Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons.

Xenotransplantation using porcine donors is rapidly approaching clinical applicability as an alternative therapy for treatment of many end-stage diseases including type 1 diabetes. Porcine neonatal islet cell clusters (NICC) have normalised blood sugar levels for relatively short periods in the preclinical diabetic rhesus model but have met with limited success in the stringent baboon model. Here we report that NICC from genetically modified (GM) pigs deleted for αGal and expressing the human complement regulators CD55 and CD59 can cure diabetes long-term in immunosuppressed baboons, with maximum graft survival exceeding 22 months. Five diabetic baboons were transplanted intraportally with 9,673 - 56,913 islet equivalents (IEQ) per kg recipient weight. Immunosuppression consisted of T cell depletion with an anti-CD2 mAb, tacrolimus for the first 4 months, and maintenance with belatacept and anti-CD154; no anti-inflammatory treatment or cytomegalovirus (CMV) prophylaxis/treatment was given. This protocol was well tolerated, with all recipients maintaining or gaining weight. Recipients became insulin-independent at a mean of 87 ± 43 days post-transplant and remained insulin-independent for 397 ± 174 days. Maximum graft survival was 675 days. Liver biopsies showed functional islets staining for all islet endocrine components, with no evidence of the inflammatory blood-mediated inflammatory reaction (IBMIR) and minimal leukocytic infiltration. The costimulation blockade-based immunosuppressive protocol prevented an anti-pig antibody response in all recipients. In conclusion, we demonstrate that genetic modification of the donor pig enables attenuation of early islet xenograft injury, and in conjunction with judicious immunosuppression provides excellent long-term function and graft survival in the diabetic baboon model.

Arylation Using Sulfonamides: Phenylacetamide Synthesis through Tandem Acylation-Smiles Rearrangement.

A range of electron-poor and heterocyclic sulfonamides react with phenylacetyl chlorides to produce benzhydryl derivatives in a single step. The reaction proceeds via tandem amide bond formation/Dohmori-Smiles rearrangement under the simple conditions of an aqueous base. In the case of o-nosylamides, a further reaction takes place at the nitro group to yield indazoles.

Ruthenium-Catalyzed meta-Carboxylation.

The meta-carboxylation of arenes containing pyridine and other azine-directing groups is reported. Using carbon tetrabromide as the C1 source, ruthenium(III) trichloride catalysis enables functionalization of the arene meta-C-H position, affording carboxy methyl ester products after in situ reaction with methanol.

Clinical nurse specialists: essential resource for an effective NHS.

Despite emerging evidence for the clinical and financial efficacy of the clinical nurse specialist (CNS), the provision of this role is patchy across the country. There is also a risk that incumbent CNS' may be redirected to less specialist work in trusts that do not appreciate the full value of the service that these nurses provide. Optimal and equitable patient access to CNS care will require the development of a strong evidence base showing that specialist nurses not only deliver patient-focused care, but that they can also help to meet healthcare managers' objectives of streamlined, cost-effective clinical services.

An evaluation of a brief motivational intervention among young ecstasy and cocaine users: no effect on substance and alcohol use outcomes.

AIMS: To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young, regular users of MDMA ('ecstasy'), cocaine powder and crack cocaine. DESIGN AND MEASUREMENTS: A randomized trial of the intervention versus a control group who received written health risk information materials only. All participants completed a baseline self-assessment questionnaire before randomization. Outcome measures were self-reported period prevalence abstinence from ecstasy, cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days, recorded at 6-month follow-up via self-completion questionnaire and personal interview. PARTICIPANTS AND SETTING: A total of 342 adolescent and young adult stimulant users (aged 16-22 years) were recruited and 87% were followed-up. The intervention was delivered by a team of 12 agency youth drug workers and two researchers at five locations in Greater London and south-east England. FINDINGS: There were no significant differences in abstinence for ecstasy, cocaine powder or crack cocaine use between the experimental and control groups. Contrasting follow-up with baseline self-reports, there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use. Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants. CONCLUSIONS: Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone. We hypothesize that research recruitment, baseline self-assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use.

Use of libraries and electronic information resources by primary care staff: outcomes from a survey.

OBJECTIVES: To assess the use of existing libraries; usage of the Internet and biomedical databases; and need for training on use of the Internet and biomedical databases for primary care staff. METHODS: A postal survey of general practitioners (GPs), practice nurses (PNs) and practice managers (PMs) in Nottingham and Rotherham, UK. RESULTS: Overall, 243 questionnaires were used. The response rate in Nottingham was 24%, in Rotherham it was 34%. Reported use of libraries was low (30%), with PNs reporting significantly higher usage (65%) than others (P < 0.01). Most respondents reported using the Internet (81%), but fewer (44%) reported using databases. GPs and PNs were significantly more likely to report using databases than PMs (P < 0.01). Lack of training was the most reported barrier to using the Internet (67%) and databases (52%). Overall, 52% of respondents reported wanting Internet training, 64% wanted database training. The percentages requesting training on databases were high among GPs and PNs, but significantly lower for PMs (P = 0.02). CONCLUSIONS: There are differences in the usage of libraries and electronic resources among the primary care team, and in reported training needs. While the reported levels of usage of the Internet and biomedical databases are encouraging, our study identified a training need. If met, this could increase usage further.