Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel. Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. Recent next-generation sequencing methods are now identifying multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.", "In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1 gene identified two different missense mutations: c.14256 A >C polymorphism in exon 98 and c.14693 T >C in exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed because patient's daughter, mother and sister carried only the exon 98's mutation, a synonymous variant that was subsequently found in the frequency of 013-0,05 of alleles. Further next generation sequencing study of the whole RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and 8 polymorphisms in heterozygosis.
Answer: Considering that patient's relatives showed no pathologic phenotype, and the phenotype presented by the patient is within the range observed in other central core disease patients with the same mutation, it was concluded that the c.14256 A >C polymorphism alone is not responsible for disease, and the associated additional silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The case described above illustrates the present reality where new methods for wide genome screening are becoming more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in patients and their families.
Do silent polymorphisms in the RYR1 gene modify the phenotype of the p.4898 I > T pathogenic mutation in central core disease : a case report?

Context: Is weight-training exercise intervention harmful to women with or at risk of breast cancer-related lymphoedema?', 'Systematic review with meta-analysis of randomised trials.', 'Women with or at risk of breast cancer-related lymphoedema.', 'Progressive weight-training exercise.', 'The primary outcomes were severity (volume difference) and incidence of arm lymphoedema. Secondary outcomes included muscle strength of the upper and lower limbs, quality of life and body mass index.', 'Eleven studies from eight trials involving 1091 women were included. Weight-training exercise of low to moderate intensity with relatively slow progression significantly improved the upper limb strength (SMD 0.93, 95% CI 0.73 to 1.12) and lower limb strength (SMD 0.75, 95% CI 0.47 to 1.04) without increasing the arm volume (SMD -0.09, 95% CI -0.23 to 0.05) or incidence of breast cancer-related lymphoedema (RR 0.77, 95% CI 0.52 to 1.15). No significant effects were noted for body mass index (SMD -0.10, 95% -0.31 to 0.11). Some aspects of quality of life may improve with weight training. PARTICIPANTS in all trials used pressure garments and received supervision; no trials used high-intensity weight training.
Answer: Weight training appears to be safe and beneficial in improving limb strength and physical components of quality of life in women with or at risk of lymphoedema. Pressure garments, supervision and limiting the intensity of the weight training may each be important, but this could not be confirmed with this review.
Is weight training harmful for women with breast cancer-related lymphoedema : a systematic review?

Context: Ninety-six male adult CD-1 mice were randomly divided into sham, spinal cord injury (SCI)+vehicle, and SCI+IPA-3 groups. Expression of matrix metalloproteinase (MMP)-2 and MMP-9, production of tumor necrosis factors (TNF)- and interleukin (IL)-1, tissue edema, blood-spinal cord barrier penetrability, neural cell apoptosis, and neurological function recovery were measured.', 'The aim of the study was to evaluate the effect of specific inhibition of p21-activated kinase 1 (PAK1) by IPA-3 on SCI and the underlying mechanisms thereof.', 'SCI is a devastating clinical condition that may result in long-lasting and deteriorating functional deficits. The major goal of SCI treatment is to limit the development of secondary injury. IPA-3, a PAK1 inhibitor, exhibited neuroprotection against secondary damage after traumatic brain injury and subarachnoid hemorrhage (SAH).', 'MMP-2, MMP-9, and cleaved caspase-3 expression were assessed by Western blot. Inflammatory cytokines TNF- and IL-1 were detected by enzyme-linked immunosorbent assay (ELISA). The blood-spinal cord barrier disruption was measured by water content and Evans blue extravasation of the spinal cord. Neuronal apoptosis was evaluated by Nissl staining and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay. The locomotor behavior of hind limb was evaluated by Basso Mouse Scale (BMS) at 1, 3, 7, 14, and 28 days post-injury.', 'Compared with SCI+vehicle mice, IPA-3 treatment showed decreased p-PAK1, MMP-2, MMP-9, cleaved caspase-3, TNF-, and IL-1 expression. Moreover, inhibition of PAK1 by IPA-3 reduced spinal cord water content and Evans blue extravasation, increased neuronal survival, and reduced TUNEL-positive cells at 24 hours after SCI. Furthermore, IPA-3 improved spinal cord functional recovery 7 days after SCI.
Answer: Inhibition of PAK1 by IPA-3 promoted recovery of neurological function, possibly by downregulating the expression of MMP-2, MMP-9, TNF-, and IL-1. Our data suggest that PAK1 may be a potential therapeutic target in patients with SCI.
Does inhibition of p21-Activated Kinase 1 by IPA-3 promote Locomotor Recovery After Spinal Cord Injury in Mice?