Preparation and Supramolecular Recognition of Multivalent Peptide-Polysaccharide Conjugates by Cucurbit[8]uril in Hydrogel Formation.

Supramolecular hydrogels were fabricated by physically cross-linking phenylalanine functionalized polysaccharides with cucurbit[8]uril in water. We report a facile 2-step method of functionalization of the polysaccharides hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), and guar with the dipeptide Phe-Cys. Addition of cucurbit[8]uril to the functional polysaccharides initiated physical cross-linking on account of strong 1:2 "homoternary" complexes with the pendant Phe residues. In particular, HA and CMC based soft hydrogels displayed impressive viscoelastic behavior which was characterized using rheology, demonstrating accessibility to an array of material properties which would find broad applicability in many fields.M.J.R. thanks the University of Cambridge Chemical Biology and Molecular Medicine PhD Training Programme for funding. OAS thanks ERC Starting Investigator Grant (ASPiRe). The authors would also like to thank Silvia Sonzini for her assistance with collecting ITC data.This is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/acs.biomac.5b0068

Evaluation of the Long-Lasting Insecticidal Net Interceptor LN: Laboratory and Experimental Hut Studies against Anopheline and Culicine Mosquitoes in Northeastern Tanzania

Long lasting insecticidal nets (LN) are a primary method of malaria prevention. Before new types of LN are approved they need to meet quality and efficacy standards set by the WHO Pesticide Evaluation Scheme. The process of evaluation has three phases. In Phase I the candidate LN must meet threshold bioassay criteria after 20 standardized washes. In Phase II washed and unwashed LNs are evaluated in experimental huts against wild, free flying anopheline mosquitoes. In Phase III the LN are distributed to households in malaria endemic areas, sampled over three years of use and tested for continuing insecticidal efficacy. Interceptor® LN (BASF Corporation, Germany) is made of polyester netting coated with a wash resistant formulation of alpha-cypermethrin. Interceptor LN was subjected to bioassay evaluation and then to experimental hut trial against pyrethroid-susceptible Anopheles gambiae and An. funestus and resistant Culex quinquefasciatus. Mosquito mortality, blood feeding inhibition and personal protection were compared between untreated nets, conventional alpha-cypermethrin treated nets (CTN) washed 20 times and LNs washed 0, 20 and 30 times. In Phase I Interceptor LN demonstrated superior wash resistance and efficacy to the CTN. In the Phase II hut trial the LN killed 92% of female An. gambiae when unwashed and 76% when washed 20 times; the CTN washed 20 times killed 44%. The LN out-performed the CTN in personal protection and blood-feeding inhibition. The trend for An. funestus was similar to An. gambiae for all outcomes. Few pyrethroid-resistant Cx. quinquefasciatus were killed and yet the level of personal protection (75-90%) against Culex was similar to that of susceptible An. gambiae (76-80%) even after 20 washes. This protection is relevant because Cx. quinquefasciatus is a vector of lymphatic filariasis in East Africa. After 20 washes and 60 nights’ use the LN retained 27% of its initial insecticide dose. Interceptor LN meets the approval criteria set by WHO and is recommended for use in disease control against East African vectors of malaria and filariasis. Some constraints associated with the phase II evaluation criteria, in particular the washing procedure, are critically reviewed

Interceptor® long-lasting insecticidal net: phase III evaluation over three years of household use and calibration with Phase II experimental hut outcomes.

BACKGROUND: Long-lasting insecticidal nets (LN) are an effective tool for malaria prevention. The World Health Organization Pesticide Evaluation Scheme has established evaluation criteria to facilitate registration for public use. A household randomised trial was conducted in Tanzania according to WHOPES Phase III procedures to evaluate the alpha-cypermethrin coated Interceptor® LN (BASF) over three years' use. Outcomes were calibrated against results of Phase II experimental hut trials. METHODS: Interceptor LN (200 mg/m(2) alpha-cypermethrin) and conventionally treated nets CTN (40 mg/m(2) alpha-cypermethrin) were randomly distributed to 934 households. At 6-monthly intervals, household surveys recorded net use, durability, adverse effects, user acceptance and washing practices. Concurrently, 30 nets of each type were collected and tested for knock-down and kill of Anopheles gambiae mosquitoes in cone and tunnel bioassays. Alpha-cypermethrin content of nets was assessed annually. RESULTS: At 12 months 97% of Interceptor LN met the efficacy criteria by cone or tunnel test; this pass rate declined to 90% at 24 months and 87% at 36 months. In contrast only 63% of CTN met the efficacy criteria at 12 months, 14 % at 24 months and 0% at 36 months. The alpha-cypermethrin content at 36 months on Interceptor LN was 20% (42 ± 13 mg/m(2)) of the initial content but on CTNs only 4% (1.3 ± 1.6 mg/m(2)) remained. Interceptor LN was reported to be used year-round and washed 4.3 times/year. A few recalled facial tingling during the first days of use but this did not deter usage. The average number of holes at 36 months was 18, hole area per net was 229 cm(2) and hole index was 332. Insecticide content and cone bioefficacy of LN and CTN after 36 months' use were similar to that of LN and CTN used in earlier Phase II hut trials, but while the 20 times washed LN tested in experimental huts gave adequate personal protection the 20 times washed CTN did not. CONCLUSIONS: More than 80% Interceptor LN fulfilled the WHOPES Phase III criteria at 36 months and thus the LLIN was granted full WHO recommendation. Phase III outcomes at 36 months were anticipated by Phase II outcomes after 20 standardized washes

Open urethroplasty versus endoscopic urethrotomy - clarifying the management of men with recurrent urethral stricture (the OPEN trial) : study protocol for a randomised controlled trial

Peer reviewedPublisher PD

Phase III evaluation of the insecticidal efficacy and durability of a deltamethrin-treated polypropylene long-lasting net LifeNet®, in comparison with long-lasting nets made from polyester and polyethylene: study protocol.

BACKGROUND: Universal coverage of long-lasting insecticidal nets (LNs) made from polyester or polyethylene fibres has been adopted as the standard of care to control malaria among at-risk populations. To obtain a WHO recommendation, LNs must undergo prospective monitoring of insecticidal efficacy against mosquito vectors over 3 years of household use. The retention of bioefficacy and physical durability of a LN is influenced by net usage practices, textile polymer material and insecticide treatment technology. Fabric durability is the critical factor which determines the interval required between LN replacement campaigns. To investigate factors known to affect LN durability and bioefficacy, we describe a three-arm WHO Pesticide Evaluation Scheme (WHOPES) Phase III evaluation of a LN made uniquely from polypropylene (LifeNet®, Bayer CropScience) compared to standard LNs made from polyester and polyethylene, all treated with deltamethrin, over 3 years of use. METHODS: This is a prospective three-arm household randomized, equivalence trial of LNs in Tanzania, with nets as the unit of observation. Equal numbers of houses will be randomized to receive deltamethrin-treated polypropylene, polyester or polyethylene LNs; all sleeping spaces in a given household will be provided with one type of net. Bioefficacy (insecticidal activity against mosquitoes), insecticide content of net fibres, and fabric integrity (number, location and size of holes) will be measured every 6 months, using WHO cone or tunnel bioassays, chemical analysis and calculation of hole index, respectively. A cohort of LNs will be surveyed annually to assess survivorship (median LN survival time) and cumulative loss of fabric integrity. Field durability outcomes will be compared with laboratory strength tests. DISCUSSION: This is the first trial to compare the relative durability of three LNs each made from a different textile polymer, treated with the same insecticide, in the same community side-by-side over 3 years of use. Trial findings will 1) guide global health organizations on procurement policy and the type of textile polymer which maximizes the interval between LN replacement campaigns, and 2) stimulate manufacturers to improve product performance and development of longer lasting polymers. A full WHO recommendation may be granted to LifeNet® upon successful Phase III completion

Temperatures achieved in human and canine neocortex during intraoperative passive or active focal cooling

Focal cortical cooling inhibits seizures and prevents acquired epileptogenesis in rodents. To investigate the potential clinical utility of this treatment modality, we examined the thermal characteristics of canine and human brain undergoing active and passive surface cooling in intraoperative settings. Four patients with intractable epilepsy were treated in a standard manner. Before the resection of a neocortical epileptogenic focus, multiple intraoperative studies of active (custom-made cooled irrigation-perfused grid) and passive (stainless steel probe) cooling were performed. We also actively cooled the neocortices of two dogs with perfused grids implanted for 2 hours. Focal surface cooling of the human brain causes predictable depth-dependent cooling of the underlying brain tissue. Cooling of 0.6–2°C was achieved both actively and passively to a depth of 10–15 mm from the cortical surface. The perfused grid permitted comparable and persistent cooling of canine neocortex when the craniotomy was closed. Thus, the human cortex can easily be cooled with the use of simple devices such as a cooling grid or a small passive probe. These techniques provide pilot data for the design of a permanently implantable device to control intractable epilepsy