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Abstract: Lymphoedema–distichiasis syndrome (LDS, OMIM #153400) is a genetic disorder with an autosomal dominant pattern of inheritance caused by mutations in the FOXC2 gene. Affected individuals typically present with lower extremity lymphoedema and distichiasis. The most common types of mutations in FOXC2 gene include small deletions and insertions, but duplications, duplications-insertions, missense and nonsense mutations were also found. Herein, we describe three generations of a family diagnosed with LDS caused by a new mutation in the FOXC2 gene. This mutation is a frameshift due to a deletion of two nucleotides (CC) in C repeats between C586 and C591. This mutation leads to protein truncation as a result of an earlier insertion of a stop codon. To the best of our knowledge, this is the first description of this mutation in the literature and could be coupled with an atypical lymphoscintigram. [Copyright &y& Elsevier]

The authors evaluated the impact of different dose of metformin on NO (nitric oxide) production in subjects with pre-diabetes. The metformin-naïve patients from one Diabetic Center with newly diagnosed pre-diabetes, without cardio-vascular diseases, were randomized (based on the identification number, individual for each inhabitant in the country) for treatment with different doses of metformin (group A 3 × 500 mg, group B 3 × 1000 mg) for 12 weeks. Then, the subjects from group B were switched to dose 3 × 500 for the last 3 weeks. The wide panel of L -arginine/NO pathway metabolites concentrations was assessed using the liquid chromatography-mass spectrometry technique. Between October 2017 and December 2018, 36 individuals were initially randomized to intervention groups. The study was completed with 25 subjects: 14 patients in group A, 11 in group B; also 11 healthy volunteers were recruited. There was no difference between participants with pre-diabetes and healthy volunteers as regards the baseline characteristics except for fasting glucose and fatty liver. The decrease of L -citrulline concentration only was reported for treatment groups during the intervention period, with no change for the other NO-production related substances. It was the first study on the in vivo release of NO in humans with different metformin doses in patients with pre-diabetes. Metformin did not seem to increase NO production measured by the citrulline plasma levels, irrespective of the dose. The citrulline concentration change might indicate the drug impact on the condition of the enterocytes. [Display omitted] • The metformin has no impact on NO production. • Even the highest accepted dose of metformin does not change the results. • This observation on humans supports the previous ones conducted on mice. • The change in citrulline level was observed while metformin was taken. [ABSTRACT FROM AUTHOR]

• The gap between blood sample taking and its centrifugation can have a potential impact on the metformin concentration result. • Two hours gap between taking blood and centrifugation has no impact on the metformin serum concentration. • Although the LC/MS method was used, our findings can be extended to all types of techniques dedicated to assessing metformin concentration. This is an informative article which can help research providers to arrange and conduct studies dedicated to the assessment of metformin serum concentrations. If there is a problem with coordination of sample preparation and it is necessary to measure metformin concentration, two hours gap between blood drain and centrifugation has no impact on the results. [ABSTRACT FROM AUTHOR]