Controlled release of lipase from Candida rugosa loaded into hydrogels of N-isopropylacrylamide and itaconic acid

The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37°C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems.     

Incidence and risk factors of early surgical complications in young renal transplant recipients: A persistent challenge

There is a paucity of data on the rate of urological and vascular complications in very young children after kidney transplant. We conducted a study on the incidence and risk factors for early post‐transplant surgical complications in young recipients (<5 years) over three decades. The primary outcome was any urological or vascular complication within 30 days of transplant, and the secondary outcome was incidence rate of graft failure reported as per 1000 person‐years. Risk factors associated with surgical complications were analyzed by logistic regression. There were 22 (26.5%) complications in 21 children with vascular thrombosis being the most common complication. There was no significant difference in the number of complications in period 1 (1985‐1994) and period 2 (1995‐2014) (P=.1). The incidence rate of graft failure was higher in period 1 (IR 70.8, 95% CI 41.1, 121.9) compared to period 2 (IR 20.7, 95% CI 9.3, 46.0). Cumulative incidence of graft survival at 1, 3, and 5 years' post‐transplant was 96.5%, 92.6%, and 90%, respectively, in those without compared to 71%, 65.1%, and 58.6%, respectively, in children with complications. In conclusion, early surgical, especially vascular, complications are quite common in young renal transplant recipients and lead to significantly reduced graft survival.     

Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors

The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatents have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in 29 pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and 30 healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short‐term verbal memory. Hippocampal subfields (Cornus Ammonis (CA) 1, CA2‐3, dentate gyrus (DG)‐CA4, stratum radiatum—lacunosum—moleculare, and subiculum) were segmented using the Multiple Automatically Generated Templates for Different Brains automated segmentation algorithm. Neuropsychological assessment of short‐term verbal associative memory was performed in a subset of brain tumor survivors (N = 11) and typically developing children (N = 16), using the Children's Memory Scale or Wechsler's Memory Scale—third edition. Repeated measures analysis of variance showed that pediatric brain tumor survivors had significantly smaller DG‐CA4, CA1, CA2‐3, and stratum radiatum‐lacunosum‐moleculare volumes compared with typically developing children. Verbal memory performance was positively related to DG‐CA4, CA1, and stratum radiatum‐lacunosum‐moleculare volumes in pediatric brain tumor survivors. Unlike the brain tumor survivors, there were no associations between subfield volumes and memory in typically developing children and adolescents. These data suggest that specific subfields of the hippocampus may be vulnerable to brain cancer treatments, and may contribute to impaired episodic memory following brain cancer treatment in childhood.     

Exposure to environmental tobacco smoke in the workplace in Macedonia: where are we now?

To assess the prevalence and the level of exposure to environmental tobacco smoke (ETS) in the workplace after the enactment of the law restricting indoor smoking in Macedonia, we performed a cross-sectional, self-administered questionnaire study including 372 never-smoking workers recruited from six workplaces. We found a high prevalence of workers exposed to ETS in the workplace (27.4 %) with no significant difference between particular occupation groups. We found no significant difference in the prevalence of passive smokers in the workplace between this study and our study conducted before the law was enacted (31.5 % vs. 27.4 %, P=0.324). The prevalence of workers exposed to ETS for less than three hours a day was significantly lower than of passive smokers with longer exposure (28.4 % vs. 71.6 %, P=0.038). The prevalence of workers exposed to ETS from less than 10 cigarettes smoked by coworkers per day was lower than the prevalence of workers with higher exposure, but statistical significance was not reached (37.9 % vs. 62.1 %, P=0.087). Our findings indicate a high prevalence and a high level of exposure to ETS in the workplace, which calls for stricter adherence to smoking-free legislation or even the total ban of smoking in the workplace.     

Virus-like particle-induced protection against MRSA pneumonia is dependent on IL-13 and enhancement of phagocyte function

The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13-dependent mechanisms.