Annals of medicine
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Review
DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation.
DNA methylation is considered an essential epigenetic event during leukaemogenesis and the emergence of drug resistance, which is primarily regulated by DNA methyltransferases. DNA methyltransferase-1 (DNMT1) is one of the members of DNA methyltransferases, in charge of maintaining established methylation. Recently, DNMT1 is shown to promote malignant events of cancers through the epigenetic and non-epigenetic processes. ⋯ In this review, we summarized the recent understanding of DNMT1 in normal haematopoiesis and AML and discussed the possible functions of DNMT1 in promoting the development of AML and predicting the sensitivity of hypomethylation agents to better understand the relationship between DNMT1 and AML and to look for new hope to treat AML patients. Key messagesThe function of DNA methyltransferase-1 in acute myeloid leukaemia. DNA methyltransferase-1 predicts the sensitivity of drug and involves the emergence of drug resistance.
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Nail conditions are not only aesthetic concerns, and nail changes may be a clue to an underlying systemic diseases or infection. Without timely treatment, nail diseases can continue to worsen and significantly impair performance of daily activities and reduce quality of life. Examination of the nails is essential at every medical visit, and may uncover important findings. ⋯ Key messagesNail disease is not only a cosmetic issue, as nail changes can indicate the presence of a serious underlying systemic disease, infection or malignancy. Nail pain and changes associated with NP are physically and emotionally distressing and may contribute to functional impairment and diminished quality of life. LM is a hallmark sign of subungual melanoma and this finding warrants further investigation to rule out malignancy.
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Sickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low. ⋯ Young adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted.KEY MESSAGESYoung adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents.Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization.No significant association of HU adherence to patients' sex, socio-economic status and distance from hospital.
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To summarise the process of conversion of epidural labour analgesia to anaesthesia for caesarean delivery and explore the relationship between duration of labour analgesia and conversion. ⋯ Prolonged duration of epidural labour analgesia increases the possibility of having an invalid epidural catheter, resulting in an increased risk of conversion failure from epidural labour analgesia to epidural surgical anaesthesia. Further, this risk is higher when the time exceeds 8 h. KEY MESSAGESProlonged duration of epidural labour analgesia > 8 h is associated with conversion failure.If it is impossible to judge whether the conversion is successful immediately, spinal anaesthesia should be administered to minimise complications.
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Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.g. irritable bowel syndrome, temporomandibular disorder, and fibromyalgia syndrome) that affect remote body regions. Here, we describe the rationale and design of an NIH-funded multicenter clinical trial comparing the effectiveness of topical and/or systemic medication for alleviating pain and normalizing pain- relevant biomarkers among women with VBD-p and VBD-c. ⋯ Vestibulodynia UPDATe is a multi-centre, two-by-two factorial designed randomized, double-blind, placebo-controlled trial registered at clinical trials.gov (NCT03844412). This work is supported by the R01 HD096331 awarded to Drs. Nackley, Rapkin, Geller and Carey by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).Key messagesPeripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs.This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles.We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches.