Safety issues and harmful pharmacological interactions of nutritional supplements in Duchenne muscular dystrophy: considerations for Standard of Care and emerging virus outbreaks

At the moment, little treatment options are available for Duchenne muscular dystrophy (DMD). The absence of the dystrophin protein leads to a complex cascade of pathogenic events in myofibres, including chronic inflammation and oxidative stress as well as altered metabolism. The attention towards dietary supplements in DMD is rapidly increasing, with the aim to counteract pathology-related alteration in nutrient intake, the consequences of catabolic distress or to enhance the immunological response of patients as nowadays for the COVID-19 pandemic emergency. By definition, supplements do not exert therapeutic actions, although a great confusion may arise in daily life by the improper distinction between supplements and therapeutic compounds. For most supplements, little research has been done and little evidence is available concerning their effects in DMD as well as their preventing actions against infections. Often these are not prescribed by clinicians and patients/caregivers do not discuss the use with their clinical team. Then, little is known about the real extent of supplement use in DMD patients. It is mistakenly assumed that, since compounds are of natural origin, if a supplement is not effective, it will also do no harm. However, supplements can have serious side effects and also have harmful interactions, in terms of reducing efficacy or leading to toxicity, with other therapies. It is therefore pivotal to shed light on this unclear scenario for the sake of patients. This review discusses the supplements mostly used by DMD patients, focusing on their potential toxicity, due to a variety of mechanisms including pharmacodynamic or pharmacokinetic interactions and contaminations, as well as on reports of adverse events. This overview underlines the need for caution in uncontrolled use of dietary supplements in fragile populations such as DMD patients. A culture of appropriate use has to be implemented between clinicians and patients’ groups

Developing a Conceptual Design Engineering Toolbox and its Tools

In order to develop a successful product, a design engineer needs to pay attention to all relevant aspects of that product. Many tools are available, software, books, websites, and commercial services. To unlock these potentially useful sources of knowledge, we are developing C-DET, a toolbox for conceptual design engineering. The idea of C-DET is that designers are supported by a system that provides them with a knowledge portal on one hand, and a system to store their current work on the other. The knowledge portal is to help the designer to find the most appropriate sites, experts, tools etc. at a short notice. Such a toolbox offers opportunities to incorporate extra functionalities to support the design engineering work. One of these functionalities could be to help the designer to reach a balanced comprehension in his work. Furthermore C-DET enables researchers in the area of design engineering and design engineers themselves to find each other or their work earlier and more easily. Newly developed design tools that can be used by design engineers but have not yet been developed up to a commercial level could be linked to by C-DET. In this way these tools can be evaluated in an early stage by design engineers who would like to use them. This paper describes the first prototypes of C-DET, an example of the development of a design tool that enables designers to forecast the use process and an example of the future functionalities of C-DET such as balanced comprehension

Year in review 2006: Critical Care – resource management

As health care resources become increasingly constrained, it is imperative that intensive care unit resources be optimized. In the years to come, a number of challenges to intensive care medicine will need to be addressed as society changes. Last year's Critical Care papers provided us with a number of interesting and highly accessed original papers dealing with health care resources. The information yielded by these studies can help us to deal with issues such as prognostication, early detection and treatment of delirium, prevention of medical errors and use of radiology resources in critically ill patients. Finally, several aspects of scientific research in critically ill patients were investigated, focusing on the possibility of obtaining informed consent and recall of having given informed consent

The role of patient involvement when developing therapies

The drug development process is a long and arduous one, especially for rare diseases. Patient and patient representatives can and should be involved in this process from an early stage, since they have the perspective of living with a disease on a daily basis and can best identify which symptoms are the largest burden and which benefits would be more important to them. In this perspective, we outline how patients can be involved optimally in drug development. We outline success factors such as finding the right partners, bilateral education, having realistic expectations, and an open and honest dialog with all stakeholders.Functional Genomics of Muscle, Nerve and Brain Disorder

Translational and Regulatory Challenges for Exon Skipping Therapies

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.status: publishe

Mast cells, eosinophils and IgE-positive cells in the nasal mucose of patients with vasomotor rhinitis - An immunohistochemical study

Vasomotor rhinitis (VMR) is a disorder of unknown pathogenesis. Forty patients with VMR were carefully selected on the basis of inclusion and exclusion criteria proposed by Mygind and Weeke. Nasal biopsy specimens were taken in the patient group as well as in a group of ten controls. Brush cytology was also taken in the VMR group. Inflammatory cells were identified and counted in the nasal mucosa, with the use of immunohistochemical techniques and a panel of monoclonal antibodies. Eosinophils were studied with the use of BMK13, EG2, and Giemsa. Mast cells were studied with anti-chymase (B7), anti-tryptase (G3) and toluidine blue. Sections were stained with IgE as well. There was no significant difference in the number of eosinophils, mast cells and IgE-positive cells between the two groups. Additionally, in contrast with other reports, in sections that were double-stained with anti-chymase and anti-tryptase, single chymase-positive cells were found

Связи изменений среднемесячных ОСО над Антарктикой и площади теплого тропического бассейна Тихого океана при современном потеплении климата

Объектом данного исследования выбраны изменения распределения среднемесячных значений ОСО над Антарктикой, а также площади ТТБ в западном полушарии. Предметом исследования есть изменения статистических связей между указанными процессами, происходившими за период современного потепления климата. Целью работы есть выявление их связей, которые на протяжении периода современного потепления климата усиливались устойчиво и ныне являются значимыми

Typha latifolia paludiculture effectively improves water quality and reduces greenhouse gas emissions in rewetted peatlands

Paludiculture, the cultivation of crops on wet or rewetted agricultural peatlands, sustainably integrates productive land use with the provision of multiple ecosystem services. Paludiculture crops thrive under waterlogged conditions that stimulate nitrogen (N) and phosphorus (P) removal from soil and water and convert serious drainage-induced carbon (C) losses to C sequestration. Nutrient uptake by paludicrops can prevent mobilisation after rewetting and provide opportunities for purification of nutrient-rich water. Uncertainty remains, however, if and to what extent N loading and a subsequent increase in biomass productivity affect nutrient cycling as well as emissions of the potent greenhouse gases methane (CH4) and nitrous oxide (N2O). In this study, we use mesocosms with rewetted peat to investigate the effect of different N sources in surface water on biomass production of Typha latifolia, a typical paludiculture crop, and the emissions of CH4 and N2O. Organic (Azolla filiculoides; urea) or mineral (KNO3 ; NH4NO) N was supplied either a single time (steady state) or repeatedly (pulse) to simulate a total surface water load of 150 kg N ha(-1) . We found that N stimulated aboveground and belowground biomass production and nutrient uptake by T. latifolia. These effects were absent in Azolla treatments. Whereas after two months CH4 emissions arose to substantial amounts (> 10 mg CH4 m(-2) day(-1)) in unvegetated mesocosms loaded with organic N, they remained very low (<1 mg CH4 m(-2) day(-1)) in vegetated mesocosms, despite the labile C pool in the extensive belowground biomass and organic N loading. Overall, N2O emissions were close to zero and were only detected episodically after NO(3)(- )loading, irrespective of plant presence. Our findings support that T. latifolia as a paludicrop effectively removes various forms of N and P when harvested, and strongly mitigates CH4 emission after the rewetting of agricultural peat soils compared to unvegetated conditions