Abnormal Band Research Articles

Comorbidity of concussion and depression alters brain functional connectivity in collegiate student-athletes

Depression and concussion are highly prevalent neuropsychological disorders that often occur simultaneously. However, due to the high degree of symptom overlap between the two events, including but not limited to headache, sleep disturbances, appetite changes, fatigue, and difficulty concentrating, they may be treated in isolation. Thus, clinical awareness of additive symptom load may be missed. This study measures neuropsychological and electroencephalography (EEG) alpha band coherence differences in collegiate student-athletes with history of comorbid depression and concussion, in comparison to those with a single morbidity and healthy controls (HC). 35 collegiate athletes completed neuropsychological screenings and EEG measures. Participants were grouped by concussion and depression history. Differences in alpha band coherence were calculated using two-way ANOVA with post hoc correction for multiple comparisons. Comorbid participants scored significantly worse on neuropsychological screening, BDI-FS, and PCSS than those with a single morbidity and HC. Two-way ANOVA by group revealed significant main effects of alpha band coherence for concussion, depression, and their interaction term. Post-hoc analysis showed that comorbid participants had more abnormal alpha band coherence than single morbidity, when compared to HC. Comorbidity of concussion and depression increased symptom reporting and revealed more altered alpha band coherence than single morbidity, compared to HC. The abnormalities of the comorbid group exclusively showed decreased alpha band coherence in comparison to healthy controls. The comorbidity of depression and SRC has a compounding effect on depression symptoms, post-concussion symptoms, and brain functional connectivity. This research demonstrates a promising objective measure in comorbid individuals, previously only measured via subjective symptom reporting.

Proton Transfer Processes in 2-Butenenitrile Dimer Cation Studied by Mass-Selective Infrared Spectroscopy.

2-Butenenitrile (2-Bu) is a recently discovered crucial interstellar molecule. Herein, an abnormal NH band was observed in the infrared spectrum of the 2-Bu dimer cation, suggestive of a proton transfer reaction within the cluster. Through a comprehensive theoretical analysis of the IR spectrum of (2-Bu)2+, we discovered not only the formation of a new C-N bond through the attachment of one 2-Bu to another but also the occurrence of a proton transfer reaction in the cluster. This proton was identified as originating from the methyl group of the attaching 2-Bu in the cluster based on the analysis of IR spectra of (2-Bu)+ and [2-Bu-acrylonitrile (AN)]+. Furthermore, the detailed reaction process of this ion-molecule reaction is examined with theoretical calculation. This finding contributes significantly to our deeper understanding of ion-molecule reactions in the gas phase and the formation of nitrogen-containing prebiotic molecules in the interstellar medium.

Analysis of abnormal bright band characteristics of forging for a new low-cost titanium alloy

A centimeter-scale defective microstructure, namely abnormal bright band characteristics (ABBC), is found in engineering production of titanium alloy forgings, and it seriously affects the stability and reliability of performance. The targeted work for the reason of the formation of the ABBC is carried out in this paper. The ABBC contains a large number of small colony α, without grain boundary. The α phase in the ABBC includes 12 variants from one β grain. The crystallographic orientation of reconstructed β phase in the ABBC is a standard cube texture. The formation of the ABBC is caused by the abnormal grain growth (AGG) of cube-grain. The cube-grain is a low energy storage grain, which can merge with other grains to grow rapidly.

Molecular characterization of similar Hb Lepore Boston-Washington in four Chinese families using third generation sequencing.

Hemoglobin (Hb) Lepore is a rare deletional δβ-thalassemia caused by the fusion between delta-beta genes, and cannot be identified by traditional thaltassemia gene testing technology. The aim of this study was to conduct molecular diagnosis and clinical analysis of Hb Lepore in four unrelated Chinese families using third generation sequencing. Decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and an abnormal Hb band were observed in the probands of the four families. However, no common α and β-thalassemia variants were detected in the enrolled families using polymerase chain reaction-reverse dot blot hybridization based traditional thalassemia gene testing. Further third-generation sequencing revealed similar Hb Lepore-Boston-Washington variants in all the patients, which were resulted from partial coverage of the HBB and HBD globin genes, leading to the formation of a delta-beta fusion gene. Specific gap-PCR and Sanger sequencing confirmed that all the patients carried a similar Hb Lepore-Boston-Washington heterozygote. In addition, decreased levels of MCH and Hb A2 were observed in the proband's wife of family 2, an extremely rare variant of Hb Nanchang (GGT > AGT) (HBA2:c.46G > A) was identified by third-generation sequencing and further confirmed by Sanger sequencing. This present study was the first to report the similar Hb Lepore-Boston-Washington in Chinese population. By combining the utilization of Hb capillary electrophoresis and third-generation sequencing, the screening and diagnosis of Hb Lepore can be effectively enhanced.

Ultra-Broadband Plasmon Resonance in Gold Nanoparticles Precipitated in ZnO-Al2O3-SiO2 Glass

Optical materials with a tunable localized surface plasmon resonance (LSPR) are of great interest for applications in photonics and optoelectronics. In the present study, we explored the potential of generating an LSPR band with an ultra-broad range of over 1000 nm in gold nanoparticles (NPs), precipitated through a thermal treatment in ZnO-Al2O3-SiO2 glass. Using optical absorption spectroscopy, we demonstrated that the LSPR band’s position and shape can be finely controlled by varying the thermal treatment route. Comprehensive methods including Raman spectroscopy, X-ray diffraction, and high-resolution transmission electron microscopy were used to study the glass structure, while computational approaches were used for the theoretical description of the absorption spectra. The obtained results allowed us to suggest a scenario responsible for an abnormal LSPR band broadening that includes a possible interparticle plasmonic coupling effect taking place during the liquid–liquid phase separation of the heat-treated glass. The formation of gold NPs with an ultra-broad LSPR band in glasses holds promise for sensitizing rare earth ion luminescence for new photonics devices.

An up-conversion fluorescence lateral-flow immunoassay for rapid detection of Daratumumab in serum protein electrophoresis clinical samples

BackgroundDaratumumab (DARA) is a commonly used monoclonal antibody (mAb) drug for the treatment of multiple myeloma (MM). Its appearance as a visible abnormal band in the γ-region of a serum protein electrophoresis (SPEP) gel may interfere with the SPEP result interpretation. With the advantages of portability and rapid testing capabilities, up-conversion fluorescence lateral-flow immunoassay (LFA) can be an ideal solution to detect DARA interference. MethodsAn up-conversion fluorescence LFA strip was designed and constructed to perform semi-quantitative DARA testing in clinical samples. The LFA strip test was evaluated for limit of detection (LOD), dynamic range, and analytical interference. ResultsTo demonstrate the clinical utility of the LFA strip, 43 SPEP-positive patient serum samples were tested for the presence of DARA, and the results exactly matched the DARA usage history in patient medical records. ConclusionsThe performance of the up-conversion fluorescence LFA strip meets the purpose of clarifying DARA interference in SPEP results. It may be used as an independent and objective confirmation of the presence of DARA in clinical samples. The LFA strip offers a cost-effective rapid on-site test to check for DARA interference alongside standard SPEP equipment, which significantly improves the interpretation of ambiguous SPEP results involving DARA, and does not intervene the current SPEP workflow in clinical laboratory practice.

A Case of Lymphoplasmacytic Cell Lymphoma Characterized by Marked Nuclear Fission and Brain Gyrus Nuclei of Lymphocytes

A 67-year-old male was admitted to the hospital due to fatigue and thrombocytopenia. Peripheral blood cells analysis showed the white blood cells count of 2.99 × 109 /L, red blood cell (RBC) count of 2.08 × 1012/L, platelet count of 15 × 109 /L. β2- microglobulin of serum was 5.50 mg/L. Whole-body positron emission tomography-computed tomography suggested altered reactivity in the lymph nodes of the bilateral neck. Morphological examination of bone marrow (BM) indicated the presence of abnormal smaller lymphocytes, accounting for 12.5% of the total nucleated cells. Strikingly, nuclear fission or brain gyrus nuclei were prominently observed in all abnormal lymphocytes (Figure 1, original magnification 1000×; Wright–Giemsa stain). The proportion of plasma cells was 0.5%, and no morphological abnormalities were observed. Additionally, some RBCs were exhibited a rouleaux arrangement. Flow cytometry analysis of BM identified 16.12% of κ-restricted B lymphocytes expressing CD5- , CD10- , CD19+ , CD20+ . A minimal proportion of 0.03% plasma cells with κ/λ ratio of 1.07. Consistent results were confirmed by immunohistochemistry in the BM biopsy. Immunofixation electrophoresis revealed abnormal monoclonal bands in the IgM and κ lanes. Furthermore, mutations of MYD88 (L265P), CXCR4 (T318fs), and TP53 (R306X) were identified through next-generation sequencing analysis. A diagnosis of lymphoplasmic cell lymphoma/waldenström macroglobulinemia (LPL/WM) was established.

Chemical Vapor Deposition Growth of Atomically Thin SnSb2Te4 Single Crystals Toward Fast Photodetection

AbstractSnSb2Te4 (SST), a ternary van der Waals (vdW) material, has been widely investigated during last decades for potential applications in superconductivity, thermoelectricity, and optoelectronics. Recently, atomically thin SST has been predicted to show abnormal electronic band structure evolutions, high carrier mobility, and strong light–matter interaction. However, controllable synthesis of such SST crystals has been a huge challenge. Herein, atomically thin SST flakes are prepared via a chemical vapor deposition (CVD) method by using SbCl3, SnCl4·5H2O, and Te as the precursors. Multiple structural characterizations reveal that the SST flakes are single crystals with high crystallinity. Due to the narrow bandgap of 0.42 eV, SST‐based photodetectors have a broadband spectrum detection range from visible light through communication bands (480–1550 nm). More importantly, benefiting from a high room‐temperature carrier mobility over 300 cm2 V−1 s−1, the SST photodetectors demonstrate a response/recovery time of tens of tens of microseconds, which exceeds most typical transition metal dichalcogenide (TMDC) flakes. In addition, the photodetector maintains high performance after being exposed to the air for 2 months, suggesting good environmental stability. These excellent performances suggest that the SST flakes are promising for next‐generation optoelectronics.

Abstract P05: Testing patterns and referrals for monoclonal protein detection at John Peter Smith hospital

Abstract Background: Multiple myeloma (MM) is an incurable disease. Blacks have a higher incidence of MM and are diagnosed at a younger age compared to other populations. Safety-net hospitals (SNH) treat a high proportion of Black patients. Early detection of myeloma is important to prevent permanent organ dysfunction. Serum monoclonal protein testing using expanded panel aids in the diagnosis and monitoring of monoclonal gammopathies. This test result has 16 discrete components and any out-of-range value can be confusing to the ordering providers, triggering referrals to hematology oncology (hemonc). We sought to identify the testing and referral patterns at John Peter Smith (JPS) Hospital, a SNH in North Texas. Methods: Data was obtained from JPS Data Analytics and Reporting department. All serum monoclonal protein expanded panel (LAB174) orders and results for patients tested from 1-1-2022 to 12-31-2022 were abstracted from EPIC EMR. Demographic information was collected along with details about ordering providers and referrals. We sorted the data and excluded all orders by oncology providers as well as all inpatient orders. Data analysis was completed using Excel. Results: A total of 1063 tests were performed on 1026 patients. 39% were Non-Hispanic White (NHW), 36% were Black, and 13% were Hispanic. Median age was 57 years. Monoclonal band was seen in 143 (13%) samples; immunoglobulin (IG) kappa (k) 59, IG lambda (λ) 68, both IG k and IG λ 9. Results with gamma (γ) and beta (β) band were seen in 22 and 3 respectively. Measurable k band (>0.1 g/dL) was seen in 12 tests, > 1 g/dL in 5, and > 3 g/dL in only 1 test. Measurable λ band seen in 9 tests, > 1 g/dL in 3, and > 3 g/dL in no tests. Serum protein electrophoresis (SPEP) was normal in 525, and immunofixation (IFE) was normal in 507. Polyclonal SPEP was noted in 169 tests. Hypogammaglobinemia was seen in 11. 72 out of 369 (20%) Blacks had abnormal bands vs 47 out of 397 (12%) NHW. Two-tailed t-test was significant at p-value 0.00327. Referrals were generated to hemonc in 201 patients. Rheumatology accounted for 19% of tests, nephrology 18%, neurology 19%, and remaining were from primary care and other specialties. 212 patients were referred to hematology oncology using ICD10 diagnosis code R77.8. Rheumatologists referred 48 patients, which is 25% of all patients that they tested. Referrals from neurology: 39 (20%) and nephrology: 25 (13%). Conclusions: At JPS, clinical care providers are conducting tests to identify precursor conditions to myeloma. The test positivity rate was 13% in the non-oncology outpatient setting. Blacks had a higher percentage of positivity, reinforcing the need for a higher index of suspicion. The complexity of the test results, however, is overwhelming to the ordering providers, triggering referrals to the hemonc division, prompting recruitment and training of midlevel providers within hemonc to ensure proper monitoring of patients with precursor conditions. JPS Office of Clinical Research is planning to participate in early detection clinical trials for myeloma. Citation Format: Kavya Athipatla, Melissa Howell, Anuradha Lingam, Kayani Narra. Testing patterns and referrals for monoclonal protein detection at John Peter Smith hospital [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P05.

Effect of shot speeds on the microstructural framework and abnormal eutectic bands in a high pressure die casting hypoeutectic AlSi10MnMg alloy

The microstructural framework of a high-pressure die-cast hypoeutectic AlSi10MnMg alloy and the formation mechanism of two type abnormal eutectic bands under varied die casting shot speeds are proposed. Before the eutectic band zone solidifies, the central external solidified crystals (ESCs) dendrite-enriched zone and surface chilling zone have been developed. The residual Si-rich melt stars to solidify from surface to center along the formed feeding path of framework. In addition, liquid filling speed in high pressure die casting (HPDC) will not alter the sequential solidification sequence but affect the formation of eutectic band. The high-speed liquid flow causes relatively dispersive ESCs from surface to center while low-speed liquid flow accelerates the migration of ESCs to center and thus causes the formation of a larger dendritic network which is decisive to the different formation mechanism of eutectic bands. Eutectic band position before solidification serving as an interface between solidified zone and central dendritic network exhibits the characteristics of a higher velocity melt flow, a lower solid fraction and a fewer ESCs content. This study provides insights into near-rapid solidified behavior combining liquid filling process and it is expected to expand the conception to other die cast alloys.

Abnormal lesion that can be confused with medial meniscal tears, medial meniscocapsular band: a rare presentation

This case report describes a medial meniscocapsular band, a structure extending from the medial capsule of the knee joint to the corpus of the medial meniscus, observed during arthroscopy in a 48-year-old woman. Preoperative physical examination findings were compatible with medial meniscal pathology only; magnetic resonance imaging showed an abnormal medial meniscus and was interpreted in favor of a tear. Arthroscopic examination showed an abnormal band inside the knee. This anatomical lesion is quite rare and similar lesions have been reported in the literature, but the extension of the band in our case is different from the extension in the cases seen in the literature. We believe that the identification of abnormal meniscal types or intra-articular bands is necessary to provide greater accuracy in MR imaging reporting.

Third-generation sequencing identified two rare α-chain variants leading to hemoglobin variants in Chinese population.

Rare and novel variants of HBA1/2 and HBB genes resulting in thalassemia and hemoglobin (Hb) variants have been increasingly identified. Our goal was to identify two rare Hb variants in Chinese population using third-generation sequencing (TGS) technology. Enrolled in this study were two Chinese families from Fujian Province. Hematological screening was conducted using routine blood analysis and Hb capillary electrophoresis analysis. Routine thalassemia gene testing was carried out to detect the common mutations of α- and β-thalassemia in Chinese population. Rare or novel α- and β-globin gene variants were further investigated by TGS. The proband of family 1 was a female aged 32, with decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), Hb A2, and abnormal Hb bands in zone 5 and zone 12. No common thalassemia mutations were detected by routine thalassemia analysis, while a rare α-globin gene variant Hb Jilin [α139(HC1)Lys>Gln (AAA>CAA); HBA2:c.418A>C] was identified by TGS. Subsequent pedigree analysis showed that the proband's son also harbored the Hb Jilin variant with slightly low levels of MCH, Hb A2, and abnormal Hb bands. The proband of family 2 was a male at 41 years of age, exhibiting normal MCV and MCH, but a low level of Hb A2 and an abnormal Hb band in zone 12 without any common α- and β-thalassemia mutations. The subsequent TGS detection demonstrated a rare Hb Beijing [α16(A14)Lys>Asn (AAG>AAT); HBA2:c.51G>T] variant in HBA2 gene. In this study, for the first time, we present two rare Hb variants of Hb Jilin and Hb Beijing in Fujian Province, Southeast China, using TGS technology.

Identification of Novel Hb Guiyang [HBA2: c.151C > A α2 50 (CE8) His- Asn] and Phenotype- Genotype Correlation of Abnormal Hemoglobins in Guizhou, Southwest China.

To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and β - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and β globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

Reporting Practices of Serum Protein Electrophoresis in Pakistan - a Multicenter Survey.

Serum Protein Electrophoresis (SPE) is crucial for the diagnosis and follow-up of monoclonal gammopathy (MG), as it helps to separate and identify these paraproteins. Currently, Pakistan lacks standardized guidelines for SPE reporting and analytical performance. This survey aims to analyze reporting variations from Consultant Chemical Pathologists in Pakistani laboratories. This cross-sectional survey was conducted by the section of Chemical Pathology, Department of Pathology and Laboratory Medicine, at Aga Khan University Hospital, Karachi. A previously validated and published tool was used with some modifications to assess analytical techniques, reporting patterns, and interpretations provided with SPE by different laboratories. Frequency and percentages were calculated for each response and descriptive results were also evaluated. Differences between laboratories were also assessed qualitatively. Out of the eight laboratories contacted, seven participated in the survey, yielding a response rate of 87.5%. Immunofixation Electrophoresis (IFE) was used by all labs for serum immunotyping. All labs reported a new small abnormal band in patients with no known monoclonal gammopathy or with a known M-protein. Variations were found in terminologies used to label paraprotein, terminologies used to report normal and pathological SPE patterns, electrophoretic technique, methods for quantifying paraprotein in the gamma region on SPE and for albumin quantification. Similarly, the number of decimal places reported, reporting of multiple monoclonal proteins and small paraprotein in the beta region or monoclonal proteins less than 1 g/L, approach for screening, number of fractions reported in gamma region and reporting of interferences were also not standardized and var-iations were noticed. Our survey highlighted variations in practices of SPE reporting. These differences in laboratory practices could result in inconsistent test results, which could adversely affect patient care.

Prevalence of myocardial bridges in the Mexican population: A morphometric and histological analysis

Myocardial bridge (MB) is described as an abnormal band of myocardium covering a variable portion of any coronary artery. The current study explores the presence of MB throughout the coronary arterial system and provides a morphometric description through instrumented dissection of a sample of 100 human hearts. The study shows a higher prevalence of MB in the Mexican population than in previous reports. In the total sample (n=100), MB was identified in 96% of it. A total of 421 MBs were observed, with a mean of 4.38mm (±0.28) per dissected heart. The most frequently affected vessel is the anterior interventricular artery where a total of 52 MBs were found, of the total sample studied. The high prevalence of MB among Mexican patients could be the result of a genetic association for this population or the neoformation of MB after birth due to lifestyle-associated factors. Further studies are required to better understand the high prevalence of MB among Mexican subjects.

How Do Event‐Related Gamma Oscillations Differ in Alzheimer’s Disease From Other Types of Dementia ?

AbstractBackgroundAlthough recent studies showed that gamma frequency entrainment might have therapeutic effects on Alzheimer’s Disease (AD) (Iaccarino et al. 2016), the gamma band abnormalities in AD patients are still poorly understood, while some studies presented increased gamma responses in AD, others showed reduced gamma responses (Güntekin et al., 2022). The differentiation of gamma responses between different dementia types is also not known. The present study aims to analyze the event‐related gamma responses in AD patients and to find out how the event‐related gamma responses differentiate between AD, Parkinson’s disease dementia (PDD), and Lewy Body dementia (DLB).MethodEEG of 17 DLB, 19 PDD, 20 AD patients, and 20 healthy controls was recorded with a 32‐channel EEG device. Subjects had performed visual oddball paradigm during EEG recordings. Event‐related phase locking and Event‐related power were analyzed in three gamma frequency bands (25‐30 Hz, 30‐35 Hz, 35‐48 Hz) in three different time windows (0 200 ms, 200 400 ms, 400‐600 ms) for target and non‐target stimuli. Repeated measures of ANOVA were used with the between‐subjects and within‐subjects factors.ResultTarget responses elicited higher gamma phase locking than the non‐target responses (p<0.05). Healthy subjects had higher gamma phase locking than AD, PDD, and DLB patients (p<0.05). The healthy control group had increased gamma power in the 0‐200 ms time window at frontal and central locations (p<0.05); however, patient groups did not have this early time window increase of gamma responses. Furthermore, although it was non‐significant, gamma phase locking values of PDD and DLB patients were worse than AD.ConclusionThe present study showed that AD, PDD, and DLB patients had reduced event‐related gamma phase locking and power in the early time window compared to healthy elderly controls. The gamma phase locking values of PDD and DLB patients were worse than those of AD patients. The present study showed that similar to AD patients and other dementia types could also have deficits in the gamma frequency band. Since the PDD and DLB patients had even more abnormal gamma band activities, the gamma entrainment could also have positive effects in these groups of patients.

Rare Sighting of an Unstable Hemoglobin Variant [ Β11 (A8) Val → Asp]: Hemoglobin Windsor

Hemoglobin (Hb) is the major blood oxygen carrier where Hb subunits bind oxygen via the heme iron buried within a hydrophobic pocket that faces the outside of HbA tetramers. Iron must be in its reduced (ferrous, Fe2+) state for Hb to bind oxygen. Oxidized or metHb (ferric, Fe3+) cannot bind oxygen and is relatively unstable. Globin mutations that alter amino acids within the ligand pocket lead to changes in affinity for oxygen, and increased rates of metHb formation and heme loss. We present the case of a patient with a rare variant “Hb Windsor” which has only been described once in the literature. The patient is a 20-year-old Mexican male with a history of hepatitis B presenting with three days of fevers, chills, nausea and vomiting. The patient reported a diagnosis of hepatitis at the age of eight in Mexico and with jaundice all his life. He had no prior hospitalizations or blood transfusions. He denied any unusual food ingestions or recent foreign travel. In the emergency room, the patient was hypoxic with a SpO2 73% and tachypneic which improved with supplemental oxygen. On physical examination, the patient was jaundiced with scleral icterus and the spleen was easily palpable to the midline. CT scan confirmed splenomegaly measuring 20 cm. Labs showed a white blood count 21.6 nl, hemoglobin 4.2 g/dl, platelet count 33 nl, lactate dehydrogenase 13 unit/L and reticulocyte count 24%, total bilirubin 16 mg/dl, direct bilirubin 4 mg/dl and methemoglobin 20.9%. The patient was administered methylene blue and transfused two units of packed red blood cells with hemoglobin increasing to 7.1 g/dl. HIV, hepatitis B and C, direct antiglobulin test, and G6PD testing were negative. The peripheral smear showed numerous nucleated red cells, increased polychromasia with red cells showing numerous microspherocytes, microanthocytes, and bubbled cells with significant basophilic stippling. No fragmented cells were present. The clinical history and lab findings suggested a chronic hemolytic anemia, and the peripheral smear suggested a possible hemoglobinopathy. Hemoglobin electrophoresis by high performance liquid chromatography showed an unknown hemoglobin of 22.5%. Isoelectric focusing showed Hb A 71.9%, F, Hb A2 4.6%, Hb F 0.3%, and an abnormal band of 23% in the hemoglobin M range. Specimens were sent for DNA sequencing and a point mutation in the beta chain was found leading to a valine to aspartate substitution in the A8 position. Protein analysis showed a valine is substituted with aspartic acid in the ligand pocket which is the unstable varian Hb Windsor. This substitution in the base of the heme pocket results in instability of the hemoglobin molecule and an increase in oxygen affinity. The residues lining the heme pocket function as a hydrophobic basket from the heme iron, preventing its oxidation to the ferric state. Valine, which occupies position A8 is a hydrophobic amino acid. However, in Hb Windsor, the valine is substituted by aspartic acid, a polar molecule. The hydrophilic nature of aspartic acid, a polar molecule, may disrupt the hydrophobic nature of the heme pocket. The valine at position A8 also acts as a contact with the H helix which is lost in Hb Windsor leading to decreased Hb stability. These substitutions cause heme iron to auto-oxidize which results in methemoglobinemia. Hb M has iron in the ferric state (Fe3+) and is unable to carry oxygen which produces cyanosis. Our patient was found to be hypoxic requiring oxygen supplementation and found to have methemoglobinemia. We present a rare case of a hemoglobin variant Hb Windsor in a Mexican adult which has only been previously documented in a nine-month-old Anglo-Saxon infant. This variant seems to be a spontaneous de novo mutation as both patients had no family history of anemia. It is hypothesized that the hemolysis was precipitated by oxidative stress of an acute infection in the setting of an unstable hemoglobin. The patient was found to have stable hemoglobin of 12 g/dl and methemoglobin of 4.9% in follow up several years later.

Early screening of thalassemia in pregnant women in northern China by capillary electrophoresis for the determination of hemoglobin electrophoresis.

The objective of this study was to analyze the effectiveness of capillary electrophoresis detection of hemoglobin electrophoresis (HE) for the early screening of thalassemia. In the first choice, 974 pregnant women were selected for capillary electrophoresis to detect HE, which showed that 46 of them were abnormal (4.72%), including 16 cases with HbA2<2.5% and 28 cases with HbA2>3.5% and/or HbF≥2.0%. In one case each of HbH and HbBart's abnormal bands was found. The genotype test results showed the presence of thalassemia in 34 cases, using the genotype test results as the gold standard, after calculation it was seen that capillary electrophoresis for HE diagnosis of the occurrence of thalassemia had a sensitivity and specificity of 54.34% and 70.97% (P<0.05). These results suggest that in the screening of thalassemia in northern China, capillary electrophoresis for HE has good application and can be used as one of the routine screening tools, but further confirmation by genotype testing is still needed.

Long-Read Sequencing Identified a Large Novel δ/β-Globin Gene Deletion in a Chinese Family

Objective. Increasingly rare thalassemia has been identified with the advanced use of long-read sequencing based on long-read technology. Here, we aim to present a novel δ/β-globin gene deletion identified by long-read sequencing technology. Methods. Enrolled in this study was a family from the Quanzhou region of Southeast China. Routine blood analysis and hemoglobin (Hb) capillary electrophoresis were used for hematological screening. Genetic testing for common α- and β-thalassemia was carried out using the reverse dot blot hybridization technique. Long-read sequencing was performed to detect rare globin gene variants. Specific gap-polymerase chain reaction (gap-PCR) and/or Sanger sequencing were further used to verify the detected variants. Results. None of the common α- and β-thalassemia mutations or deletions were observed in the family. However, decreased levels of MCV, MCH, and abnormal Hb bands were observed in the family members, who were suspected as rare thalassemia carriers. Further, long-read sequencing demonstrated a large novel 7.414 kb deletion NG_000007.3:g.63511_70924del partially cover HBB and HBD globin genes causing delta-beta fusion gene in the proband. Parental verification indicated that the deletion was inherited from the proband’s father, while none of the globin gene variants were observed in the proband’s mother. In addition, the novel δ/β-globin gene deletion was further verified by gap-PCR and Sanger sequencing. Conclusion. In this study, we first present a large novel δ/β-globin gene deletion in a Chinese family using long-read sequencing, which may cause δβ-thalassemia. This study further enhances that long-read sequencing would be applied as a sharp tool for detecting rare and novel globin gene variants.

Idiopathic multicentric castleman’s disease mimicking immunoglobulin G4-related disease responding well to Bortezomib: a case report

BackgroundCastleman’s disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated immunological dysfunction. ImmunoglobulinG4-related disease (IgG4-RD) is a collection of systemic disorders that affect numerous organs and are also referred to as IgG4-associated sclerosing diseases. CD and IgG4-RD are difficult to separate because they may manifest similar commin clinical features.Case presentationThis case describes a 53-year-old female who, during routine medical check-up, exhibited a progressive increase in serum globulin levels and a simultaneous worsening of anemia symptoms, raising concern for a clonal plasma cell disease such as myeloma. However, bone marrow punctures did not reveal any abnormal plasma cells. Also, serum and urine immunofixation electrophoresis demonstrated no abnormal monoclonal protein bands. In addition, several laboratory findings excluded chronic liver disease, chronic infections caused by bacteria or viruses. Later, we found elevated serum IgG4 levels (10,700 mg/L), and identified multiple enlarged lymph nodes throughout the patient’s body. Axillary lymph node aspiration revealed no abnormal lymphocytes, ruling out the possibility of lymphoma. Pathological morphology of the axillary lymph revealed a large number of plasma cells in the lymphatic follicles. In addition, there was a reduction in lymphatic follicle size and apoptosis of the germinal centres. Immunohistochemistry revealed IgG4+/IgG + in > 40% of cells, and more than 100 IgG4 + cells per high powered field (HPF) of specimen. As of now, finding strongly suggested IgG4-RD. This patient was treated with glucocorticoids and various immunosuppressive drugs, such as prednisone, cyclosporine, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine and hydroxychloroquine. Unfortunately, the patient did not recover. Ultimately, idiopathic multicentric Castleman disease (iMCD) was diagnosed in relation to the patient’s clinical presentation and laboratory tests, and after combination chemotherapy (VCD: Bortezomib, Cyclophosphamide and Dexamethasone), durable remission was achieved without serious adverse effects. During the follow-up period of one year and ten months, the patient remained stable.ConclusionThe diagnosis of Castleman must be distinguished from other disorders such as IgG4-RD, malignant lymphoma, reactive hyperplasia of various lymph nodes (mostly caused by viral infections), plasmacytoma, advanced HIV and rheumatic diseases. Besides observing systemic symptoms, laboratory tests such as immunoglobulin levels, complement levels, interleukin levels, and C-reactive protein levels should also be performed in order to determine a diagnosis.