Evaluating the stoichiometric trait distributions of cultured bacterial populations and uncultured microbial communities

We measured the stoichiometric trait distribution of cultured freshwater bacterial populations under different resource conditions and compared them to natural microbial communities sampled from three lakes. Trait distributions showed population differences among growth phases and community differences among lakes that would have been masked by only reporting the mean biomass value. The stoichiometric trait distribution of the environmental isolates changed with P availability, growth phase and genotype, with P availability having the strongest effect. The distribution of biomass ratios within each isolate growth experiment were the most constrained during the stages of rapid growth and commonly had unimodal distributions. In contrast to the population distributions, the distribution of N:P and C:P for a similar number of cells from each of the lake communities had narrower stoichiometric distributions and more commonly exhibited multiple modes. © 2019 Society for Applied Microbiology and John Wiley & Sons Ltd     

Traumatisme du testicule chez l’enfant

Introduction

The testicular trauma is uncommon in children and the literature about this topic is very poor. The aim was to investigate the testicular trauma in children from a retrospective study.

Materials and methods

All the French pediatric surgical departments were requested to send their cases of testicular trauma reported between 2000 and 2009. The analysis was performed from the data and the operative report. Isolated scrotal wounds, testicular torsions revealed by trauma, and incomplete files were excluded.

Results

Fifteen departments sent their data and 2 had no cases. From 60 cases, 15 were excluded and 45 selected. The mean age was 12.3 years (2 days–18 years). The circumstances of the trauma were 23 knocks (foot, knee, and fist), 13 falls, 4 motorcycle accidents, 4 unknown traumas, and 1 obstetrical trauma. There were 4 wounds and 41 without wound. A color Doppler sonography was performed in 34 cases (75.5%) with an accurate diagnosis in 30 cases; 2 testicular fractures and 1 intratesticular hematoma were not confirmed at surgery, and 1 epididymal hematoma was not seen on sonography. The lesions were testicular fractures (15), intratesticular hematomas (8), benign testicular blunt traumas (6), spermatic cord hematomas (6), epididymal hematomas (6), isolated hematoceles (3), and avulsion (1). Surgical treatment was done in 33 children and 12 had nonoperative treatment. Among the 15 testicular fractures, 13 were operated (8 sutures and 5 partial orchidectomies) and 2 were only observed. For the intratesticular hematomas, a surgical treatment was performed in 5 children and a nonoperative treatment in 3, with a good evolution. Only 20 children were controlled beyond 4 months, especially the testicular fractures and no secondary testicular atrophy was seen.

Conclusion

The testicular trauma in children is rare and the prognosis is rather good. The color Doppler sonography now allows a good diagnosis in most cases and the surgery can be often avoided in benign blunt trauma. In this situation, it is important to repeat sonography 24 or 48 hours after trauma to ensure there is no fracture or other lesion necessitating a surgical treatment.     

Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo

Previous studies have suggested that α-glucosidase inhibitors such as castanospermine and deoxynojirimycin inhibit dengue virus type 1 infection by disrupting the folding of the structural proteins prM and E, a step crucial to viral secretion. We extend these studies by evaluating the inhibitory activity of castanospermine against a panel of clinically important flaviviruses including all four serotypes of dengue virus, yellow fever virus, and West Nile virus. Using in vitro assays we demonstrated that infections by all serotypes of dengue virus were inhibited by castanospermine. In contrast, yellow fever virus and West Nile virus were partially and almost completely resistant to the effects of the drug, respectively. Castanospermine inhibited dengue virus infection at the level of secretion and infectivity of viral particles. Importantly, castanospermine prevented mortality in a mouse model of dengue virus infection, with doses of 10, 50, and 250 mg/kg of body weight per day being highly effective at promoting survival (P ≤ 0.0001). Correspondingly, castanospermine had no adverse or protective effect on West Nile virus mortality in an analogous mouse model. Overall, our data suggest that castanospermine has a strong antiviral effect on dengue virus infection and warrants further development as a possible treatment in humans.     

Identification of novel small-molecule inhibitors of West Nile virus infection

West Nile virus (WNV) has spread throughout the United States and Canada and now annually causes a clinical spectrum of human disease ranging from a self-limiting acute febrile illness to acute flaccid paralysis and lethal encephalitis. No therapy or vaccine is currently approved for use in humans. Using high-throughput screening assays that included a luciferase expressing WNV subgenomic replicon and an NS1 capture enzyme-linked immunosorbent assay, we evaluated a chemical library of over 80,000 compounds for their capacity to inhibit WNV replication. We identified 10 compounds with strong inhibitory activity against genetically diverse WNV and Kunjin virus isolates. Many of the inhibitory compounds belonged to a chemical family of secondary sulfonamides and have not been described previously to inhibit WNV or other related or unrelated viruses. Several of these compounds inhibited WNV infection in the submicromolar range, had selectivity indices of greater than 10, and inhibited replication of other flaviviruses, including dengue and yellow fever viruses. One of the most promising compounds, AP30451, specifically blocked translation of a yellow fever virus replicon but not a Sindbis virus replicon or an internal ribosome entry site containing mRNA. Overall, these compounds comprise a novel class of promising inhibitors for therapy against WNV and other flavivirus infections in humans.     

Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 2

Novel P2X₇ antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X₇ receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure–activity relationship (SAR) development and results of pain models are presented.