Storage protein activator controls grain protein accumulation in bread wheat in a nitrogen dependent manner.

The expression of cereal grain storage protein (GSP) genes is controlled by a complex network of transcription factors (TFs). Storage protein activator (SPA) is a major TF acting in this network but its specific function in wheat (Triticum aestivum L.) remains to be determined. Here we generated an RNAi line in which expression of the three SPA homoeologs was reduced. In this line and its null segregant we analyzed GSP accumulation and expression of GSP and regulatory TF genes under two regimes of nitrogen availability. We show that down regulation of SPA decreases grain protein concentration at maturity under low but not high nitrogen supply. Under low nitrogen supply, the decrease in SPA expression also caused a reduction in the total quantity of GSP per grain and in the ratio of GSP to albumin-globulins, without significantly affecting GSP composition. The slight reduction in GSP gene expression measured in the SPA RNAi line under low nitrogen supply did not entirely account for the more significant decrease in GSP accumulation, suggesting that SPA regulates additional levels of GSP synthesis. Our results demonstrate a clear role of SPA in the regulation of grain nitrogen metabolism when nitrogen is a limiting resource.

Complications During Inter-Hospital Transfer of Patients with Acute Ischemic Stroke for Endovascular Therapy.

Purpose: Few data are available on complications occurring during inter-hospital transfer from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (EVT) after large vessel occlusion (LVO). Therefore, we prospectively studied data from consecutive patients transferred from our PSC to the next CSC during 4 years to determine the incidence and risk factors of complications during transfer. Methods: This observational, single-center study included consecutive patients transferred from January 1, 2015 to December 31, 2018. During inter-hospital transfer, all medical incidents were systematically recorded. A new complete clinical examination was performed on arrival at the CSC. Results: Among the 253 patients transferred to the CSC during the study period, 68 (26.9%) had one or more complications. In 11 patients (4.3%) these were life-threatening and required emergency intervention by a physician. Baseline characteristics were not different between patients with and without complications, except for the LVO location. Specifically, basilar artery (BA) occlusion was strongly associated with complications during the transport (p < 0.0005). Conclusion: Complications occurred in 26.9% of patients during transfer. Only BA occlusion could predict complication during transfer. Future studies should identify variables to help stratifying patients at high and low risk of complications during transportation.

Which Patients Require Physician-Led Inter-Hospital Transport in View of Endovascular Therapy?

INTRODUCTION: The current guidelines advocate the implementation of stroke networks to organize endovascular treatment (ET) for patients with acute ischemic stroke due to large vessel occlusion (LVO) after transfer from a Primary Stroke Centre (PSC) to a Comprehensive Stroke Centre (CSC). In France and in many other countries around the world, these transfers are carried out by a physician-led mobile medical team. However, with the recent broadening of ET indications, their availability is becoming more and more critical. Here, we retrospectively analysed data of patients transferred from a PSC to a CSC for potential ET to identify predictive factors of major complications (MC) at departure and during transport that absolutely require the presence of a physician during interhospital transfer. METHODS: This observational, single-centre study included patients with evidence of intracranial LVO transferred for ET from Perpignan to a 156 km-distant CSC between January 1, 2015 and -December 31, 2018. We compared 2 groups: MC group (patients who required emergency intervention by the medical team due to life-threatening complications, including need of mechanical ventilation at departure) and non-MC group (all other patients who experienced no or only minor complications that could be managed by the emergency paramedics alone). RESULTS: Among the 253 patients who were transferred to the CSC, 185 (73.1%) had no complication, 57 (22.6%) minor complications, and 11 (4.3%) had MC. In multivariate analysis, MC was associated with basilar artery (BA) occlusion (p < 0.0001), initial National Institute of Health Stroke Scale (NIHSS) score >22 (p < 0.005), and history of atrial fibrillation (p < 0.04). Among the 168 patients treated with intravenous thrombolysis (IVT), only 1 patient (0.6%) had MC due to an IVT-related adverse event during transfer. CONCLUSIONS: Physician-led inter-hospital transports are warranted for patients with BA occlusion, initial NIHSS score >22, or history of atrial fibrillation. For the other patients, transfer without a physician may be considered, even if treated with IVT.

Transcriptional and metabolic alternations rebalance wheat grain storage protein accumulation under variable nitrogen and sulfur supply.

Wheat (Triticum aestivum L.) grain storage proteins (GSPs) are major determinants of flour end-use value. Biological and molecular mechanisms underlying the developmental and nutritional determination of GSP accumulation in cereals are as yet poorly understood. Here we timed the accumulation of GSPs during wheat grain maturation relative to changes in metabolite and transcript pools in different conditions of nitrogen (N) and sulfur (S) availability. We found that the N/S supply ratio modulated the duration of accumulation of S-rich GSPs and the rate of accumulation of S-poor GSPs. These changes are likely to be the result of distinct relationships between N and S allocation, depending on the S content of the GSP. Most developmental and nutritional modifications in GSP synthesis correlated with the abundance of structural gene transcripts. Changes in the expression of transport and metabolism genes altered the concentrations of several free amino acids under variable conditions of N and S supply, and these amino acids seem to be essential in determining GSP expression. The comprehensive data set generated and analyzed here provides insights that will be useful in adapting fertilizer use to variable N and S supply, or for breeding new cultivars with balanced and robust GSP composition.

Cutaneous leishmaniasis: treatment with low-dose oral fluconazole with an excellent cosmetic result.

We report the successful treatment of cutaneous leishmaniasis in a 6-year-old girl who presented with a solitary lesion on the cheek. A low dose of 3 mg/kg/day of fluconazole was used, with remarkable improvement at 6 weeks and complete regression at 12 weeks, excellent cosmetic results, and no relapse during a follow-up of 1 year.

Reconstruction of the median anterior skull base with an intracranial free radial forearm flap after recurrent resection of tumour.

We report a case of a median anterior skull base defect that was reconstructed with a free radial forearm flap. The flap was used intracranially, whereas the vascular anastomosis was made extracranially, with the pedicle running through a burr hole in the skull. This technique was succesful in sealing the skull base from the nasal cavity and preventing leakage of cerebrospinal fluid, infection, or herniation of brain tissue. We report the reconstructive procedure, an overview of other options, and the reasons for the decisions in this case.

Straylight before and after LASEK in myopia: changes in retinal straylight.

PURPOSE: To quantify the changes in retinal straylight that occur after laser-assisted subepithelial keratectomy (LASEK). METHODS: This prospective study included 86 eyes of 49 patients who were scheduled for LASEK surgery. Patients were divided into groups based on their preoperative contact lens wear habits: rigid lenses (RCL), soft lenses (SCL), spectacles after a period of contact lenses (SaC), and spectacles only (Specs). Retinal straylight was tested before surgery and 6 months after surgery with the compensation comparison method. Straylight was also compared to a normal reference database. The difference with the average straylight increase with age, called base- and age-corrected (BAC) straylight, was also studied. RESULTS: Before surgery, BAC straylight was found to be strongly elevated, with a value of 0.15 +/- 0.14 log units. After LASEK, this decreased to 0.00 +/- 0.14 log units. The reduction was significant (paired t-test, P << 0.01) and correlated with preoperative BAC straylight levels (r(2) = 0.332; P << 0.01). There was no correlation between the straylight change and the spherical equivalent of the laser refractive correction (r(2) = 0.042; P = 0.059). Preoperative wear of soft contact lenses increased the BAC straylight by approximately 0.06 log units, with respect to the spectacles groups (P < 0.05, unpaired t-test), but after surgery, this difference was no longer found (P > 0.05). CONCLUSIONS: Higher than normal preoperative BAC straylight was found to normalize after LASEK refractive surgery. Wearing soft contact lenses causes an additional increase in preoperative BAC straylight that is eliminated after LASEK.

Nucleotide polymorphism in the wheat transcriptional activator Spa influences its pattern of expression and has pleiotropic effects on grain protein composition, dough viscoelasticity, and grain hardness.

Storage protein activator (SPA) is a key regulator of the transcription of wheat (Triticum aestivum) grain storage protein genes and belongs to the Opaque2 transcription factor subfamily. We analyzed the sequence polymorphism of the three homoeologous Spa genes in hexaploid wheat. The level of polymorphism in these genes was high particularly in the promoter. The deduced protein sequences of each homoeolog and haplotype show greater than 93% identity. Two major haplotypes were studied for each Spa gene. The three Spa homoeologs have similar patterns of expression during grain development, with a peak in expression around 300 degree days after anthesis. On average, Spa-B is 10 and seven times more strongly expressed than Spa-A and Spa-D, respectively. The haplotypes are associated with significant quantitative differences in Spa expression, especially for Spa-A and Spa-D. Significant differences were found in the quantity of total grain nitrogen allocated to the gliadin protein fractions for the Spa-A haplotypes, whereas the synthesis of glutenins is not modified. Genetic association analysis between Spa and dough viscoelasticity revealed that Spa polymorphisms are associated with dough tenacity, extensibility, and strength. Except for Spa-A, these associations can be explained by differences in grain hardness. No association was found between Spa markers and the average single grain dry mass or grain protein concentration. These results demonstrate that in planta Spa is involved in the regulation of grain storage protein synthesis. The associations between Spa and dough viscoelasticity and grain hardness strongly suggest that Spa has complex pleiotropic functions during grain development.