233 research outputs found
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion
A female infant of nonconsanguineous Indian parents presented at 4 months with a hypoglycemic convulsion. Further episodes of hypoketotic hypoglycemia were associated with inappropriately elevated plasma insulin concentrations. However, unlike other children with hyperinsulinism, this patient had a persistently elevated blood spot hydroxybutyrylcarnitine concentration when fed, as well as when fasted. Measurement of the activity of L-3-hydroxyacyl-CoA dehydrogenase in cultured skin fibroblasts with acetoacetyl-CoA substrate showed reduced activity. In fibroblast mitochondria, the activity was less than 5% that of controls. Sequencing of the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) genomic DNA from the fibroblasts showed a homozygous mutation (C773T) changing proline to leucine at amino acid 258. Analysis of blood from the parents showed they were heterozygous for this mutation. Western blot studies showed undetectable levels of immunoreactive SCHAD protein in the child's fibroblasts. Expression studies showed that the P258L enzyme had no catalytic activity. We conclude that C773T is a disease-causing SCHAD mutation. This is the first defect in fatty acid beta -oxidation that has been associated with hyperinsulinism and raises interesting questions about the ways in which changes in fatty acid and ketone body metabolism modulate insulin secretion by the beta cell. The patient's hyperinsulinism was easily controlled with diazoxide and chlorothiazide
Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: A scoping review
The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hemophilia may require switching of clotting factor concentrates due to a variety of factors, but there have been perceived risks associated with switching, such as inhibitor development or suboptimal protection due to inadequate dosing while titrating treatment. Studies that look at patients switching from one clotting factor concentrate to another are categorized in terms of their primary and/or secondary objectives, notably biosimilarity and comparative pharmacokinetic studies and inhibitor development studies. Research on how best to switch concentrates with respect to dosing regimen are lacking, and currently a trial-and-error approach is used for dosing the new factor concentrate. In the future, studies looking at the predictability of pharmacokinetics (PK) of a new factor concentrate based on individual PK knowledge of the original factor concentrate may offer clinical benefit by providing a safer switching approach and protocol
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Mindfulness for the self-management of negative coping, rumination and fears of compassion in people with cancer: An exploratory study
Background
Cancer and its treatments have the potential to significantly impact mental health, provoking feelings of anxiety, depression, and distress, which can last long after treatment is over. One of the most rapidly emerging influences in the healthcare field is mindfulness-based interventions (MBIs), which are designed to cultivate present moment awareness, attentional flexibility, compassion and acceptance, to reduce physical and psychological distress. However, there is limited research into the efficacy of MBIs or disease specific MBIs in shifting negative coping, ruminative thinking and fears of compassion as primary outcomes in individuals with cancer.
Aims
This exploratory study was designed to evaluate inter- and intra-individual change in the management of negative coping, rumination and fears of compassion, following a cancer-specific mindfulness-based intervention.
Methods and Results
A single group, non-experimental, repeated measures study of 22 participants across six cancer care centres explored the efficacy of an 8-week Mindfulness-Based Cognitive Therapy for Cancer (MBCT-Ca) course. The Reliable Change Index (RCI) examined reliable clinical improvement, deterioration, or no change in individuals on the Mental Adjustment to Cancer Scale (MACS), the Ruminative Responses Scale (RRS) and the Fears of Compassion Scale (FCS). About 82% of participants (n = 18) saw an improvement in at least one measure. A significant decrease in primary outcome scores was observed in negative coping, ruminating and fears of self-compassion. There were significant correlations between the fear of self-compassion and depressive ruminating, fear of accepting compassion from others and showing it to others pre and post intervention.
Conclusion
Our findings indicate that the MBCT-Ca programme may significantly reduce negative coping, ruminating and fears of self-compassion improving psychological health and wellbeing in cancer survivors
The Union and Médecins Sans Frontières approach to operational research.
Operational research (OR) has become a hot topic at national meetings, international conferences and donor fora. The International Union Against Tuberculosis and Lung Disease (The Union) and Médecins Sans Frontières (MSF) Operational Centre Brussels strongly promote and implement OR with colleagues in low- and middle-income countries. Here we describe how the two organisations define OR, and explain the guiding principles and methodology that underpin the strategy for developing and expanding OR in those countries. We articulate The Union's and MSF's approach to supporting OR, highlighting the main synergies and differences. Then, using the Malawi National Tuberculosis Control Programme as an example, we show how OR can be embedded within tuberculosis control activities, leading to changes in policy and practice at the national level. We discuss the difficult, yet vitally important, issue of capacity building, and share our vision of a new paradigm of product-related training and performance-based OR fellowships as two ways of developing the necessary skills at country level to ensure research is actually performed. Finally, we highlight the need to consider and incorporate into practice the ethical components of OR. This is a key moment to be involved in OR. We are confident that in partnership with interested stakeholders, including the World Health Organization, we can stimulate the implementation of quality, relevant OR as an integral part of health service delivery that in turn will lead to better health for people, particularly for those living in the poorer parts of the world
Measuring health-related quality of life measures in children: lessons from a pilot study
There is a debate in the health outcomes literature regarding who the most appropriate respondent is when assessing children’s health-related quality of life (HRQoL). In some cases, parent-proxy may be the only practical option where children are unable to self-complete an HRQoL questionnaire. However, children’s self-reported values may be preferable because HRQoL is subjective and represents the respondent own perception of health. We collected the youth version of the EQ-5D-3L as part of a feasibility study comparing psychoanalytic child psychotherapy with usual care for children aged 5-11 years with treatment resistant conduct disorders. The questionnaires were completed at baseline and 4-month follow-up by the child via face-to-face researcher administration, and by one parent as a proxy respondent. We present percentages of completion at each time-point and investigate the level of agreement between child and proxy-respondent on the child’s health. About two thirds of children (65.5%) were able to complete the EQ-5D-Y at baseline and 34.4% at follow-up. Children and primary carers were mostly concordant regarding overall child’s health. Parents reported more problems in ‘doing usual activities’ and ‘feeling worried, sad or unhappy’ and fewer problems with ‘pain’ and ‘looking after oneself’ than children did. The reports regarding ‘mobility’ were very similar between children and proxy-respondents. The assessment of quality of life by children using selfreport questionnaires is possible with the help of a face-to-face researcher, providing evidence that children should be asked to self-complete HRQoL questionnaires in trial studies
Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma
Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported in classical Hodgkin Lymphoma (cHL) that a member of the THE1B class of LTR elements acted as a promoter for the proto-oncogene and growth factor receptor gene CSF1R and that expression of this gene is required for cHL tumour survival. However, to which extent and how such elements participate in globally shaping the unique cHL gene expression programme is unknown. To address this question we mapped the genome-wide activation of THE1-LTRs in cHL cells using a targeted next generation sequencing approach (RACE-Seq). Integration of these data with global gene expression data from cHL and control B cell lines showed a unique pattern of LTR activation impacting on gene expression, including genes associated with the cHL phenotype. We also show that global LTR activation is induced by strong inflammatory stimuli. Together these results demonstrate that LTR activation provides an additional layer of gene deregulation in classical Hodgkin lymphoma and highlight the potential impact of genome-wide LTR activation in other inflammatory diseases
Language in tuberculosis services: can we change to patient-centred terminology and stop the paradigm of blaming the patients?
The words 'defaulter', 'suspect' and 'control' have been part of the language of tuberculosis (TB) services for many decades, and they continue to be used in international guidelines and in published literature. From a patient perspective, it is our opinion that these terms are at best inappropriate, coercive and disempowering, and at worst they could be perceived as judgmental and criminalising, tending to place the blame of the disease or responsibility for adverse treatment outcomes on one side-that of the patients. In this article, which brings together a wide range of authors and institutions from Africa, Asia, Latin America, Europe and the Pacific, we discuss the use of the words 'defaulter', 'suspect' and 'control' and argue why it is detrimental to continue using them in the context of TB. We propose that 'defaulter' be replaced with 'person lost to follow-up'; that 'TB suspect' be replaced by 'person with presumptive TB' or 'person to be evaluated for TB'; and that the term 'control' be replaced with 'prevention and care' or simply deleted. These terms are non-judgmental and patient-centred. We appeal to the global Stop TB Partnership to lead discussions on this issue and to make concrete steps towards changing the current paradigm
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