scholarly journals Endocrine and Bone Complications inβ-Thalassemia Intermedia: Current Understanding and Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Adlette Inati ◽  
MohammadHassan A. Noureldine ◽  
Anthony Mansour ◽  
Hussein A. Abbas
Keyword(s):  
Optimal Treatment ◽  
Current Understanding ◽  
Clinical Settings ◽  
Thalassemia Intermedia ◽  
The Past ◽  
Clinical Forms ◽  
Molecular Features ◽  
Hb E ◽  
Hb H Disease ◽  
Bone Complications

Thalassemia intermedia (TI), also known as nontransfusion dependent thalassemia (NTDT), is a type of thalassemia where affected patients do not require lifelong regular transfusions for survival but may require occasional or even frequent transfusions in certain clinical settings and for defined periods of time. NTDT encompasses three distinct clinical forms:β-thalassemia intermedia (β-TI), Hb E/β-thalassemia, andα-thalassemia intermedia (Hb H disease). Over the past decade, our understanding of the molecular features, pathophysiology, and complications of NTDT particularlyβ-TI has increased tremendously but data on optimal treatment of disease and its various complications are still lacking. In this paper, we shall review a group of commonly encountered complications inβ-TI, mainly endocrine and bone complications.

The Role of Histones and Heparin in Sepsis: A Review

2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li
Keyword(s):  
Septic Shock ◽  
Multiple Organ ◽  
Clinical Settings ◽  
The Past ◽  
Life Saving ◽  
Extracellular Histones ◽  
Sepsis And Septic Shock ◽  
Development And Management ◽  
Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

scholarly journals The New Keynesian Synthesis

1993 ◽  
Vol 7 (1) ◽  
pp. 5-22 ◽  
Author(s):  
David Romer
Keyword(s):  
Current Understanding ◽  
New Keynesian ◽  
Price Rigidity ◽  
Rapid Progress ◽  
The Past ◽  
Nominal Rigidity

The new Keynesians made more rapid progress in understanding the microeconomics of unemployment than in understanding the microeconomics of nominal price rigidity. But the past five years have seen important breakthroughs in this second area. This paper will describe these breakthroughs, discuss our current understanding of nominal rigidity, and assess the work that remains to be done.

scholarly journals Inventing the Past, Re-Writing the Present

2020 ◽  
Vol 31 (2) ◽  
pp. 61-72
Author(s):  
Jurgita Staniškytė
Keyword(s):  
Current Understanding ◽  
Historical Events ◽  
The Past ◽  
Hybrid Approaches ◽  
Reality Effect ◽  
The Subject ◽  
The Baltic ◽  
Historical Past

In recent years an increasing number of performances on the Baltic theatre stage attempt to escape the dominant understanding of “performing history” as a repetition or reinforcement of the monumental representations of the historical past or as a (re)production of “mythistory” (Joseph Mali). Lithuanian creators of performances about history increasingly choose hybrid approaches of representation, merging memorialization and critique, imagination and fact, documents and speculative inventions as forms of engagement with the past. This playful re-imagination of the historical past serves as a creative laboratory, where audience ability to recognize and/or resist historical manipulations as well as to embrace plural and polyphonic nature of memory are tested. In some cases, however, Lithuanian theatre creators are interested in “truthful” or “authentic” representations of personal memories, rather than a performative investigation ofmechanisms of production of the “reality effect” in historiography and their impact on audience perception. This article examines the ways in which historical events are represented on the contemporary Lithuanian theatre stage and, at the same time, addresses the larger issues around the implications of particular theatricalstagings of the past on the current understanding of the subject of history.

scholarly journals Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6039
Author(s):  
Bo Xu ◽  
Hao Wang ◽  
Li Tan
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Embryonic Development ◽  
Cellular Differentiation ◽  
Epigenetic Modification ◽  
Current Understanding ◽  
Future Perspectives ◽  
Cancer Hallmarks ◽  
The Past

DNA methylation (5-methylcytosine, 5mC) was once viewed as a stable epigenetic modification until Rao and colleagues identified Ten-eleven translocation 1 (TET1) as the first 5mC dioxygenase in 2009. TET family genes (including TET1, TET2, and TET3) encode proteins that can catalyze 5mC oxidation and consequently modulate DNA methylation, not only regulating embryonic development and cellular differentiation, but also playing critical roles in various physiological and pathophysiological processes. Soon after the discovery of TET family 5mC dioxygenases, aberrant 5mC oxidation and dysregulation of TET family genes have been reported in breast cancer as well as other malignancies. The impacts of aberrant 5mC oxidation and dysregulated TET family genes on the different aspects (so-called cancer hallmarks) of breast cancer have also been extensively investigated in the past decade. In this review, we summarize current understanding of the causes and consequences of aberrant 5mC oxidation in the pathogenesis of breast cancer. The challenges and future perspectives of this field are also discussed.

scholarly journals Options and Limitations in Clinical Investigation of Bacterial Biofilms

2018 ◽  
Vol 31 (3) ◽  
Author(s):  
Maria Magana ◽  
Christina Sereti ◽  
Anastasios Ioannidis ◽  
Courtney A. Mitchell ◽  
Anthony R. Ball ◽  
...  
Keyword(s):  
Clinical Investigation ◽  
Bacterial Biofilm ◽  
Clinical Settings ◽  
Microbial Composition ◽  
The Past ◽  
Methodological Research ◽  
Current Trends ◽  
Literature Searches ◽  
Biofilm Development ◽  
Multispecies Biofilms

SUMMARYBacteria can form single- and multispecies biofilms exhibiting diverse features based upon the microbial composition of their community and microenvironment. The study of bacterial biofilm development has received great interest in the past 20 years and is motivated by the elegant complexity characteristic of these multicellular communities and their role in infectious diseases. Biofilms can thrive on virtually any surface and can be beneficial or detrimental based upon the community's interplay and the surface. Advances in the understanding of structural and functional variations and the roles that biofilms play in disease and host-pathogen interactions have been addressed through comprehensive literature searches. In this review article, a synopsis of the methodological landscape of biofilm analysis is provided, including an evaluation of the current trends in methodological research. We deem this worthwhile because a keyword-oriented bibliographical search reveals that less than 5% of the biofilm literature is devoted to methodology. In this report, we (i) summarize current methodologies for biofilm characterization, monitoring, and quantification; (ii) discuss advances in the discovery of effective imaging and sensing tools and modalities; (iii) provide an overview of tailored animal models that assess features of biofilm infections; and (iv) make recommendations defining the most appropriate methodological tools for clinical settings.

scholarly journals The Role of Phosphatases in Nuclear Envelope Disassembly and Reassembly and Their Relevance to Pathologies

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 687 ◽  
Author(s):  
Florentin Huguet ◽  
Shane Flynn ◽  
Paola Vagnarelli
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Nuclear Envelope ◽  
Current Understanding ◽  
The Past ◽  
Pathological Conditions ◽  
Regulation Of Cell Cycle

The role of kinases in the regulation of cell cycle transitions is very well established, however, over the past decade, studies have identified the ever-growing importance of phosphatases in these processes. It is well-known that an intact or otherwise non-deformed nuclear envelope (NE) is essential for maintaining healthy cells and any deviation from this can result in pathological conditions. This review aims at assessing the current understanding of how phosphatases contribute to the remodelling of the nuclear envelope during its disassembling and reformation after cell division and how errors in this process may lead to the development of diseases.

Listening to the Musicking Body

2018 ◽  
pp. 417-436
Author(s):  
Youn Kim
Keyword(s):  
Human Body ◽  
Auditory Perception ◽  
The Body ◽  
Current Understanding ◽  
Historical Changes ◽  
The Past ◽  
Late Nineteenth ◽  
Shed Light

Listening is generally discussed in connection with auditory perception, with the ear as the primary perceptual organ. Recently, however, more comprehensive approaches are being emphasized along with the need to understand listening in the context of cultural and historical changes. This chapter investigates the plasticity of the idea of listening, both across disciplines and across historical contexts. By engaging with various discourses on seeing, hearing, and kinesthetics in the late nineteenth and early twentieth centuries, the present chapter examines how a holistic conceptualization of listening that goes beyond the ear and functions in the context of the whole human body emerged and argues how understanding the past can shed light on the current understanding of music and the body.

scholarly journals Globin Chain Synthesis in the Marrow and Reticulocytes of Beta Thalassemia, Hemoglobin H Disease, and Beta Delta Thalassemia

Blood ◽  
1972 ◽  
Vol 40 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Mordechai Shchory ◽  
Bracha Ramot
Keyword(s):  
Bone Marrow ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Thalassemia Intermedia ◽  
Thalassemia Minor ◽  
Order Of Magnitude ◽  
Hb H Disease ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract α, β, and γ globin chain synthesis in bone marrow and peripheral blood reticulocytes were studied in two patients with thalassemia major, two with thalassemia intermedia, one with thalassemia minor, one with Hb H disease, and one with homozygous βδ-thalassemia. Nine nonthalassemic patients served as controls. In thalassemia major, a marked imbalance of α- to β-chain synthesis was found in the bone marrow as well as in reticulocytes. The imbalance, however, was slightly more evident in the latter. In the patients with thalassemia intermedia and minor the α- to β-globin chain ratios in the reticulocytes were of the same order of magnitude, despite the marked clinical differences between thalassemia intermedia and minor. A balanced synthesis was found in the bone marrow of the patient with thalassemia minor. The bone marrow globin synthesis in thalassemia intermedia was not studied. Contrary to that in Hb H disease and βδ-thalassemia, the imbalance was more apparent in the bone marrow. In the latter, no evidence for imbalance was detected in the reticulocytes. These results point out the need for further studies on globin chain synthesis in the bone marrow and reticulocytes of patients With the various thalassemia syndromes and the effect of the free globin chain pool on those results.

New Directions in the Treatment of Glioblastoma

2018 ◽  
Vol 38 (01) ◽  
pp. 050-061 ◽  
Author(s):  
Zachary Reitman ◽  
Frank Winkler ◽  
Andrew Elia
Keyword(s):  
Standard Of Care ◽  
Multimodality Treatment ◽  
Genetic Alterations ◽  
Current Standard ◽  
The Past ◽  
Molecular Features ◽  
Genome Wide ◽  
New Directions ◽  
The Central Nervous System ◽  
Better Than

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.

scholarly journals Parental self-medication with antibiotics for children promotes antibiotic over-prescribing in clinical settings in China

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Jiayao Xu ◽  
Xiaomin Wang ◽  
Kai Sing Sun ◽  
Leesa Lin ◽  
Xudong Zhou
Keyword(s):  
Antibiotic Use ◽  
Antibiotic Prescribing ◽  
Clinical Settings ◽  
Cross Sectional Survey ◽  
Self Medication ◽  
Cross Sectional ◽  
Prescribing Behavior ◽  
The Past ◽  
Outpatient Settings ◽  
The Impact

Abstract Background Self-medication with antibiotics (SMA) is one of the most dangerous inappropriate antibiotic use behaviors. This study aims to investigate the impact of parental SMA for children before a consultation on their doctor’s subsequent antibiotic prescribing behavior, including intravenous (IV) antibiotic use in the clinical setting of China. Methods A cross-sectional survey was conducted between June 2017 and April 2018 in three provinces of China. A total of 9526 parents with children aged 0–13 years were investigated. Data from 1275 parents who had self-medicated their children and then visited a doctor in the past month were extracted and analyzed. Results One-third (410) of the studied children had parental SMA before the consultation and 83.9% of them were subsequently prescribed antibiotics by doctors. Children with parental SMA were more likely to be prescribed antibiotics (aOR = 7.79, 95% CI [5.74–10.58]), including IV antibiotics (aOR = 3.05, 95% CI [2.27–4.11]), and both oral and IV antibiotics (aOR = 3.42, 95% CI [2.42–4.84]), than children without parental SMA. Parents with SMA behaviors were more likely to request antibiotics (aOR = 4.05, 95% CI [2.59–6.31]) including IV antibiotics (aOR = 2.58, 95% CI [1.40–4.76]), and be fulfilled by doctors (aOR = 3.22, 95% CI [1.20–8.63]). Conclusions Tailored health education for parents is required in both community and clinical settings to discourage parental SMA for children. The doctors should not prescribe unnecessary antibiotics to reinforce parents’ SMA behaviors. We recommend expanding the current IV antibiotics ban in outpatient settings of China to cover outpatient pediatrics.

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