Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining

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Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.     

Sex-Specific Associations of Iron-Anemia Status With Hemoglobin A1C Levels Among Hispanics/Latinos Without Self-Reported Diabetes Mellitus: The Hispanic Community Health Study/Study of Latinos

ObjectiveThe objective of this study was to examine the sex-specific associations of mutually exclusive iron-anemia status categories with hemoglobin A1C (HbA1C) levels among U.S. Hispanics/Latinos without self-reported diabetes mellitus.MethodsBaseline cross-sectional data (7247 women and 4904 men without self-reported diabetes mellitus) from the Hispanic Community Health Study/Study of Latinos were analyzed. Per the American Diabetes Association’s defined criteria, based on HbA1C levels, the participants were categorized as having normoglycemia, prediabetes, or probable diabetes mellitus. The iron-anemia status categories were as follows: no anemia and no iron deficiency (reference), iron deficiency, iron deficiency anemia (IDA), and non-iron deficiency anemia (non-IDA). Survey multinomial logistic regression models were used to examine the sex-specific associations of iron-anemia status with HbA1C levels after adjusting for sociodemographic, lifestyle, and clinical factors.ResultsThe age-standardized prevalence of iron-anemia status categories differed by sex. Compared with those with no anemia and no iron deficiency and normoglycemia, women with IDA had higher odds of having prediabetes (odds ratio [OR], 2.18; 95% CI, 1.64-2.89) and probable diabetes mellitus (OR, 3.59; 95% CI, 1.62-7.99) based on HbA1C levels; men with non-IDA had higher odds of having probable diabetes mellitus (OR, 2.97; 95% CI, 1.13-7.78) based on HbA1C levels. All other associations did not reach statistical significance.ConclusionAmong U.S. Hispanics/Latinos without self-reported diabetes mellitus, the age-standardized prevalence of iron deficiency, IDA, and non-IDA is high and varies by sex. Women with IDA had higher odds of having prediabetes and probable diabetes mellitus, defined based on HbA1C levels. Men with non-IDA had higher odds of having probable diabetes mellitus, defined based on HbA1C levels. Iron-anemia status should be considered while interpreting elevated HbA1C levels among U.S. Hispanics/Latinos without self-reported diabetes mellitus.     

Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia

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Membrane effects of imidoesters in hereditary stomatocytosis

The marked increase in cation (Na⁺, K⁺) permeability that results in swollen, cup-shaped red cells in the hereditary stomatocytosis syndrome can be corrected in vitro with a bifunctional crosslinking reagent, dimethyl adipimidate (DMA). ⁴⁵Ca influx in intact RBC, ⁴⁵Ca efflux in red ghosts, and ⁴⁵Ca retention in red ghosts are normal and not influenced by DMA. Endocytosis in resealed red ghosts is strikingly impaired but becomes normal if cells are first treated with 2 mM DMA. Protein kinase mediated phosphorylation of membrane proteins by AT³²P–only 20–40% of normal control values in both short-term (5 min) and more extended (60 min) incubations–is not improved by DMA. After reaction of ¹⁴C-DMA with stomatocytes, radiolabel is found associated with phosphatidyl serine and phosphatidyl ethanolamine and is also widely distributed among membrane proteins. Cation permeability of stomatocytes is corrected at DMA concentrations (1 mM) that result in barely detectable crosslinking of aminophospholipids or proteins, suggesting that either crosslinking of a minor component present in only small quantities or intramolecular (rather than intermolecular) crosslinking is responsible for the permeability effects. DMA, whose maximal crosslinking dimension is 7.3–9 Å, is the most effective bifunctional imidoester of those tested. Shorter (dimethyl malonimidate) or longer (dimethylsuberimidate) reagents are either less effective than DMA or totally without effect.     

Dermatoglyphic asymmetry in healthy and pathological subjects

The amount of asymmetry in various digital and palmar characters found in healthy and pathological individuals (presenting Cooley's anemia, cleft lip, cleft palate and breast cancer) was examined. Males with cleft palate presented higher asymmetry index values than did healthy males. No great differences were found in the other pathologies, while different behaviour in the two sexes was noted. Work supported by M.U.R.S.T. 60%     

Role of TMPRSS6 rs855791 (T > C) polymorphism in reproductive age women with iron deficiency anemia from Lahore,Pakistan

BackgroundIron deficiency anemia (IDA) is the highest nutritional deficiency worldwide. It is a multifactorial disease, with a higher morbidity rate. TMPRSS6 polymorphisms importantly rs855791 is found to play an essential role in iron homeostasis in the human body. The rs855791 (T > C) polymorphism is highly associated with iron levels, and multiple blood parameters, leading to IDA. The role of TMPRSS6 rs855791 polymorphism and the significance of complete blood count (CBC) parameters in the pathogenesis of IDA is not yet studied in the Pakistani population.MethodsWe enrolled 113 cases and 136 controls to conduct a case control study. Complete blood count (CBC) and iron parameters were analyzed for association studies. PCR-RFLP based genotyping was performed.ResultsThe TMPRSS6 rs855791 (T > C) polymorphism is significantly associated with IDA pathogenesis as observed in the codominant model and recessive models (P < 0.05, OR: 1.5 and 95% CI: 0.9, 2.6, P < 0.05, OR: 0.5 and 95% CI: 0.2, 0.9 respectively). Elderly women among cases (30–49 years) were found to be more susceptible to IDA (P < 0.05, AOR: 2.1 and 95% CI: 1.0, 4.2). The most significant parameters associated with IDA were red blood cell count (RBC) and hematocrit (Hct%) (P < 0.05, AOR: 16.5, 95% CI: 7.6, 35.9 and P < 0.05, AOR: 10.1, 95% CI: 2.5, 41.6, respectively).ConclusionTMPRSS6 polymorphism at rs855791 (T > C) is significantly associated with IDA susceptibility in reproductive age women in Pakistan. Age, RBC count and Hct% are found to play an important role in IDA pathogenesis in our study population.     

MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia

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Iron in blood cells: Function,relation to disease,and potential for magnetic separation

Iron in blood cells has several physiological functions like transporting oxygen to cells and maintaining iron homeostasis. Iron is primarily contained in red blood cells (RBCs), but monocytes also store iron as these cells are responsible for the recycling of senescent RBCs. Iron also serves an important role related to the function of different leukocytes. In inflammation, iron homeostasis is dependent on cytokines derived from T cells and macrophages. Fluctuations of iron content in the body lead to different diseases. Iron deficiency, which is also known as anemia, hampers different physiological processes in the human body. On the other hand, genetic or acquired hemochromatosis ultimately results in iron overload and leads to the failure of different vital organs. Different diagnoses and treatments are developed for these kinds of disorders, but the majority are costly and suffer from side effects. To address this issue, magnetophoresis could be an attractive technology for the diagnosis (and in some cases treatment) of these pathologies due to the paramagnetic character of the cells containing iron. In this review, we discuss the main functions of iron in blood cells and iron-related diseases in humans and highlight the potential of magnetophoresis for diagnosing and treating some of these disorders.