bundle involving helices E and F of each subunit. The SsHb 'classic' globin fold displays bis-histidyl (His71(E7) and His103(F8)) hexa-coordination of the heme-Fe atom, with structural and dynamics variations found in the inter-helix hinge regions. Molecular Dynamics simulations of both monomeric and dimeric species in the bis-histidyl hexa-coordinated, deoxy penta-coordinated, and O2-bound hexa-coordinated states reveal distinct structural rearrangements at the interface between subunits in the dimer; these would affect the magnitude of the conformational fluctuations observed between monomer and dimer, and the topology of cavities within the protein matrix and at the interface. These results point to a distal site opening mechanism allowing access of the exogenous ligand to the heme and cast hypotheses on the dimer interface structural and dynamic properties that may support ligand binding cooperativity in dimeric SsHb.

Efficacy of needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3) on cerebral cortical blood oxygen level in rats with insomnia.

OBJECTIVE: To evaluate the effect of needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3) on cerebral cortical blood oxygen level in rats with insomnia identified as liver- stagnation pattern in terms of Traditional Chinese Medicine. METHODS: Sixty Wistar rats were randomly divided into blank group ( 10), the rest of the rats were clamped tail as stimulation combined with injected intraperitoneally p-chlorophenylalanine (PCPA) to establish sleep deprivation model. After the successful replication of the model, they were randomly divided into model group, grabbing group, Western Medicine group, acupuncture group and sham acupuncture group, with 10 rats in each group. The model group was given normal saline; The grasping group was grasped in the same way as the two treatment groups; Western medicine group was given estazolam solution; The acupuncture group was treated with the acupuncture method of "soothing the liver and regulating mind" needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3); The sham acupuncture group were needled with four non-acupoint sites. After 7 d of treatment of rats in each group, sodium pentobarbital sleep experiment was used to evaluate the sleep latency (SL) and sleep time (ST). The percentage of rats entering the open arm (OE%) and the percentage of time entering the open arm (OT%) in each group were monitored by elevated cross maze, and the vertical score, horizontal crossing times, central grid score and modification times were monitored by open field test, functional near infrared spectroscopy (fNIRs) was used to monitor the changes of oxygenated hemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb) and total hemoglobin (Total-Hb) in the cerebral cortex of rats in each group under light stimulation and dark stimulation, the statistically significant channel combinations were selected from 8 light sources and 12 detectors (S-D). According to the position of the light source detector covering the cerebral cortex, Preliminarily determine the key brain areas of insomnia (the preliminary experiment found that 6S-8D and 7S-9D were the key channels of insomnia under light stimulation, and the corresponding brain areas were prefrontal lobe and occipital lobe respectively; 7S-7D channel under dark stimulation, and the corresponding brain area was occipital lobe); The hemodynamic map of cerebral cortex was constructed through the absolute value of whole brain blood oxygen level. Further identify key brain regions for insomnia. RESULTS: Compared with the blank group, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score, the concentration of Deoxy-Hb in prefrontal and occipital lobes were decreased significantly (<0.01), and the concentrations of SL, modification times, Oxy-Hb and Total-Hb were increased significantly (<0.01); There was no difference in the above indexes between the model group and the grabbing group (>0.05); After treatment, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score and Deoxy-Hb concentration in acupuncture group and Western medicine group increased significantly, while SL, modification times, Oxy-Hb and Total-Hb concentrations were decreased significantly (<0.01, <0.05), Compared with the Western Medicine group, the values of OE% and OT% were more significantly higher in the acupuncture group (<0.05), while the rest of the indexes were not significantly different between the two groups (>0.05); Compared with the acupuncture group, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score and the concentration of deoxy Hb in the sham acupuncture group decreased significantly (<0.01), and the concentrations of SL, modification times, Oxy-Hb and Total-Hb increased significantly (<0.01). CONCLUSIONS: The needling method for soothing the liver and regulating mind could improve the abnormal behavior of insomnia rats with liver stagnation, and its effect on the improvement of abnormal mood caused by insomnia with liver stagnation is better than that of Western Medicine, and the mechanism of action may be related to the regulation of blood oxygen metabolism in the prefrontal and occipital lobes of the cerebral cortex by acupuncture.

Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body's first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin's anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Evaluation of the effect of preoperative rectal misoprostol use on the postoperative outcomes of hysteroscopic myomectomy.

AIM: In this study, we aimed to evaluate the effect of using two doses of rectal misoprostol on postoperative results in hysteroscopic myomectomy. METHODS: This retrospective study was carried out at two hospitals in which the medical records of patients who underwent hysteroscopic myomectomy between November 2017 and April 2022 were evaluated, and subjects were grouped depending on the administration of misoprostol before hysteroscopy. In recipients, two rectal doses of misoprostol (400 µg) were administered, 12 h and 1 h before the planned operation. Outcomes evaluated were: postoperative reduction in hemoglobin (Hb), pain at 12 and 24 h (VAS score), and length of hospital stay. RESULTS: The mean age of 47 women in the study group was 27.38 ± 5.12 (range 20-38) years. Hb levels reduced significantly in both groups after hysteroscopic myomectomy (p < 0.001). In misoprostol recipients, VAS score was found to be significantly lower at 12 h (p < 0.001) and 24 h after the operation (p = 0.004). Multiple linear regression analyses for each of the outcomes revealed the following: greater myoma size was associated with greater Hb decrease (p = 0.010), misoprostol use was associated with lower 12th and 24th hour VAS scores (p < 0.001), longer duration of operation was associated with higher 12th and 24th hour VAS scores (p < 0.001), and finally, longer duration of operation was associated with prolonged hospital stay (p = 0.001). CONCLUSIONS: The use of two doses of rectal misoprostol before hysteroscopic myomectomy was effective in reducing postoperative pain. Prospective, population-based studies evaluating different uses of misoprostol in hysteroscopic myomectomy are needed.