Leber hereditary optic neuropathy (LHON) is a maternally inherited form of central vision loss associated with mitochondrial DNA point mutations that affect the ND subunits of complex I.
Objective
To elucidate the bioenergetic consequences of complex I dysfunction in LHON.
Design
The biochemical phenotypes of LHON mutations have been investigated using the transmitochondrial cytoplasmic hybrid (cybrid) cell model derived from the osteocarcoma parental cell line 143B.TK−.
Setting
Research laboratories at neuroscience and biochemistry departments at the University of Bologna, Scientific Institute “E. Medea,” and University of College Medical School.
Participants
Fibroblast cell lines were obtained from patients affected with LHON, as defined by the presence of 1 pathogenic mutation, and from healthy volunteers as controls to construct cybrid cell lines.
Main Outcome Measures
Complex I (glutamate-malate)– and complex II (succinate)–dependent adenosine triphosphate (ATP) synthesis, their respective respiratory rates, and total cellular ATP content were investigated using digitonin permeabilized cybrid cells. Multiple cybrid cell lines were constructed, introducing into osteosarcoma-derived rho0cells either wild-type or LHON mutant mitochondria carrying each of the 3 common mutations at positions 11778/ND4, 3460/ND1, and 14484/ND6.
Results
All 3 LHON mutations impaired ATP synthesis and the respiratory control ratio driven by complex I substrates. In contrast, succinate-driven ATP synthesis, respiration rates, and respiratory control ratios were not affected. However, the defective ATP synthesis with complex I substrates did not result in reduced ATP cellular content, indicating a compensatory mechanism.
Conclusions
The LHON pathogenic mutations profoundly impair complex I–dependent synthesis of ATP, providing a common biochemical feature that may play a major role in LHON pathogenesis. Stratification of the results by mutation suggests that the 11778/ND4mutation may induce an uncoupling of cybrid respiration, whereas the other 2 mutations impair the oxygen consumption rate.
Purpose. To report on the preliminary results of an Italian project on the implementation of an ICF-based protocol for providing public services and benefits for persons with disabilities.
Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect. Inclusion criteria regarded children/adolescents diagnosed with cancer on treatment or <1 year off therapy. The internal consistency was assessed using Cronbach's α, and the floor-ceiling effects were calculated through percentage. This study involved 217 participants with heterogeneous neoplasm conditions. Internal consistency was good, with a Cronbach's α of 0.989. Floor-ceiling effect analysis reveals that several items obtained a dichotomous scoring distribution in each of the five sub-scales of the GMFM-88. This can be explained by the heterogeneous clinical characteristics of the target population. The preliminary validation of GMFM-88 in a group of children/adolescents affected by cancer suggests that some items are not able to discriminate between different gross motor function levels, and therefore it does not represent an informative tool to measure gross motor function in children with cancer. Future research is needed to define which ones could be more useful for clinical practice.
Purpose. To present the preliminary results of training courses on the International Classification of Functioning, Disability and Health (ICF) prepared by Italian WHO FIC CC and to report on strategies for ICF dissemination among primary health care (PHC) workers in Mavalane Health Area, Maputo, Mozambique.Methods. A participant-observer description of ICF principles introduction and development of ICF-CY modified checklists in Mavalane health area according to a person-environment interaction classification (PEIC) tree.Results. The first ICF courses were held at Mavalane hospital and involved 25 health workers and 24 members of the health committee acting in the local area. The courses were prepared having as a framework the theoretical principles of the UN Convention of rights of persons with disabilities and the ICF bio-psychosocial model. The trainers adapted and modified the course materials to increase the applicability of the protocol to the cultural and social reality of Mozambique, eventually applying the person-environment interaction classification (PEIC) tree.Conclusions. The very first phase of this project indicates that the use of the ICF checklist is feasible also in a crowded and busy environment like some PHC units of a developing country. However, data collection require a simpler and lighter to use data compilation tool. The proposed new checklist, which includes a PEIC tree, makes easier the compilation and the collection of data.
