scholarly journals Biosynthesis and Functions of Mycothiol, the Unique Protective Thiol of Actinobacteria

2008 ◽  
Vol 72 (3) ◽  
pp. 471-494 ◽  
Author(s):  
Gerald L. Newton ◽  
Nancy Buchmeier ◽  
Robert C. Fahey
Keyword(s):  
Transcriptional Regulation ◽  
Future Study ◽  
Streptomyces Coelicolor ◽  
Alkylating Agents ◽  
Current Evidence ◽  
Mercapturic Acids ◽  
Nitrogen Species ◽  
Future Studies ◽  
Disulfide Reductase ◽  
Reducing Environment

SUMMARY Mycothiol (MSH; AcCys-GlcN-Ins) is the major thiol found in Actinobacteria and has many of the functions of glutathione, which is the dominant thiol in other bacteria and eukaryotes but is absent in Actinobacteria. MSH functions as a protected reserve of cysteine and in the detoxification of alkylating agents, reactive oxygen and nitrogen species, and antibiotics. MSH also acts as a thiol buffer which is important in maintaining the highly reducing environment within the cell and protecting against disulfide stress. The pathway of MSH biosynthesis involves production of GlcNAc-Ins-P by MSH glycosyltransferase (MshA), dephosphorylation by the MSH phosphatase MshA2 (not yet identified), deacetylation by MshB to produce GlcN-Ins, linkage to Cys by the MSH ligase MshC, and acetylation by MSH synthase (MshD), yielding MSH. Studies of MSH mutants have shown that the MSH glycosyltransferase MshA and the MSH ligase MshC are required for MSH production, whereas mutants in the MSH deacetylase MshB and the acetyltransferase (MSH synthase) MshD produce some MSH and/or a closely related thiol. Current evidence indicates that MSH biosynthesis is controlled by transcriptional regulation mediated by σB and σR in Streptomyces coelicolor. Identified enzymes of MSH metabolism include mycothione reductase (disulfide reductase; Mtr), the S-nitrosomycothiol reductase MscR, the MSH S-conjugate amidase Mca, and an MSH-dependent maleylpyruvate isomerase. Mca cleaves MSH S-conjugates to generate mercapturic acids (AcCySR), excreted from the cell, and GlcN-Ins, used for resynthesis of MSH. The phenotypes of MSH-deficient mutants indicate the occurrence of one or more MSH-dependent S-transferases, peroxidases, and mycoredoxins, which are important targets for future studies. Current evidence suggests that several MSH biosynthetic and metabolic enzymes are potential targets for drugs against tuberculosis. The functions of MSH in antibiotic-producing streptomycetes and in bioremediation are areas for future study.

scholarly journals Education Research: Flipped classroom in neurology

Neurology ◽  
2019 ◽  
Vol 93 (1) ◽  
pp. e106-e111 ◽  
Author(s):  
Stefano Sandrone ◽  
Jimmy V. Berthaud ◽  
Chad Carlson ◽  
Jacquelyne Cios ◽  
Neel Dixit ◽  
...  
Keyword(s):  
Flipped Classroom ◽  
Medical Knowledge ◽  
Current Evidence ◽  
Health Care Education ◽  
Future Studies ◽  
Small Collection ◽  
Curricular Implementation ◽  
Patient Complexity ◽  
Unequal Access ◽  
Faculty Time

How to most effectively deliver a large amount of information in an engaging environment that encourages critical thinking is a question that has long plagued educators. With ever-increasing demands on both resident and faculty time, from shrinking duty hours to increased patient complexity, combined with the exponential growth of medical knowledge and unequal access to the spectrum of neurologic subspecialties around the country, this question has become especially pertinent to neurology residency training. A team of educators from the American Academy of Neurology's A.B. Baker Section on Neurological Education sought to review the current evidence regarding the implementation of the flipped classroom format. This educational model has only recently been applied to health care education along the training continuum, and a small collection of articles has, so far, used disparate methods of curricular implementation and assessment. While the feedback from learners is generally positive, a number of obstacles to implementation exist, most notably learner time commitments. These are presented with discussion of potential solutions along with suggestions for future studies.

Home telehealth for chronic disease management: A systematic review and an analysis of economic evaluations

2009 ◽  
Vol 25 (03) ◽  
pp. 339-349 ◽  
Author(s):  
Julie Polisena ◽  
Doug Coyle ◽  
Kathryn Coyle ◽  
Sarah McGill
Keyword(s):  
Chronic Diseases ◽  
Current Evidence ◽  
Economic Evaluations ◽  
Future Studies ◽  
Provider Perspectives ◽  
Healthcare Decision Making ◽  
Home Telehealth ◽  
Using Data ◽  
The Cost

Objectives:The research objectives were two-fold: first, to systematically review the literature on the cost-effectiveness of home telehealth for chronic diseases, and second to develop a framework for the conduct of economic evaluation of home telehealth projects for patients with chronic diseases.Methods:A comprehensive literature search identified twenty-two studies (n= 4,871 patients) on home telehealth for chronic diseases published between 1998 and 2008. Studies were reviewed in terms of their methodological quality and their conclusions.Results:Home telehealth was found to be cost saving from the healthcare system and insurance provider perspectives in all but two studies, but the quality of the studies was generally low. An evaluative framework was developed which provides a basis to improve the quality of future studies to facilitate improved healthcare decision making, and an application of the framework is illustrated using data from an existing program evaluation of a home telehealth program.Conclusions:Current evidence suggests that home telehealth has the potential to reduce costs, but its impact from a societal perspective remains uncertain until higher quality studies become available.

Transcriptional Regulation of the SCL Locus: Identification of an Enhancer That Targets Primitive Erythroid Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1599-1599
Author(s):  
Eric Delabesse* ◽  
Sarah Ogilvy* ◽  
Michael A. Chapman ◽  
Berthold Göttgens ◽  
Anthony R. Green
Keyword(s):  
Transcriptional Regulation ◽  
T Cell ◽  
Genomic Sequence ◽  
Fetal Liver ◽  
Current Evidence ◽  
Cell Leukaemia ◽  
Bhlh Protein ◽  
Comparative Genomic ◽  
Sequence Comparisons

Abstract The stem cell leukaemia (SCL) gene encodes a bHLH protein that is essential for the formation of all haematopoietic lineages. In addition, maintenance of SCL expression is required for normal differentiation along the erythroid and megakaryocytic lineages, whereas failure to downregulate SCL transcription during T-cell differentiation is associated with T-cell ALL. Current evidence therefore demonstrates that appropriate transcriptional regulation is essential for the biological functions of SCL and this focuses attention on the mechanisms whereby transcription of SCL itself is initiated and maintained. We have previously used biochemical, comparative genomic and transgenic assays to identify 5 distinct enhancers which target different subdomains of the normal SCL expression pattern. However these enhancers do not explain how erythroid expression of SCL is achieved and we have postulated the existence of an additional erythroid enhancer. It is also unclear whether the known SCL enhancers regulate neighbouring genes within the SCL locus. We have therefore quantitated the transcripts from SCL and its neighbouring genes in a large panel of human and murine haematopoietic cell types. Our results reveal a striking and unexpected co-expression of SCL and its downstream neighbour MAP17 (r=0.8; n=31). We demonstrate the existence of appropriately spliced low abundance SCL-MAP17 fusion transcripts suggesting that co-expression reflects transcriptional read-through rather than a shared enhancer. A systematic survey of histone H3 and H4 acetylation throughout the SCL locus was also performed in both cell lines and primary haematopoietic cells. A peak of acetylation downstream of MAP17 (and 40 kb downstream of SCL exon 1a) was found to correlate with expression of SCL but not other neighbouring genes. This region contains peaks of homology in 4-way genomic sequence comparisons (human/dog/mouse/rat) and functions as an erythroid-restricted enhancer in vitro. Morever, in transgenic mice this enhancer directs b-galactosidase expression to the vast majority of circulating primitive erythroblasts but not to fetal liver definitive erythroblasts.

scholarly journals Transcriptional regulation of the four promoters of the agarase gene (dagA) of Streptomyces coelicolor A3 (2)

Microbiology ◽  
1994 ◽  
Vol 140 (10) ◽  
pp. 2555-2565 ◽  
Author(s):  
L. Servin-Gonzalez ◽  
M. R. Jensen ◽  
J. White ◽  
M. Bibb
Keyword(s):  
Transcriptional Regulation ◽  
Streptomyces Coelicolor

scholarly journals Insulin-Like Growth Factor I and the Pathogenesis of Delirium: A Review of Current Evidence

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Dimitrios Adamis ◽  
David Meagher
Keyword(s):  
Inflammatory Responses ◽  
Well Being ◽  
Adverse Outcomes ◽  
Current Evidence ◽  
Related Factors ◽  
Future Studies ◽  
Medically Ill ◽  
Therapeutic Trials ◽  
Hormone Administration ◽  
Igf I

Delirium is a frequent complication in medically ill elderly patients that is associated with serious adverse outcomes including increased mortality. Delirium risk is linked to older age, dementia, and illness that involves activation of inflammatory responses. IGF-I is increasingly postulated as a key link between environmental influences on body metabolism with a range of neuronal activities and has been described as themaster regulatorof the connection between brain and bodily well-being. The relationships between IGF-I and ageing, cognitive impairment and inflammatory illness further support a possible role in delirium pathogenesis. Five studies of IGF-I in delirium were identified by a systematic review. These conflicting findings, with three of the five studies indicating an association between IGF-1 and delirium occurrence, may relate to the considerable methodological differences in these studies. The relevance of IGF-I and related factors to delirium pathogenesis can be clarified by future studies which account for these issues and other confounding factors. Such work can inform therapeutic trials of IGF-I and/or growth hormone administration.

scholarly journals Metabolic and Bariatric Surgery in Adolescents

2021 ◽  
Author(s):  
Christopher G. Chalklin ◽  
Elizabeth G. Ryan Harper ◽  
Andrew J. Beamish
Keyword(s):  
Bariatric Surgery ◽  
Mental Health Problems ◽  
Age Groups ◽  
Current Evidence ◽  
Future Studies ◽  
Limited Success ◽  
Prevalence Of Obesity ◽  
Metabolic And Bariatric Surgery ◽  
Comorbidity Resolution

Abstract Purpose of Review The prevalence of obesity is increasing in all age groups. Following its success in adults, and with limited success using conservative therapies, metabolic and bariatric surgery (MBS) is increasingly being utilized in adolescents. This review highlights the current evidence and guidelines supporting its use. Recent Findings Safety and efficacy mirror results seen in adults. The most recent evidence, as outcomes enter the long term, suggests that comorbidity resolution, including diabetes and hypertension, can even outperform that of adults. Mental health problems persist despite good weight loss. Overall, the positive early weight and comorbidity outcomes are well sustained into the long term. Summary There is a growing need to prevent and treat adolescent obesity. Current evidence supports the use of MBS in adolescents. Ongoing and future studies will provide 10-year outcomes and assist in the refinement of multimodal pathways incorporating MBS for the treatment of severe childhood obesity.

scholarly journals The Effectiveness of Reminiscence Therapy on Alleviating Depressive Symptoms in Older Adults: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuo Liu ◽  
Fan Yang ◽  
Yifan Lou ◽  
Wei Zhou ◽  
Feng Tong
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Older Adults ◽  
Depressive Symptoms ◽  
Meta Analysis ◽  
Current Evidence ◽  
Future Studies ◽  
Reminiscence Therapy ◽  
Group Reminiscence

Objective: Depression is one of the most common problems faced by older adults. Reminiscence therapy, defined as using the recall of past events, feelings, and thoughts facilitating pleasure, is one type of psychotherapy that could alleviate depressive feelings among older adults, improve their quality of life, and help them live independently. Reminiscence therapy originated from geriatric psychiatry, and is an effective non-pharmacological intervention that could be structured or unstructured and be conducted individually or in a group. The current systematic review was designed to summarize and review existing evidence on the effect of reminiscence therapy on depression in older adults.Methods: We conducted a systematic review from January 2000 to Mar 2021 using 10 electronic databases in English and Chinese languages, including Medline, Embase, Cinahl, PsychInfo, Cochrane, Web of Science, Google Scholar, Science Direct, CNKI, and WANFANG. We excluded studies that didn't use randomized controlled trials (RCT) from the meta-analysis. The selected studies were scored using the Cochrane Risk of Bias tool. The RevMan 5.0 was used in subgroup analysis depending on how the interventions were classified.Results: We extracted 527 studies based on keyword searches, of which 10 RCTs met inclusion criteria were included in the meta-analysis. The meta-analysis yielded high heterogeneity, and the analyses of significant subgroups showed that reminiscence therapy has a significant effect on relieving depressive symptoms in older adults. Reminiscence therapy benefits older adults with chronic illness and those on antidepressants as well. The effect and cost-effectiveness of group reminiscence therapy were higher than individual reminiscence therapy. And some specific types of group reminiscence therapy have a significant effect on improving depression and secondary outcomes, including life satisfaction. Although the effectiveness of structured and unstructured group reminiscence on depression has no significant differences according to current evidence, the structured therapy is more replicable, generalizable, and user-friendly due to its detailed protocol for new therapists. Furthermore, reminiscence therapy is more effective for older women and older adults with more severe depressive symptoms.Conclusion: Reminiscence therapy significantly increased older adults' remission from depression and quality of life immediately after the intervention. However, the evidence-based protocol and implementation of reminiscence interventions need to be further developed and standardized to facilitate global use. Moreover, it remains unclear on the long-term effect of reminiscence therapy. Based on the limitations of the current study, more rigorous evidence is needed from studies with large sample sizes, RCT design, and longer follow-up periods. Future studies could also explore the effect of different types of reminiscence therapy. Furthermore, qualitative data should be included to better understand older adults' narrative and experiences with reminiscence therapy. Future studies could also investigate the impact of reminiscence therapy on older relatives as a part of outcome measure to explore the efficacious mechanism of reminiscence therapy in alleviating older adults' depressive symptoms.

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