TASK DEFINITION: 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.
PROBLEM: Context: Nagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK.', 'To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK.', 'We analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing.', 'We identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK.
Answer: These data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7.

SOLUTION: Does highly prevalent SERPINB7 founder mutation cause pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis?

PROBLEM: Context: The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.', 'The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.', 'The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed.', 'Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.
Answer: The synergism between TGF-beta1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.

SOLUTION: Do tacrolimus and TGF-beta act synergistically on the generation of Langerhans cells?

PROBLEM: Context: This study was conducted to determine if there was an increase in the urinary excretion of fluoride, after the use of fluoride mouth rinses in children.', 'The sample consisted of 58 children aged 5-8 years, randomly selected, residents in non-fluoridated water areas. Urine samples were collected prior to mouthwash and also 2 hours after use. The control sample, which received no treatment, consisted of 16 children of equivalent age and from the same community. Urinary excretion of fluoride was analysed by determining the pH, creatinine, F- ion and fluoride (mg)/creatinine (g) (F/Cr) ratio in urine. Results In the studied sample, the mean F/Cr ratio before fluoride mouth rinse was 0.26 mg/g and it rose to 1.58 mg/g 2 hours after mouth rinse. This difference of 1.33 mg/g was statistically highly significant (p<.001). In the control group no significant changes occurred. The average 2 hours afterward F/Cr ratios were 0.29 and 0.27 respectively (p=0.426).
Answer: After the use of a fluoride mouthwash, in children, there is a statistically significant increase of fluoride ion in urine, which can be attributed to the application of this product.

SOLUTION:
Does renal excretion of fluoride after fluoride mouth rinse in children?