The possible implications of our findings are considerable. Residents of homes are typically frail and many have a propensity to falls. In designing safer environments for older people, the type of floor should be chosen to minimise the risk of fracture. This may result in a major reduction in fractures in the elderly.

Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving >25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion-templated freeze-drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non-nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z-average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four-fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible.

Background: Data from studies with undergraduate and postgraduate taught students suggest that they are at an increased risk of having mental health problems, compared to the general population. By contrast, the literature on doctoral researchers (DRs) is far more disparate and unclear. There is a need to bring together current findings and identify what questions still need to be answered. Methods: We conducted a mixed methods systematic review to summarise the research on doctoral researchers' (DRs) mental health. Our search revealed 52 articles that were included in this review. Results: The results of our meta-analysis found that DRs reported significantly higher stress levels compared with population norm data. Using meta-analyses and meta-synthesis techniques, we found the risk factors with the strongest evidence base were isolation and identifying as female. Social support, viewing the PhD as a process, a positive student-supervisor relationship and engaging in self-care were the most well-established protective factors. Conclusions: We have identified a critical need for researchers to better coordinate data collection to aid future reviews and allow for clinically meaningful conclusions to be drawn. Systematic review registration: PROSPERO registration CRD42018092867

No abstract

Four female members of the same family suffering from a rare combination of oesophageal leiomyomatosis and an Alport-like nephropathy are described. The disease is characterized by marked thickening of the oesophageal wall, usually also involving the proximal stomach, with or without discernible leiomyomatous nodule formation. All cases were treated surgically by oesophagectomy with symptomatic relief, and there was no evidence of recurrence on follow-up (2-37 years). The syndrome appears to be dominantly inherited, affects children and young adults, and may also be associated with leiomyomatosis of other viscera. Previously reported cases and possible aetiologies are reviewed, and evidence that this association represents a new variant of Alport's syndrome is discussed.

The effect of mannitol (1.0 gm/kg) and furosemide (0.7 mg/kg), alone and in combination, on the blood-brain extracellular fluid and cerebrospinal fluid (CSF) osmotic gradient, elevated intracranial pressure (ICP), CSF and serum osmolality, and urine output was studied in 26 mongrel dogs. Mannitol and furosemide, when used together, produced a greater (62.4% versus 56.6%) and more sustained (5 hours versus 2 hours) fall in ICP than mannitol alone. This correlated with a prolongation of the reversal of the blood-brain osmotic gradient (-3.4 to + 38.5 mOsm/kg) and a rate of urine formation 15 times control values. There was a transient but not significant fall in serum Na+ with the combined treatment, but the arterial pressure did not vary from pretreatment levels. The results from this present study suggest that the distal loop diuretics in a dose of less than 1.0 mg/kg act synergistically with mannitol by causing preferential excretion of water over solute in the renal distal tubule, and thereby sustaining the osmotic gradient initially established by the mannitol infusion. It is possible, but unlikely in the doses used, that the additive effect of furosemide on reducing ICP in the presence of mannitol is due to interference with CSF formation or Na+ and H2O movement across the blood-brain barrier.

No abstract

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 x 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.