The mammalian target of rapamycin (mTOR) pathway is an essential cellular signaling pathway involved in a number of important physiological functions, including cell growth, proliferation, metabolism, protein synthesis, and autophagy. Dysregulation of the mTOR pathway has been implicated in the pathophysiology of a number of neurological diseases. Hyperactivation of the mTOR pathway, leading to increased cell growth and proliferation, has been most convincingly shown to stimulate tumor growth in the brain and other organs in the genetic disorder, tuberous sclerosis complex (TSC). In addition, mTOR may also play a role in promoting epileptogenesis or maintaining seizures in TSC, as well as in acquired epilepsies following brain injury. Finally, the mTOR pathway may also be involved in the pathogenesis of cognitive dysfunction and other neurological deficits in developmental disorders and neurodegenerative diseases. mTOR inhibitors, such as rapamycin and its analogs, may represent novel, rational therapies for a variety of neurological disorders.

Ribonucleotide reductases (RNRs) are essential enzymes that catalyze the reduction of ribonucleotides to desoxyribonucleotides, thereby providing the building blocks required for de novo DNA biosynthesis. The RNR function is tightly regulated because an unbalanced or excessive supply of deoxyribonucleoside triphosphates (dNTPs) dramatically increases the mutation rates during DNA replication and repair that can lead to cell death or genetic anomalies. In this review, we focus on Saccharomyces cerevisiae class Ia RNR as a model to understand the different mechanisms controlling RNR function and regulation in eukaryotes. Many studies have contributed to our current understanding of RNR allosteric regulation and, more recently, to its link to RNR oligomerization. Cells have developed additional mechanisms that restrict RNR activity to particular periods when dNTPs are necessary, such as the S phase or upon genotoxic stress. These regulatory strategies include the transcriptional control of the RNR gene expression, inhibition of RNR catalytic activity, and the subcellular redistribution of RNR subunits. Despite class Ia RNRs requiring iron as an essential cofactor for catalysis, little is known about RNR function regulation depending on iron bioavailability. Recent studies into yeast have deciphered novel strategies for the delivery of iron to RNR and for its regulation in response to iron deficiency. Taken together, these studies open up new possibilities to explore in order to limit uncontrolled tumor cell proliferation via RNR.

Biofilms and microbial aggregates are the common mechanisms for the survival of bacteria in nature. In other words, the ability to form biofilms has been regarded as a virulence factor. Microbial biofilms play an essential role in several infectious diseases such as pulp and periradicular pathosis. The aim of this article was to review the adaptation mechanisms of biofilms, their roles in pulpal and periapical pathosis, factors influencing biofilm formation, mechanisms of their antimicrobial resistance, models developed to create biofilms, observation techniques of endodontic biofilms, and the effects of root canal irrigants and medicaments as well as lasers on endodontic biofilms. The search was performed from 1982 to December 2010, and was limited to papers in English language. The keywords searched on Medline were "biofilms and endodontics," "biofilms and root canal irrigation," "biofilms and intra-canal medicament," and "biofilms and lasers." The reference section of each article was manually searched to find other suitable sources of information.

Background: To report the outcome of patients receiving radiotherapy (RT) after radical prostatectomy (RP). Methods: Between May 2001 and December 2008, 53 consecutive cases of prostate adenocarcinoma treated with RP and RT were reviewed. Results: A total of 49 patients were eligible for this study. After a median follow-up of 53 months, the 4-year overall survival (OS) and biochemical progression-free survival (bPFS) for all patients were 91.0% and 68.9%, respectively. According to univariate and multivariate analysis, pre-RT prostate-specific antigen (PSA) was the most significant factor for bPFS. Patients with pre-RT PSA levels of < 0.2 ng/ml and ≧ 0.2 ng/ml had a 4-year bPFS of 83.1% and 52.6%, respectively (p = 0.013). The incidence of chronic rectal toxicity was low, with no grade 3 toxicity reported and grade 2 toxicity found in only 6 patients (12.2%). However, long-term urinary toxicity of grade 2 or higher was found in 24 patients (49.0%). Conclusion: For patients with increasing PSA levels following RP, local RT should be administered prior to biochemical failure (PSA ≧ 0.2), to ensure good bPFS.

Background: Both pelvic fractures and femoral shaft fractures are caused by high-energy injuries. When unstable pelvic fractures and femoral shaft fractures occur concomitantly, the optimal treatment method is controversial. The aim of this study was to establish a reasonable principle for treating such complicated injuries. Methods: Forty patients sustaining unstable pelvic fractures and concomitant femoral shaft fractures were treated in a 7-year period. The initial management of the fractures was started at the emergency service according to the Advanced Trauma Life Support protocol. Unstable pelvic fractures were wrapped by cloth sheets and femoral shaft fractures were immobilized with a splint. Angiography was performed on patients with unstable hemodynamic status. The definitive treatment for combined fractures was performed after stabilizing the hemodynamics. Closed nailing was used for femoral shaft fractures, and pelvic fractures were treated with various techniques. Results: The mortality rate was 12.5% (5/40) during admission. Thirty-three patients were followed up for an average of 32 months (range, 12-76 months). There were 33 cases of unstable pelvic fractures and 36 instances of femoral shaft fractures. The union rate for pelvic fractures was 100% (33/33), while femoral shaft fractures had a 94.4% (34/36) union rate. The average healing time was 3.3 months (range, 1.6-8.1 months) and 4.1 months (range, 2.5-18.2 months) for pelvic and femoral shaft fractures, respectively. After fracture, 34 hips (94%) achieved a satisfactory result in the Harris hip score and 30 knees (83%) achieved a satisfactory result in the Mize knee score. Conclusions: Stabilization of the hemodynamics in patients with combined fractures should be the first aim. Angiography to stop arterial bleeding in the pelvis is often life-saving. The definitive treatment for combined fractures, such as pelvic fractures and femoral shaft fractures, should wait until hemodynamics is stabilized.

Background: To understand the characteristics, ophthalmic outcomes, and risk factors of retinopathy of prematurity (ROP) in patients with birth weight (BW) greater than 1500 g. The applicability of the ROP screening criteria to the Taiwanese population was also examined. Methods: The study included 104 eyes from 54 ROP patients who had BW greater than 1500 g from 1981 to 2008. Demographic information, disease courses, ophthalmic outcomes, and possible systemic risk factors were recorded. The infants were divided into groups of mild and severe ROP for a risk factor analysis. Results: The mean gestational age (GA) of the infants was 31 ± 1.3 weeks, and the mean BW was 1675 ± 249 g. Mild ROP regressed in 94 eyes (90%), and 10 eyes (10%) developed severe ROP. After various treatments, the regression rates for prethreshold or threshold ROP (n = 8) and stage 4 ROP (n = 2) were 100% and 50%, respectively. Forty-eight patients (85%) had at least three associated systemic risk factors. A multiple logistic regression analysis revealed that patients with an intraventricular hemorrhage were found to have an increased chance of developing severe ROP, especially those with BW greater than 1500 g (p = 0.015). There was also a significant association between patients who had severe ROP and an increased risk of having cerebral palsy (CP) at 1.5 years of age (p = 0.013). Conclusion: The majority of patients with BW greater than 1500 g developed mild ROP. However, advanced ROP with poor visual outcome was also encountered in some patients.

Background: After harvesting the fibula flap, pain, sensory disturbance, weakness of donor leg, reduced walking endurance, ankle instability, and lower walking speed had been reported. The aim of this study was to quantitatively assess functional outcome of regular home-based exercise on donor ankle strength, endurance, and walking ability after free fibula flap for mandibular reconstruction. Methods: Fourteen patients were recruited. Objective isokinetic testing and a 6-min walk test (6MWT) were used to evaluate ankle strength/endurance and walking ability, respectively. Results: There was a significant increase in the peak torque of ankle dorsiflexion/foot inversion of the healthy leg and ankle dorsiflexion/foot eversion of the donor leg after exercise (p < 0.05). After home-based exercise, there was reduced asymmetry in the peak torques of ankle dorsiflexion and foot eversion and the total work of foot eversion between the donor and healthy legs. In 6MWT, no significant difference was found between the walking distances before and after exercise. Conclusion: Regular home-based exercise could improve the strength of ankle dorsiflexion and foot eversion of the donor leg, and get more symmetric ankle motor function between the donor and healthy legs.