MRD in Acute Leukemias: Lessons Learned from Acute Promyelocytic Leukemia.

Advances in molecular biology, polymerase chain reaction (PCR), and next-generation sequencing (NGS) have transformed the concept of minimal residual disease (MRD) from a philosophical idea into a measurable reality. Acute promyelocytic leukemia (APL) leads the way in this transformation, initially using PCR to detect MRD in patients in remission, and more recently, aiming to eliminate it entirely with modern treatment strategies. Along the way, we have gained valuable insights that, when applied to other forms of acute leukemia, hold the potential to significantly improve the outcomes of these challenging diseases.

β2-glycoprotein I promotes the clearance of circulating mitochondria.

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood.

Erythrophagocytosis in autoimmune immunoglobulin A-mediated hemolysis.

Introduction: Warm antibody-mediated autoimmune hemolysis (WAIHA) is most often due to immunoglobulin G (IgG) antibodies and is detected by direct antiglobulin test (DAT). However, about 10% cases of hemolytic anemia are DAT negative. Herein, we describe a patient with DAT-negative hemolytic anemia due to an anti-IgA antibody.

Downregulated KLF2 in polycythemia vera and essential thrombocythemia induces prothrombotic gene expression.

Thromboses are major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) diseases associated with JAK2V617F mutation. However, the molecular mechanism(s) of increased thrombosis in PV and ET remain unknown. Kruppel-like factor 2 (KLF2) is a transcription factor that regulates expression of genes associated with inflammation and thrombosis; the absence of KLF2 in neutrophils causes thrombosis by inducing tissue factor.

Quality standards for the management of non-alcoholic fatty liver disease (NAFLD): consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group.

Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care.

Phytomedicinal therapeutics for male infertility: critical insights and scientific updates.

Infertility is a significant cause of anxiety, depression, and social stigma among couples and families. In such cases, male reproductive factors contribute widely to the extent of 20-70%. Male infertility is a multifactorial disease with several complications contributing to its diagnosis.

Accommodative and pupillary dysfunctions in concussion/mild traumatic brain injury: A Review.

Background: Visual dysfunctions are common in individuals following concussion/mild traumatic brain injury (C/mTBI). Many deficits have been uncovered in their oculomotor system, such as in the pupil and accommodation.

Objective: To describe the static and dynamic abnormalities in the pupillary and accommodative systems in those with C/mTBI.

Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease.

Objectively-based vergence and accommodative dynamics in mild traumatic brain injury (mTBI): A mini review.

Vergence and accommodation have been critical areas of investigation in those with mild traumatic brain injury (mTBI). In this mini-review, the major laboratory studies in the area using objective assessment of vergence and accommodative dynamics in this population are discussed. These include the basic findings, their diagnostic and therapeutic implications, potential study limitations, and suggested future research directions.

Explanation and Use of Uncertainty Quantified by Bayesian Neural Network Classifiers for Breast Histopathology Images.

Despite the promise of Convolutional neural network (CNN) based classification models for histopathological images, it is infeasible to quantify its uncertainties. Moreover, CNNs may suffer from overfitting when the data is biased. We show that Bayesian-CNN can overcome these limitations by regularizing automatically and by quantifying the uncertainty.

Efficacy of ultrasound-guided erector spinae plane block following breast surgery - A double-blinded randomised, controlled study.

Background And Aims: Regional anaesthesia has been used to reduce acute post-operative pain as well as opioid-related side effects in breast cancer surgery. Erector spinae plane (ESP) block is a relatively new fascial plane block being tried in various surgical procedures. Our study is a double-blind randomised trial, designed to prove the efficacy of this block in breast surgeries.

How Do Red Blood Cells Die?

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive.

Metabolic Imaging in Non-Alcoholic Fatty Liver Disease: Applications of Magnetic Resonance Spectroscopy.

Non-alcoholic fatty liver disease (NAFLD) is poised to dominate the landscape of clinical hepatology in the 21st century. Its complex, interdependent aetiologies, non-linear disease progression and uncertain natural history have presented great challenges to the development of effective therapies. Progress will require an integrated approach to uncover molecular mediators, key pathogenic milestones and response to intervention at the metabolic level.

Role of TGF-β signalling in PCOS associated focal segmental glomerulosclerosis.

Research on polycystic ovarian syndrome (PCOS) remains intense due to its evolving impact on metabolism, reproduction and cardiovascular function. Changes in metabolic pathways can also significantly impact renal function including the development of Focal Segmental Glomerulosclerosis (FSGS), one of the most highly investigated renal diseases. In FSGS, scarring of the glomerulus vascular tuft damages the kidneys.

Anti-inflammatory and wound healing potential of a clove oil emulsion.

Emulsion formulations of essential oils are of major interest due to their relative biosafety, biocompatibility and good pharmacological potential. Their structural constituents (oil and water phase) facilitate ready solubilization of incorporated hydrophilic/lipophilic actives for their targeted delivery. In the present study, m5S cells were tested for their viability at various concentrations of clove oil and an alkyl polyglucoside emulsifier, viz.

Thrombotic, inflammatory, and HIF-regulated genes and thrombosis risk in polycythemia vera and essential thrombocythemia.

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)-regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes.

Cofilin-1-induced actin reorganization in stored platelets.

Background: During platelet storage, there are extensive changes in cytoskeleton and phosphatidylserine exposure. The intrinsic mitochondrial pathway of apoptosis, activated in stored platelets, is a major mediator these changes. Cofilin-1 is an effector of actin reorganization.

Detecting chronic liver disease: are liver function tests the solution?

By 2020, chronic liver disease will have eclipsed ischaemic heart disease as the leading cause of working life years lost in the UK. As mortality from chronic liver disease continues to rise, the landscape of aetiology has shifted from infectious to non-communicable causes. In parallel with the growing prevalence of obesity and type 2 diabetes, non-alcoholic fatty liver disease is estimated to affect 25% of the UK adult population.

Lisinopril-Induced Angioedema in a Patient with Plasma Prekallikrein Deficiency.

Angiotensin-converting enzyme (ACE) inhibitors are extensively prescribed to treat patients with hypertension, congestive heart failure, and diabetic nephropathy. A small fraction of these patients (approximately 0.7%) develop angioedema, manifested by swelling of the lips and oropharynx.

Mapping transactional analysis to clinical leadership models.

Leaders in today's NHS face the unenviable task of reconciling rising demand, frozen resource allocation and increasing accountability. As the NHS itself stands at the nexus of an unstable political and socioeconomic landscape, its future success relies largely on its ability to nurture excellence, to encourage open communication within and across health-care teams, and to inspire its workforce through exemplary leadership and followership. Key to these endeavours are clinicians on the 'shop floor', whose daily interactions with patients and staff help to shape prevailing culture and drive progress through quality improvement and leadership initiatives.

Drug Development for Nonalcoholic Fatty Liver Disease: Landscape and Challenges.

Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in industrialized economies. With no licensed treatment currently available, together with a growing prevalence that parallels global increases in obesity and type 2 diabetes, NAFLD will dominate the landscape of hepatology for the foreseeable future. A multifaceted etiopathogenesis, paucity of reproducible preclinical models that effectively recreate human NAFLD, and lack of robust surrogate trial endpoints have presented major hurdles in drug discovery and development.