TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Obstructive sleep apnea (OSA) is a common disorder characterized by chronic intermittent hypoxia (CIH). OSA is prevalent in obese subjects and is associated with endothelial dysfunction and cardiovascular disorders. We tested the hypothesis that the deleterious effects of IH could be further modulated by diet-induced obesity.', 'Thirty adult (8-10 weeks) male C57BL/6J mice were divided into four groups. Mice were subjected to CIH or intermittent air (IA) for 12h a day and fed either a high fat (HF) or a low fat control diet (CD) for 6weeks. We analyzed endothelial function using a wire myograph, and measured markers of oxidative stress (plasma malondialdehyde (MDA) and total antioxidant capacity (TAC)) using colorimetrical assays. We also measured C-reactive protein (CRP) using ELISA and endothelial nitric oxide (eNOS) gene expression using real time PCR.', 'Stimulated endothelial dependent dilation was significantly impaired only in the group fed high fat diet and subjected to CIH (Emax: HFIH 782%, p<0.0001) when compared to the other groups (Emax: HFIA 950.7%, CDIH 942%, CDIA 971%). Also basal endothelial dependant dilation was attenuated in the HFIH group compared to the HFIA group (Emax: HFIH: 17910% vs. HFIA: 14911% in the presence of L-NAME). Levels of MDA were elevated in the CDIH group when compared to CDIA (0.680.04 vs. 0.410.03 M, p<0.05) but were greatest in the HFIH group (0.830.08 M, p<0.05). However, there was no significant increase in MDA levels in the HFIA group (0.450.03 M, p=NS) when compared to all other groups. Similar effects were observed with CRP levels; CRP levels were significantly higher in the CDIH group compared with intermittent air (10.390.38 vs. 8.700.21 g/ml, p<0.05) but the HFIH had the greatest levels of CRP (11.870.31 g/ml, p<0.05). In the HFIA group, CRP levels were not elevated (9.960.37 g/ml, p=NS). Nevertheless, total antioxidant capacity and eNOS gene expression were not significantly different in the groups.\Question: Does chronic intermittent hypoxia cause endothelial dysfunction in a mouse model of diet-induced obesity?

SOLUTION: CIH caused endothelial dysfunction in mice fed an obesogenic diet. Inflammation and oxidative stress were increased in CIH and an obesogenic diet exacerbated these effects.

PROBLEM: Context: To investigate whether preconditioning with high mobility group box 1 protein (HMGB1) could reduce myocardial ischemia-reperfusion (I/R) injury.', 'Infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) were assessed. HMGB1 preconditioning reduced significantly the infarct size induced by I/R. The LDH, CK, TNF- and IL-6 levels were significantly decreased by HMGB1 preconditioning compared to those in the I/R group.\Question: Does preconditioning with high mobility group box 1 protein protect against myocardial ischemia-reperfusion injury?

SOLUTION: The present study suggested that preconditioning with HMGB1 could induce HMGB1 tolerance and protect against myocardial I/R injury.

PROBLEM: Context: To elucidate the retinal dysfunction and the molecular basis of posterior polymorphous corneal dystrophy (PPCD) associated with macular dystrophy, both inherited in a dominant manner through a three-generation family.', 'Ophthalmologic examinations including slit lamp examination, visual acuity tests, fundus visualization by scanning laser ophthalmoscopy, fluorescein angiography, color vision tests, electro-oculography, photopic and scotopic electroretinography (ERG) according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocols, and oscillatory potential (OP) recordings were conducted on affected family members. Corneal button from one affected patient was examined by transmission electron microscopy. All exons and intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by polymerase chain reaction and sequenced.', 'The presence of endothelial cells that have epithelial-like features with multiple layers, desmosomal junctions, and microvillous projections supports the diagnosis of PPCD. Sequence analysis indicated that the H244R variant in the VSX1 segregated with corneal and macular disease phenotypes in this family. Electrophysiologic studies indicated normal scotopic ERG findings, decreased amplitude of the photopic b-wave, photopic OP2 and OP3 barely recordable with a preserved OP4 amplitude, and variably decreased 30-Hz flicker amplitude.\Question: Is h244R VSX1 associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family?

SOLUTION:
The human VSX1 is required for cone ON bipolar cell function but not for rod and cone OFF bipolar cells, giving a unique example of such a selective heritable retinal defect in humans. Furthermore, the authors provide the first clinical support for a new alternative role of VSX1 in cone biology, probably similar to that proposed for its goldfish ortholog during retinal differentiation.