Fixed-dose combination therapy for type 2 diabetes: sitagliptin plus pioglitazone

Importance of the field: Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione pioglitazone into a fixed-dose single-tablet combination. The former component acts mainly to increase prandial insulin secretion; the latter improves insulin sensitivity.

Prior colonisation with Candida species fails to guide empirical therapy for candidaemia in critically ill adults

Objectives Pre-emptive fluconazole (fcz) anti-fungal therapy is often based upon Candida colonisation of at least 2 non-contiguous non-sterile sites. The aim of this study was to evaluate the relationship between candidaemia and prior colonisation of non-sterile sites. Methods A retrospective observational study was performed in the intensive care unit/high dependency unit (ICU/HDU) of a University hospital on alternate years from 1999–2007, where a pre-emptive anti-fungal therapy policy was introduced in 2005. Results A higher proportion of blood isolates were Candida glabrata compared with non-sterile isolates (16/46 vs 106/1062; p

Direct versus delayed pathways in strong-field non-sequential double ionization

We report full-dimensionality quantum and classical calculations of double ionization (DI) of laser-driven helium at 390 nm. Good agreement is observed. We identify the relative importance of the two main non-sequential DI pathways, the direct|with an almost simultaneous ejection of both electrons|and the delayed. We find that the delayed pathway prevails at small intensities independently of total electron energy but at high intensities the direct pathway predominates up to a certain upper-limit in total energy which increases with intensity. An explanation for this increase with intensity is provided.

Systemic Family Therapy for Families who have Experienced Trauma: A Randomised Controlled Trial

This paper describes a randomised controlled trial (RCT) investigation of the added value of systemic family therapy (SFT) over individually focused cognitive behavioural therapy (CBT) for families in which one or more members has suffered trauma and been referred to a community-based psychotherapy centre. The results illustrate how an apparently robust design can be confounded by high attrition rates, low average number of therapeutic sessions and poor protocol adherence. The paper highlights a number of general and specific lessons regarding the resources and processes involved that can act as a model for those planning to undertake studies of this type and scope. A key message is that the challenges of conducting RCTs in ‘real world’ settings should not be underestimated. The wider implications in relation to the place of RCTs within the creation of the evidence base for complex psycho-social interventions is discussed and the current movement towards a phased mixed-methods approach, including the appropriate use of RCTs, which some might argue is a return to the original vision of evidence-based practice (EBP), is affirmed.

Evaluation of a multi-functional nanocarrier for targeted breast cancer iNOS gene therapy.

The present study determines whether the novel designer biomimetic vector (DBV) can condense anddeliver the cytotoxic iNOS gene to breast cancer cells to achieve a therapeutic effect. We have previouslyshown the benefits of iNOS for cancer gene therapy but the stumbling block to future development hasbeen the delivery system.The DBV was expressed, purified and complexed with the iNOS gene. The particle size and chargewere determined via dynamic light scattering techniques. The toxicity of the DBV/iNOS nanoparticleswas quantified using the cell toxicity and clonogenic assays. Over expression of iNOS was confirmed viaWestern blotting and Griess test.The DBV delivery system fully condensed the iNOS gene with nanoparticles less than 100 nm. Transfectionwith the DBV/iNOS nanoparticles resulted in a maximum of 62% cell killing and less than 20%clonogenicity. INOS overexpression was confirmed and total nitrite levels were in the range of 18M.We report for the first time that the DBV can successfully deliver iNOS and achieve a therapeuticeffect. There is significant cytotoxicity coupled with evidence of a bystander effect. We concludethat the success of the DBV fusion protein in the delivery of iNOS in vitro is worthy of future in vivo experiments.