TEST QUESTION CRITICAL APPRAISAL OF BIOMEDICAL PUBLICATION
1. Given: The third paragraph of the introduction from Busso et al. starts with a
statement about atherosclerosis development in early life as the underlying cause
of ischemic cardiovascular disease. This statement is based on a research article
from Napoli et al. (ref 4). As a critical scientist you are interested in the relation
between early atherosclerosis and cardiovascular diseases. Below you find several
passages from the report by Napoli et al.
Question: Which answer option is the passage that Busso et al. most likely refers
to, in order to sustain their statement?
- The recruitment of circulating monocytes into the vascular intima and their
subsequent transformation into macrophage/ foam cells are key elements of
the initiation of atherosclerosis.
- In vivo evidence for the atherogenicity of OxLDL was provided by the fact that
several powerful antioxidants, e.g. probucol, butylated hydroxytoluene, and
diphenyl-phenylene- diamine, significantly reduced progression of
atherosclerosis in rabbits (9-11), primates (12), and mice (13).
- LDL oxidation and formation of fatty streaks occurs already during fetal
development, and both phenomena are greatly enhanced by maternal
hypercholesterolemia. The fact that in very early lesions LDL and Ox-LDL are
frequently found in the absence of monocyte/macrophages, whereas the
opposite is rare, suggests that intimal LDL accumulation and oxidation
contributes to monocyte recruitment in vivo.
- Lipid peroxidation products generated during LDL oxidation are chemotactic
for both monocytes and T cells, and inhibit the motility of macrophages, thus
trapping them in the intima. In addition, even minimally modified LDL (i.e.,
LDL oxidized to an extent that does not suffice for recognition by scavenger
receptors) may enhance expression of adhesion molecules and cytokines by
endothelial cells
2. Given: Consider the empirical cycle and the following sentence from the article by
Busso et al: "Taking into account the low levels of vitamin E detected in
newborns from human growth restricted pregnancies [19, 20] and the reduction
of oxidative stress by vitamin E in placenta of hypercholesterolemic rab [21], we
also analyzed whether dietary supplementation with vitamin E could prevent
growth restriction in fetuses from HC-fed females." Question: Which phase from
the empirical cycle illustrates the sentence best?
3. Given: in Figure 3 of the Busso et al. article the authors measured intrauterine
growth. Question: Which answer option provides the best description of the
importance of figure 37
- E15.5 fetuses retrieved from dams periconceptionally fed with the HC diet
weighed similar to fetuses from chow-fed mice [382 22 mg (11 fetuses)
versus 393 22 mg (e = 24 fetuses), resp., P 0.58 Student's r-test).
- Whereas newborns or term fetuses from hypercholesterolemic rabbits and
mice were previously shown to exhibit lower weights than control animals [13,
24], to our knowledge this is the first evidence describing fetal growth
, restriction associated with high maternal cholesterol levels during early stages
of gestation.
- Feeding the HC diet before and during pregnancy induced severe
hypercholesterolemia, essentially due to accumulation of non-HDL
lipoproteins, in the endogenously hypercholesterolemic LDLR KO females [22]
(7- and 8-fold at E15.5 and E18.5, resp.)
- Among the various genetically modified mice that have contributed greatly to
progress in the field of dyslipidemia [51], the LDLR KO mice exhibit a
lipoprotein pro le that is very similar to the human normal profile [52].
4. Question: What is the primary outcome measure of the study by Busso et al.7
- placental development
- fatty streaks in aortic root
- fetal growth
- fetal plasma cholesterol
- maternal plasma cholesterol
5. Given: Busso et al. performed a histological analysis of the placenta's of pregnant
LDLR-KO mice (Figure 2). Image that the authors had not measured placental
histology, but other results were exactly the same. Question: What would be the
most important limitation of the study outcome when placental histology would
be left out?
- it would lead to attrition blas
- it would not alter the conclusions of the study
- it would jeopardize the entire study, because placental histology is an
independent variable
- It would be unclear whether the reduced weight of the embryos was due to
placental alterations
6. Given: Figure 1b of the Busso et al. study shows FPLC profiles in pregnant mice.
Question: What is the major limitation of this figure?
- this figure shows only cholesterol content in lipoproteins
- cholesterol levels are below detection levels
- results from only 1 mouse per condition are presented
- only 40 fractions are measured
7. Given: Busso et al. measured plasma cholesterol levels from pregnant LDLR-KO
mice. Question: What is the most likely reason for measuring plasma cholesterol
- because it will lower the risk for performance bias
- because it demonstrates the effect of the high-cholesterol diet
- because it is a baseline measurement for predicting overweight in these mice
- because it is an important independent variable
8. Given: The fifth paragraph of the introduction from Busso et al, refers to a several
studies regarding LDLR-KO mice. Question: What is the most important alm of
the authors with this paragraph?
- to describe all the empirical cycles that have led to this study
- to provide an empirical basis for the formulated study aim
- to demonstrate the importance of the research topic
- to demonstrate the expertise of the authors
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