Neurocognitive Outcome and White Matter Anisotropy in Childhood Acute Lymphoblastic Leukemia Survivors Treated with Different Protocols

Neurocognitive outcome affects the quality of life of ALL survivors. This study is aimed to assess the prevalence of neurocognitive dysfunction by psychometric and imaging tools in survivors of childhood ALL, treated with 3 different protocols and the effect of time elapsed since the end of chemotherapy. Sixty-two ALL survivors aged 6–18 years and treated in the period 1997–2007 and 60 healthy age and sex matched controls were subjected to neurocognitive testing using Wechsler Intelligence Scale for Children, Benton visual retention (BVRT) and Trail Making test (TMT), followed by diffusion weighed and diffusion tensor MRI for calculation of fraction anisotropy (FA). Survivors underwent revision of protocol and type of CNS therapy. Three different protocols were used: modified BFM 83, BFM 90, and CCG. Survivors treated with modified CCG protocol showed a significant decrease in all cognitive tests compared to control (p<.05); BFM 90 group had a significant lower IQ and longer TMT compared to both control and BFM 83 group and no significant difference was found in results of cognitive tests between BFM 83 and control group. Frontal FA was lower in CCG treated group compared to control, BFM 90 and BFM 83 groups (p<.05); meanwhile it was significantly lower in BFM 90 and BFM 83 groups compared to control group. We concluded that patients treated with modified CCG protocol showed the worst neurocognitive outcome among three assessed protocols. Frontal lobe FA might be an early marker for predicting the neurotoxicity in childhood ALL survivors.     

Influence of Apical Periodontitis on the Accuracy of 3 Electronic Root Canal Length Measurement Devices: An In Vivo Study

Introduction

The aim of this in vivo study was to evaluate the influence of apical periodontitis (AP) on the accuracy of Dentaport ZX (J Morita, Kyoto, Japan), Raypex 5 (VDW, Munich, Germany), and i-Root (S-Denti, Seoul, Korea) electronic root canal length measurement devices (ERCLMDs).

Methods

Thirty-two single-rooted teeth scheduled for extraction, consisting of 16 teeth with AP and 16 teeth with normal periapex (NP), were selected. The access cavity was prepared, and the coronal portion of the canal was flared. The electronic working length (EWL) was determined by each ERCLMD according to each manufacturer's instructions. Each tooth was extracted, and the actual working length (AWL) was determined by inserting a size 15 K-file until the tip could be seen at a position tangential to the major foramen and then 0.5 mm was subtracted from the measurement. The distance from the file tip (EWL) to the point 0.5 mm coronal to the major foramen (AWL) was calculated. Data were analyzed using the nonparametric Fisher exact test and the chi-square test. Statistical significance was set at P < .05.

Results

The accuracies of Dentaport ZX, Raypex 5, and i-Root within ±0.5 mm in the AP group were 93.8%, 81.3%, and 75.0%; they were 93.3%, 86.7%, and 73.3% in the NP group, respectively. There were no significant differences between the accuracy of each device in the 2 groups (P > .05). Considering the 2 groups of AP and NP, there were no statistically significant differences in the accuracy of the ERCLMDs (P > .05).

Conclusions

The presence of AP did not influence the accuracy of ERCLMDs.     

Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles

Background

Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system.

Methods

The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed.

Results

The particle size of NPs ranged from 170 to 190 nm and increased about 20–30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased further after HSA conjugation. The HSA conjugation in prepared NPs was proved by Fourier transform infrared (FT-IR) spectroscopy, faster degradation of HSA in Differential scanning calorimetry (DSC) characterization, and other evidences such as the increasing in size and the decreasing in zeta potential. The PTX released in a biphasic mode for all colloidal suspensions. A sustained release profile for approximately 33 days was detected after a burst effect of the loaded drug. The in vitro cytotoxicity evaluation also indicated that the HSA NPs are more cytotoxic than plain NPs.

Conclusions

HSA decoration of PLGA NPs may be a suitable method for longer blood circulation of NPs.     

Cationic Albumin‐Conjugated Chelating Agent as a Novel Brain Drug Delivery System in Neurodegeneration

The critical role of metal ions and in particular iron in oxidative stress and protein aggregation offers chelation therapy as a sensible pharmaceutical strategy in oxidative stress‐induced neuronal damages. In this research, we conjugated an iron‐chelating agent, deferasirox, to cationized human serum albumin molecules in order to develop a novel brain delivery system for the management of neurodegenerative disorders due to the significant role of oxidative stress‐induced neuronal injury in such diseases. Cationized albumin is known to be able to transport to brain tissue via adsorptive‐mediated transcytosis. The developed structures were molecularly characterized, and their conjugation ratio was determined. PC12 cell line was utilized to evaluate the neuroprotective features of these newly developed molecules in the presence of hydrogen peroxide neuronal damage and to identify the mechanisms behind the observed neuronal protection including apoptotic and autophagic pathways. Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the impact of conjugated structures in vivo. Data analysis revealed that the conjugated species were able to hinder apoptotic cell death while enhancing autophagic process. The developed conjugated species were also able to attenuate amyloid beta‐induced learning deficits when administered peripherally.     

Randomized controlled trial of bilateral intrapleural block in cardiac surgery

The aim of this study was to determine the efficacy of bilateral intrapleural block with bupivacaine as a preemptive analgesic for postoperative pain in coronary artery bypass graft surgery. In a double-blind prospective clinical trial, 70 patients were randomly divided into a bupivacaine group (20 mL bupivacaine 0.25% and 0.5 mL adrenaline 1/200,000 each side) and a control group (20.5 mL normal saline each side). Evaluation of the severity of pain was performed using the visual analog scale at 12 and 24 h after entering the intensive care unit and again during chest tube removal. Pain scores at 12 and 24 h after intensive care unit admission were significantly lower in the bupivacaine group. There were no side-effects related to intrapleural block, such as pneumothorax or emphysema. In coronary artery bypass graft candidates, preemptive analgesia with bilateral intrapleural block using bupivacaine provided relatively less painful conditions during the first 24 h after surgery, but it did not improve the clinical outcome.     

Phenotypic Assays to Determine Virulence Factors of Uropathogenic Escherichia coli (UPEC) Isolates and their Correlation with Antibiotic Resistance Pattern

Objectives

Urinary tract infection caused by uropathogenic Escherichia coli (UPEC) strains is one of the most important infections in the world. UPEC encode widespread virulence factors closely related with pathogenesis of the bacteria. The purpose of this study was to evaluate the presence of different phenotypic virulence markers in UPEC isolates and determine their correlation with antibiotic resistance pattern.

Methods

UPEC isolates from patients with different clinical symptoms of UTI were collected and screened for biofilm and hemolysin production, mannose resistant, and mannose sensitive hemagglutination (MRHA and MSHA, respectively). In addition, antimicrobial resistance pattern and ESBL-producing isolates were recorded.

Results

Of the 156 UPEC isolates, biofilm and hemolysin formation was seen in 133 (85.3%) and 53 (34%) isolates, respectively. Moreover, 98 (62.8%) and 58 (37.2%) isolates showed the presence of Types 1 fimbriae (MSHA) and P fimbriae (MRHA), respectively. Our results also showed a relationship between biofilm formation in UPEC isolated from acute cystitis patients and recurrent UTI cases. Occurrence of UTI was dramatically correlated with the patients'' profiles. We observed that the difference in antimicrobial susceptibilities of the biofilm and nonbiofilm former isolates was statistically significant. The UPEC isolates showed the highest resistance to ampicillin, tetracycline, amoxicillin, and cotrimoxazole. Moreover, 26.9% of isolates were ESBL producers.

Conclusion

This study indicated that there is a relationship between the phenotypic virulence traits of the UPEC isolates, patients'' profiles, and antibiotic resistance. Detection of the phenotypic virulence factors could help to improve understanding of pathogenesis of UPEC isolates and better medical intervention.