The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

The aim of the present meta-analysis was to assess the safety profile of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors in comparison with placebo as add-on to metformin therapy in patients with type 2 diabetes. Randomized controlled trials and controlled clinical trials were identified by searching Pubmed, Embase and the Cochrane Central Register of Controlled Trials database until 15 July 2013. All included studies were critically appraised and analysed with the use of Review Manager 5.1.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement protocol. Twenty randomized and double-blinded studies published in 22 articles fulfilled the inclusion criteria for meta-analysis. The overall results demonstrated that the use of oral antidiabetic agents (analysed separately and together) was not associated with any significantly increased risk of any serious adverse events including hypoglycaemia and gastrointestinal disorders. Moreover, the use of DPP-4 or SGLT-2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin. However, we found that the SGLT-2 inhibitors were more likely to cause a genital infection. Despite some limitations, the findings of this meta-analysis indicate that DPP-4 or SGLT-2 inhibitors have favourable safety profile, and such therapy, when combined with metformin is well tolerated.

Systematic review of the effectiveness of biological therapy for active moderate to severe ulcerative colitis.

BACKGROUND AND AIM: The aim of this systematic review was to evaluate the efficacy and safety of biological agents (vedolizumab, abatacept, visilizumab, golimumab) in patients with active moderate to severe ulcerative colitis. METHODS: This paper was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The systematic literature search was performed in PubMed, Embase, Cochrane Library, and other databases until December 27, 2013 to identify randomized controlled trials fulfilling the established inclusion criteria for this review. RESULTS: Eight randomized controlled trials were included in the systematic review. Vedolizumab was significantly more effective compared with placebo (P < 0.05) increasing the percentage of patients with a clinical response, clinical remission and mucosal healing in the induction phase, and patients with a clinical remission and mucosal healing in the maintenance phase. Similarly, golimumab was significantly more effective than placebo (P < 0.05) regarding the percentage of patients with a clinical response and mucosal healing in the induction phase, and patients with a clinical response, clinical remission, and mucosal healing in the maintenance phase. The safety of these two biological agents was comparable with placebo during the treatment (P > 0.05). However, the efficacy of visilizumab or abatacept was related to the higher risk of treatment failure and a worse safety profile than placebo. CONCLUSIONS: The results of the systematic review demonstrated that the efficacy and safety of particular biological agents are differentiated. Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.

The effect of age and sexual maturation on thermal preferences of honey bee drones.

The thermal preferences of Apis mellifera carnica drones (male individuals) are poorly understood, though their reproductive quality affects the quality of the inseminated queen and the whole honey bee colony. Therefore, the aim of this study was to determine the thermal preferences of individual drones according to their age and sexual maturity. Drones at the ages of 1, 5, 10, 15, 20 and 25 days were tested. The drones were placed on a platform in a temperature gradient in the range 20 °C and 46 °C. The thermal preferences of the drones were measured with the use of a thermal-imaging camera. Drones significantly differed with their choice of a preferred temperature. The one-day-old and the 25-day-old drones preferred the lowest temperatures. A slightly higher temperature was preferred by the 5-day-old drones, and the highest temperature was chosen by the drones at the ages of 10, 15, and 20 days. The changes in the thermal preferences of drones correspond to physiological changes occurring with age and connected with the rate of sexual maturation.

Effectiveness of targeted therapy in patients with previously untreated metastatic breast cancer: a systematic review and meta-analysis.

Breast cancer is the most common cancer and the most frequent cause of death in women. Targeted therapies offer a possibility of effective and individualized therapy based on the molecular profile of the tumor. The aim of this systematic review was to evaluate the efficacy and safety of targeted agents added to chemotherapy or endocrine therapy in patients with previously untreated metastatic breast cancer (MBC) depending on their human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status (positive or negative). The systematic literature search was performed in PubMed, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs). Thirteen trials were included. The addition of trastuzumab, pertuzumab, bevacizumab, or lapatinib to chemotherapy significantly (P < .05) improved objective response rate (ORR), time to failure (TTF), and overall survival (OS) in patients with HER2-positive (HER2(+)) disease. Trastuzumab or lapatinib combined with endocrine therapy significantly (P < .05) improved ORR, time to progression (TTP), and progression-free survival (PFS) in patients with HER2(+) and HR(+) disease. In patients with HER2-negative (HER2(-)) cancer, bevacizumab or lapatinib added to chemotherapy significantly (P < .05), improved ORR but did not prolong PFS and OS (P > .05). In patients with HER2(-) and HR(-) disease, trastuzumab combined with chemotherapy did not significantly improve (P > .05) ORR or PFS. Targeted therapies also increased the overall risk of adverse events. So far, there is a lack of published results for everolimus and trastuzumab emtansine trials in patients with previously untreated MBC. The addition of targeted therapy to chemotherapy or endocrine therapy using HER2 and HR status significantly improved ORR, PFS, and OS in patients with previously untreated MBC.

Effectiveness of targeted therapy as monotherapy or combined therapy in patients with relapsed or refractory multiple myeloma: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review was to evaluate the efficacy and safety of targeted agents used as monotherapy or combined therapy in patients with relapsed/refractory multiple myeloma (MM). METHODS: The systematic literature search was conducted in PubMed, Embase, Cochrane Library till 27 May 2013. RESULTS: Four randomized controlled trials were included. The meta-analysis showed that combined therapy significantly improved progression-free survival compared with monotherapy (P < 0.05). However, there was not a significant difference between monotherapy and combined therapy in overall survival (P > 0.05). The combined therapy also significantly increased the risk of serious adverse events and grade 3/4 AEs compared to monotherapy (P < 0.05). Overall, the results of comparisons between monotherapy and combined therapy in individual trials were differentiated, and some combinations were not more effective than monotherapy (bortezomib plub bevacizumab vs. bortezomib and thalidomide plus INFα vs. thalidomide) which emphasizes the role of individualized therapy in relapsed/refractory MM especially in the elderly or patients with significant comorbidities. CONCLUSIONS: The results of this meta-analysis showed that combined therapy is superior to monotherapy only in some end points and it is less tolerated in patients with relapsed/refractory MM. Thus, the overall superiority of complex therapy to monotherapy depends on the combination of the targeted agents.

Cooperative behavior of laboratory rats (Rattus norvegicus) in an instrumental task.

Cooperation is a cognitively demanding, complex social behavior, found primarily in primates. Here we investigated mutualism in rats (Rattus Norvegicus), a simple form of cooperation in which two subjects work on operant task, receiving immediate and simultaneous sucrose reward for a joint action. To receive the sucrose reward, familiar pairs of rats were required to nose poke simultaneously. Following 44 training days, we examined the relation of social contact and ultrasonic vocalizations to the rat's cooperative behavior by testing the effects of inserting opaque, wire-mesh, or no partition--between subjects. Cooperative behavior (simultaneous nose-poking): (a) increased gradually during initial training; (b) decreased with the opaque partition (restricting visual, acoustic, and physical communication); (c) increased with a wire mesh partition restricting only physical contact); and (d) increased with the number of 50 kHz USV "happy" calls and the intensity of social interaction. The possibility of studying the development of cooperative behavior in laboratory rats using a simple procedure based on commercially available equipment may prove useful in modeling determinants of social behavior.

A magnetic field effect on learning in male golden hamsters.

The aim of this experiment was to investigate the influence of repeated exposure to 10, 20, 30 or 40 Hz magnetic fields at 0.1T on the learning of male golden hamsters in a Skinner box, in which the animals learned to press a lever to receive a food reward. The latency of the first response was not affected by exposure to the magnetic fields used in this experiment. No significant field-dependent effects on the performance of the task were observed in males exposed to 10 and 20 Hz magnetic fields at 0.1T. However, exposure significantly improved the learning of the task in animals exposed to 30 and 40 Hz magnetic fields at 0.1T.