Apnoeic episodes induced by smothering: two cases identified by covert video surveillance.

Recurrent cyanotic episodes associated on some occasions with loss of consciousness due to cerebral hypoxia were investigated by long term tape recordings of breathing activity, oxygen saturation, air flow, electrocardiographic activity, and in some cases electroencephalographic activity. In 51 infants and children the mechanisms for the cyanotic episodes were identified (prolonged expiratory apnoea in 45, sleep related airway obstruction in three, seizure induced apnoea in one, behaviour induced apnoea in one). In one child apnoea was suspected as being caused by suffocation (smothering) by the mother. This was confirmed after enlisting the help of the police, who undertook covert video surveillance during cyanotic episodes. Each cyanotic episode was associated with a pattern of disturbance on the multichannel tape recordings which may be pathognomonic of this type of apnoea. A second infant with cyanotic episodes in whom smothering was suspected was referred for similar investigation after the availability of video recordings became established. Maternal smothering was again supported by specific patterns on multichannel tape recordings and confirmed by video surveillance. Diagnosis by video surveillance produces unequivocal evidence in these cases and avoids the need for medical and nursing staff to confront the mother with a possibly incorrect suspicion or in a court of law.     

Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens

A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.     

Identifying reproductive events using archival tags: egg‐laying behaviour of the small spotted catshark Scyliorhinus canicula

The use of archival depth telemetry as a means of remotely assessing the reproductive rates of free‐ranging fishes is explored. This is achieved by electronically tracking the vertical movements of individual female small spotted catsharks Scyliorhinus canicula in the natural environment, whilst simultaneously evaluating the temporal and vertical distributions of egg‐laying in this species. Distinctive patterns of short‐term (0·3–3·7 h), shallow‐water activity are documented in the time–depth profiles of female S. canicula that occur at an appropriate depth (1·0–2·3 m) and periodicity (every 10–12 days) to represent egg‐laying behaviour. Putative egg‐laying behaviour was exhibited simultaneously by two individually tracked female S. canicula during late‐spring and early‐summer. The results highlight that, provided species behaviour is suitable and complementary methods such as previous data, laboratory experiments and field surveys can be used to validate the patterns observed, archival depth telemetry offers an unobtrusive means by which egg production and egg‐laying behaviour of free‐living fishes can be estimated. As precise information regarding life‐history parameters is difficult to obtain for free‐ranging fish species, this technique could be used to improve the parameterization of species demographic models that are relevant to the management of wild fish populations.     

Inhibitors of the Yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches

The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a diversity of chemotypes and novel pTyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. We demonstrate that the applications of high throughput and virtual screening, when guided by structural binding mode analysis, is an effective approach for identifying potent and selective inhibitors of YopH and other protein phosphatases for rational drug design.     

Identification,design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists

Nonstructural protein 1 (NS1) plays a crucial function in the replication, spread, and pathogenesis of influenza virus by inhibiting the host innate immune response. Here we report the discovery and optimization of novel pyrazolopyridine NS1 antagonists that can potently inhibit influenza A/PR/8/34 replication in MDCK cells, rescue MDCK cells from cytopathic effects of seasonal influenza A strains, reverse NS1-dependent inhibition of IFN-β gene expression, and suppress the slow growth phenotype in NS1-expressing yeast. These pyrazolopyridines will enable researchers to investigate NS1 function during infection and how antagonists can be utilized in the next generation of treatments for influenza infection.