Functional developmental similarities and differences in the neural correlates of verbal and nonverbal working memory tasks

Relatively little is known about the functional development of verbal and nonverbal working memory during adolescence. Behavioral studies have demonstrated that WM capacity increases with age, yet relatively few studies have assessed the relationship between brain-activity and age-related changes in WM capacity, especially as it differs across multiple domains. The present study used an n-back task and functional magnetic resonance imaging to assess age-related differences in the neural correlates of word and face working memory tasks. Seventy-eight individuals between the ages of 14 and 27 underwent scans while performing word and face "n-back" working memory tasks. We found very little evidence for age-related differences in accuracy and reaction time. We did find similarities and differences between adolescents and adults in the neural correlates of word and face working memory tasks, even in the absence of performance differences. More specifically, we found similar age-related differences in left superior parietal cortex for both word and face stimuli. We also found that age-related differences in a number of other regions (including left inferior frontal lobe, left supramarginal gyrus, left rolandic sulcus, right cerebellum and left fusiform gyrus) differed according to stimulus type. Our results provide further evidence for continued functional development through adolescence and into adulthood.     

Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics

Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy.     

Randomized Trial of Drain Antisepsis After Mastectomy and Immediate Prosthetic Breast Reconstruction

Background

In this 2-site randomized trial, we investigated the effect of antiseptic drain care on bacterial colonization of surgical drains and infection after immediate prosthetic breast reconstruction.

Methods

With IRB approval, we randomized patients undergoing bilateral mastectomy and reconstruction to drain antisepsis (treatment) for one side, with standard drain care (control) for the other. Antisepsis care included both: chlorhexidine disc dressing at drain exit site(s) and irrigation of drain bulbs twice daily with dilute sodium hypochlorite solution. Cultures were obtained from bulb fluid at 1 week and at drain removal, and from the subcutaneous drain tubing at removal. Positive cultures were defined as ≥1+ growth for fluid and >50 CFU for tubing.

Results

Cultures of drain bulb fluid at 1 week (the primary endpoint) were positive in 9.9 % of treatment sides (10 of 101) versus 20.8 % (21 of 101) of control sides (p = 0.02). Drain tubing cultures were positive in 0 treated drains versus 6.2 % (6 of 97) of control drains (p = 0.03). Surgical site infection occurred within 30 days in 0 antisepsis sides versus 3.8 % (4 of 104) of control sides (p = 0.13), and within 1 year in three of 104 (2.9 %) of antisepsis sides versus 6 of 104 (5.8 %) of control sides (p = 0.45). Clinical infection occurred within 1 year in 9.7 % (6 of 62) of colonized sides (tubing or fluid) versus 1.5 % (2 of 136) of noncolonized sides (p = 0.03).

Conclusions

Simple and inexpensive local antiseptic interventions with a chlorhexidine disc and hypochlorite solution reduce bacterial colonization of drains, and reduced drain colonization was associated with fewer infections.     

miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention.