Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial.

AIMS: This study investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone ± metformin in patients with type 2 diabetes (T2DM). METHODS: Patients with HbA1c ≥7 and ≤10% were randomized and treated with once daily empagliflozin 10 mg (n = 165), empagliflozin 25 mg (n = 168) or placebo (n = 165) as add-on to pioglitazone ± metformin for 24 weeks. Endpoints included changes from baseline in HbA1c (primary endpoint), fasting plasma glucose (FPG) and body weight at week 24. RESULTS: Adjusted mean ± standard error changes in HbA1c were -0.6 ± 0.07% and -0.7 ± 0.07% with empagliflozin 10 mg and 25 mg, respectively, vs. -0.1 ± 0.07% with placebo (both p < 0.001). More patients with HbA1c ≥7% at baseline achieved HbA1c <7% with empagliflozin 10 mg (23.8%) and 25 mg (30.0%) vs. placebo (7.7%) (both p < 0.001). FPG decreased with empagliflozin (-0.94 mmol/l for 10 mg and -1.22 mmol/l for 25 mg) and increased with placebo (+0.36 mmol/l; both p < 0.001). Adjusted mean ± standard error changes in weight were -1.62 ± 0.21 kg and -1.47 ± 0.21 kg with empagliflozin 10 mg and 25 mg, respectively, vs. +0.34 ± 0.21 kg with placebo (both p < 0.001). Similar proportions of patients reported adverse events with empagliflozin (67.3-71.4%) and placebo (72.7%). Confirmed hypoglycaemia was reported by 1.2-2.4% of patients on empagliflozin and 1.8% on placebo. CONCLUSION: Empagliflozin 10 mg and 25 mg once daily for 24 weeks as add-on to pioglitazone ± metformin reduced HbA1c, FPG and weight and were well tolerated in patients with T2DM.

Association analysis of photoperiodic flowering time genes in west and central African sorghum [Sorghum bicolor (L.) Moench].

BACKGROUND: Photoperiod-sensitive flowering is a key adaptive trait for sorghum (Sorghum bicolor) in West and Central Africa. In this study we performed an association analysis to investigate the effect of polymorphisms within the genes putatively related to variation in flowering time on photoperiod-sensitive flowering in sorghum. For this purpose a genetically characterized panel of 219 sorghum accessions from West and Central Africa was evaluated for their photoperiod response index (PRI) based on two sowing dates under field conditions. RESULTS: Sorghum accessions used in our study were genotyped for single nucleotide polymorphisms (SNPs) in six genes putatively involved in the photoperiodic control of flowering time. Applying a mixed model approach and previously-determined population structure parameters to these candidate genes, we found significant associations between several SNPs with PRI for the genes CRYPTOCHROME 1 (CRY1-b1) and GIGANTEA (GI). CONCLUSIONS: The negative values of Tajima's D, found for the genes of our study, suggested that purifying selection has acted on genes involved in photoperiodic control of flowering time in sorghum. The SNP markers of our study that showed significant associations with PRI can be used to create functional markers to serve as important tools for marker-assisted selection of photoperiod-sensitive cultivars in sorghum.

Population structure in sorghum accessions from West Africa differing in race and maturity class.

Accounting for population structure to minimize spurious associations in association analyses is of crucial importance. With sorghum genomic sequence information being available, there is a growing interest in performing such association studies for a number of important agronomic traits using a candidate gene approach. The aims of our study were to conduct a systematic survey of molecular genetic diversity and analyze the population structure in cultivated sorghum [Sorghum bicolor (L.) Moench] accessions from West Africa. Our analysis included 219 West African cultivated sorghum accessions with differing maturity intended for a marker-trait association study. A total of 27 SSRs were used, which resulted in detection of 513 alleles. Genetic diversity estimates for the accessions were found to be high. The accessions were divided into two subgroups using a model-based approach. Our findings partly agree with previous studies in that the guinea race accessions could be distinguished clearly from other accessions included in the analysis. Race and geographical origin of the accessions may be responsible for the structure we observed in our material. The extent of linkage disequilibrium for all combinations of SSRs was in agreement with expectations based on the mating system.

Variability of phyllochron, plastochron and rate of increase in height in photoperiod-sensitive sorghum varieties.

BACKGROUND AND AIMS: West African sorghum (Sorghum bicolor) varieties are generally highly photoperiod-sensitive, which is a necessary adaptation to the variable onset date of the rainy season and the variable dates of sowing in the savannah zone. Depending on sowing date, plants can produce from 12 to >40 leaves on the main culm, with height varying from 1 m to more than 5 m. The present study aimed to better understand the complex phenology of these variables. METHODS: A 2-year series of monthly sowings of three West African sorghum varieties was conducted near Bamako, Mali. Drought stress was avoided by supplemental irrigation. Rate of initiation of primordia at the stem apex was recorded, together with rate of leaf emergence and increase in plant height. KEY RESULTS: Leaf initiation and appearance rates (plastochron(-1) and phyllochron(-1)) were constant for a given sowing date in cases where less than 20 leaves were produced (generally observed with late sowing dates). In contrast, rates were bilinear for early sowing dates, for which plants produced more than 20 leaves. The secondary rates, which occurred from the 20th leaf onwards, were only half of the initial rate. Plastochron and phyllochron showed large variations among sowing dates, and were correlated with the rate of plant height increase. The initial plastochron and phyllochron were positively correlated with soil temperature and negatively correlated with both day length and day-to-day change of day length prevailing at plant emergence, but these factors explained only half of the variation observed. CONCLUSIONS: Although they belong to different genetic groups and have different height and photoperiod sensitivity, the three varieties studied exhibited similar response patterns of development rates among phenological phases and seasons, with the local landrace showing the greatest variation due to its longer vegetative phase and longer stem internodes. The possible adaptive advantages in African savannah environments of bilinear development rates and the associated limitation in height increase are discussed.

Pitfall in pediatric dialysis: malposition of a dialysis catheter mimicking azygos continuation syndrome.

Central venous catheters are established as vascular access in hemodialysis therapy. Vascular catheter misdirection may occur and is a well known problem. We present a rare catheter malposition in a young dialysis patient with consequent dilatation of the azygos vein system, simulating the appearance of an azygos continuation syndrome.

The pattern of genetic diversity of Guinea-race Sorghum bicolor (L.) Moench landraces as revealed with SSR markers.

The Guinea-race of sorghum [Sorghum bicolor (L.) Moench] is a predominantly inbreeding, diploid cereal crop. It originated from West Africa and appears to have spread throughout Africa and South Asia, where it is now the dominant sorghum race, via ancient trade routes. To elucidate the genetic diversity and differentiation among Guinea-race sorghum landraces, we selected 100 accessions from the ICRISAT sorghum Guinea-race Core Collection and genotyped these using 21 simple sequence repeat (SSR) markers. The 21 SSR markers revealed a total of 123 alleles with an average Dice similarity coefficient of 0.37 across 4,950 pairs of accessions, with nearly 50% of the alleles being rare among the accessions analysed. Stratification of the accessions into 11 countries and five eco-regional groups confirmed earlier reports on the spread of Guinea-race sorghum across Africa and South Asia: most of the variation was found among the accessions from semi-arid and Sahelian Africa and the least among accessions from South Asia. In addition, accessions from South Asia most closely resembled those from southern and eastern Africa, supporting earlier suggestions that sorghum germplasm might have reached South Asia via ancient trade routes along the Arabian Sea coasts of eastern Africa, Arabia and South Asia. Stratification of the accessions according to their Snowden classification indicated clear genetic variation between margeritiferum, conspicuum and Roxburghii accessions, whereas the gambicum and guineënse accessions were genetically similar. The implications of these findings for sorghum Guinea-race plant breeding activities are discussed.