Furthermore, mutations in mitochondrial genes have been implicated in exercise intolerance in humans [ 21].
Furthermore, mutations in mitochondrial genes have been implicated in exercise intolerance in humans [ 12] (see Table 1).
Hypothalamic, mitochondrial and sympathetic dysfunction may also be implicated in exercise and fatigue responses in CFS patients [ 3, 15, 16].
One of the most challenging conundrums for the sports cardiologist is the interpretation and management of profound repolarisation changes, notably deep T-wave inversions, which are also common manifestations of disorders implicated in exercise-related SCD among young athletes.
140 Finally, SCN5A has been implicated in exercise-induced polymorphic ventricular arrhythmias, with the recent identification of a novel missense mutation in a highly conserved region of the gene in a large family with a CPVT phenotype.
Whilst the impairment in cardiac output to meet peripheral oxygen demands during exercise largely contributes to the reduction in exercise capacity [ 7], skeletal muscle dysfunction may also be implicated in the exercise limitation experienced by individuals with PAH [ 7- 10].
Muscle-specific overexpression of PGC1α leads to increased endurance performance (4), whereas decreased expression has been implicated in reduced exercise tolerance, chronic inflammation, and mitochondrial myopathy (10, 20).
For example, focal adhesion kinase has been implicated in regulating exercise-induced muscle growth (6, 7) and disuse atrophy (8).
Moreover, sub-optimal nutrition and hydration during periods of extreme exertion is clinically relevant, having been implicated in exacerbating exercise-induced immunodepression, impaired repair and healing, cytokine dysfunction associated with chronic fatigue, rapid onset microcytic anaemia, exercise-induced rhabdomyolysis, and exertional heat illnesses [3, 8 13].
The high mobility group box 1 (HMGB1) is one of the HMGB superfamily members which was also shown to be implicated in inflammation exercising cytokine like functions [ 83].
Yet for most of those close to Cáceres, and for long-term observers of Honduras, the security forces of Honduras are implicated in the normal exercise of impunity that has only been interrupted here due to the higher visibility that Cáceres achieved internationally.
