This special edition of the Biomedical Journal focuses on experimental autoimmune encephalomyelitis, and includes three reviews showing how this model has greatly facilitated our understanding of the pathophysiology of multiple sclerosis. We also highlight a small single center study which suggests that the use of calcium bone substitutes during core decompression surgery may do more harm than good. Finally, we see how policy changes affect the management of fungal infections in immunocompromised patients and we learn about antibiotic resistance among strains of Streptococcus agalactiae circulating in Taiwan.

T cells are major initiators and mediators of disease in multiple sclerosis (MS) and in its animal model experimental autoimmune encephalomyelitis (EAE). EAE is an antigen-driven autoimmune model in which immunization against myelin autoantigens elicits strong T cell responses which initiate its pathology with CNS myelin destruction. T cells cause pathogenic events by several mechanisms; some work in a direct fashion in the CNS, such as direct cytokine-induced damage, granzyme-mediated killing, or glutamate-induced neurotoxicity, whereas most are indirect mechanisms, such as activation of other cell types like macrophages, B cells, or neutrophils. This review aims to describe and discuss the molecular effector mechanism by which T cells harm the CNS during EAE.

A growing body of evidence from basic and clinical studies supports the therapeutic potential of estrogens in multiple sclerosis (MS), originating from the well-established reduction in relapse rates observed among women with MS during pregnancy. The biological effects of estrogens are mediated by estrogen receptors (ERα and ERβ). Estrogens or selective ER-agonists have been shown to exert potent neuroprotective or anti-inflammatory effects in experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. A central question in EAE is to identify the cellular targets that express a functional ER isotype, and the mechanisms underlying the neuroprotective and anti-inflammatory effects of estrogens. Using pharmacological approaches targeting ER-specific functions, and genetic tools such as conditional knockout mice in which ERα or ERβ are selectively deleted in specific cell populations, a clearer picture is now emerging of the various cellular targets and downstream molecules responsible for estrogen-mediated protection against central nervous system autoimmunity.

We now have potent drugs available to treat the inflammatory component of multiple sclerosis (MS). However, not all patients respond, the drugs are not curative, and the associated risks to beneficial immune surveillance are considerable. A more desirable approach is to specifically target those comparatively rare T lymphocytes that are orchestrating the autoimmune attack. Using the autoantigen itself to instill immune tolerance in those cells remains a holy grail of immunotherapy. Peptide immunotherapy (PIT) is highly effective at silencing autoimmune responses in experimental autoimmune encephalomyelitis (EAE), and clinical trials of PIT are underway in MS. This review discusses the current paradigms for PIT-induced tolerance in naïve T cells. It highlights the need for better understanding of the mode of action of PIT upon memory and effector T cells that are responsible for driving/sustaining ongoing autoimmune pathology. Recent studies in EAEsuggest genetic and epigenetic changes in these pathogenic T-cell populations in response to PIT. Finally, future challenges to effective translation of PIT to the clinic are considered.

Background: Antimicrobial resistance of Streptococcus agalactiae (Group B Streptococcus, GBS) has been emerging worldwide. We aimed to examine the correlation of drug-resistant genes with serotypes and with the mutations of the quinolone resistance-determining region (QRDR) in GBS isolates. Methods: A total of 323 human GBS isolates were collected from a hospital in southern Taiwan. Laboratory investigation included serotyping by a multiplex polymerase chain reaction (PCR) method, antimicrobial susceptibility testing by a disc diffusion method, and mechanism analysis of the resistance to macrolides and fluoroquinolones by PCR and sequencing methods. Results: Multiplex PCR showed that the most prevalent serotypes were Ib, III, V, and VI, mostly isolated from urine. The ermB gene was highly prevalent in serotypes Ib and V and was associated with clindamycin and macrolide resistance. GBS with a serine-to-leucine mutation at codon 81 in GyrA and with a serine-to-phenylalanine or -tyrosine mutation at codon 79 in ParC had a higher minimum inhibitory concentration of levofloxacin than isolates with only an aspartic acid-to-tyrosine mutation at codon 83 (>32 μg/ml vs. 16 μg/ml) in GyrA. Conclusions: The most prevalent GBS serotypes were Ib, III, V, and VI. The ermB and mefE genes carried in serotypes Ib and V were highly associated with the resistance to macrolides and clindamycin. Mutations at codon 79 and codon 83 of ParC were the major determining factors for high-level fluoroquinolone resistance.

Background: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are still ill-defined. Methods: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT) scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS), overall survival (OS), and toxicity profile were assessed prospectively. Results: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4%) achieved partial response (PR). Twenty-one patients (21/39, 53.8%) had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29). Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months) and OS (18.3 months) of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively). But the survival differences were statistically non-significant. Conclusions: A very high percentage (72.4%, 21/29) of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

Background: Poincare plots are commonly used to study the nonlinear behavior of physiologic signals. The aim of this study is to evaluate the Poincare plot indices of human heart rate signals during meditation. Methods: For this purpose, heart rate time series of eight Chi meditators available in Physionet database were used. Poincare plots with lags of 1 and 6 were constructed, and the ratio of the minor axis to major axis (SD1/SD2) and the area of Poincare plots were calculated for each lag. Results: The results show that the SD1/SD2 ratio increased significantly during meditation compared to that before meditation, especially the index measured from Poincare plots reconstructed with a lag of 6 (p < 0.05). In addition, in both lags, the area of Poincare plots decreased significantly during meditation compared to before meditation (p < 0.05). Conclusion: The comparative dynamic measures of the Poincare plot indices during and before meditation give more insight of the heart rate signals in a specific psychophysiological state.

Background: Invasive fungal infections (IFIs) remain one of the worrying complications in patients with acute myeloid leukemia (AML) due to their incidence and high level of attributable mortality. In light of these risks, antifungal prophylaxis has always been debated. We conducted a single-center retrospective study of two prophylactic antifungal agents (fluconazole/posaconazole) in 91 consecutive patients receiving induction chemotherapy for AML between 2005 and 2009, in order to evaluate the impact on the incidence of IFI and on the mycological flora of the patients. Methods: In total, 39 patients received prophylactic fluconazole versus 52 who received posaconazole. The baseline characteristics of the two groups were comparable. Results: Overall, 17 patients developed an IFI, with no difference in frequency between the two groups. Utilization of empirical or pre-emptive therapy was similar irrespective of the type of prophylaxis used. Mycological examination of stools revealed an increase in non-albicans Candida colonization in the fluconazole group during hospitalization and the appearance of Saccharomyces cerevisiae colonization in patients receiving posaconazole. Conclusion: The present study does not distinguish between fluconazole and posaconazole as a primary effective prevention against fungal infections. More prospective studies and meta-analyses are warranted.

Background: Proper function, esthetics, and cost are the prime factors to be considered while selecting bridge veneering materials. The purpose of the study is to evaluate color durability of acrylic veneer materials after immersion in common beverages at different time intervals. Methods: Spectrophotometer was used for taking color measurements based on the transmission of light through the specimens made of the selected materials which were Tooth moulding powder (DPI) and Acrylux (Ruthinium). Thirty specimens of standardized dimensions were prepared from each material. The specimens were divided into three groups of 10 each. One group of each material was immersed in tea (TajMahal) and another group of each material in cola (Pepsi) as the staining solutions. The remaining group of 10 from each material served as control and was stored in distilled water. Color measurements were obtained pre-immersion, and after 1, 15, and 30 days of immersion. Results: Tooth moulding powder displayed better color durability than Acrylux over the 1 month immersion period in both staining solutions. Tea resulted in more discoloration compared to cola (Pepsi). Conclusion: The difference in the color durability of Acrylux and Tooth moulding powder may be attributed to the differences in the composition of tested resin veneering materials, i.e. their polar properties, which contribute to the absorption of staining solution, and the different brands and the strengths of the solutions.

Background: Hepatitis B virus (HBV) infection is one of the infections with a highest prevalence in Taiwan. The most important marker is hepatitis B surface antigen (HBsAg). Using the new generation of HBsAg quantitative assay, HBsAg level may have good correlation with viral activity during different phases of chronic hepatitis B virus infection. This study was conducted to compare two assays of HBsAg level to find if the same results are obtained in HBsAg quantification in treatment-naïve and on-treatment chronic hepatitis B patients. Methods: Between March 2012 and June 2012, 90 patients with chronic hepatitis B (68 males and 22 females) were assessed using Abbott Architect HBsAg QT and Roche Elecsys HBsAg II assay. HBV DNA was detected by Roche COBAS TaqMan instrument. Results: HBsAg level measured with Elecsys and Architect assays correlated well in untreated patients (n = 53, γ_s = 0.997) and on-treatment patients (n = 37, γ_s = 0.988). Bland-Altman analyses of the discrepancies in HBsAg levels showed a bias of –4.2% in untreated patients and –6.2% in on-treatment patients. Patients with HBeAg-postive chronic hepatitis B had higher HBsAg level than the ones who were HBeAg negative, and both showed statistical differences. Further, HBV DNA concentration analysis also showed higher viral concentration in HBeAg-positive patients, but it revealed no statistical difference. Conclusions: There is a significant correlation between Abbott Architect HBsAg QT assay and Roche Elecsys HBsAg II assay. Moreover, HBsAg quantification may potentially provide complementary information about the deduction of the natural course in chronic hepatitis B infection.

Background: Osteonecrosis of the femoral head can lead to destruction of the hip joint and disabling arthritis in young adults, if left untreated. Among the salvage procedures, core decompression combined with bone graft substitutes is a viable option for joint preservation. The purpose of this study was to review the outcomes of using synthetic bone graft substitute (calcium sulfate and calcium phosphate) for the treatment of late-stage osteonecrosis of the femoral head. Methods: From November 2008 to May 2009, 19 hips in 18 patients with osteonecrosis of the femoral head [6 hips in Association Research Circulation Osseous (ARCO) stage IIC and 13 hips in stage IIIA] were treated with core decompression combined with PRO-DENSE^™ (Injectable Regenerative Graft). The average age of the patients at the time of surgery was 48 years (range 25-67 years). Twelve patients (13 hips) overused alcohol, four patients (4 hips) were idiopathic, one patient (1 hip) used corticosteroids, and one patient (1 hip) was post-traumatic. The clinical failure was defined as conversion to total hip arthroplasty or progression in head collapse. Results: At the conclusion of the study, 3 in the 6 stage IIC hips and 8 in the 13 stage IIIA hips were converted to total hip arthroplasty in an average of 8.5 months (range 4-30 months) postoperatively. Advanced collapse of the femoral head awaiting for total hip arthroplasty was observed in the other six hips. Of the 19 hips, only 2 hips (10.5%) survived without further collapse in the 5-year follow-up. This resulted in 89.5% failure rate with early resorption of the grafting in an average of 5.3 months. Conclusions: Core decompression combined with an injectable calcium sulfate and calcium phosphate composite graft (PRO-DENSE) were associated high failure rates in the early postoperative period. It is not recommended for the treatment of ARCO stage IIC and IIIA osteonecrosis of the femoral head.

Background: Treatment by posterolateral fusion (PLF) with pedicle-screw instrumentation can be unsuccessful in one-segment and low-grade lumbar spondylolisthesis. Segmental kyphosis, either rigid or dynamic, was hypothesized to be one of the factors interfering with the fusion results. Methods: From 2004 to 2005, 239 patients with single-segment and low-grade spondylolisthesis were recruited and divided into two groups: Group 1 consisting of 129 patients without segmental kyphosis and group 2 consisting of 110 patients with segmental kyphosis. All patients underwent instrumented PLF at the same medical institute, and the average follow-up period was 31 ± 19 months. We obtained plain radiographs of the lumbosacral spine with the anteroposterior view, the lateral view, and the dynamic flexion-extension views before the operation and during the follow-ups. The results of PLF in the two groups were then compared. Results: There was no significant difference in the demographic data of the two groups, except for gender distribution. The osseous fusion rates were 90.7% in group 1 and 68.2% in group 2 (p < 0.001). Conclusion: Instrumented PLF resulted in significantly higher osseous fusion rate in patients without segmental kyphosis than in the patients with segmental kyphosis. For the patients with sagittal imbalance, such as rigid or dynamic kyphosis, pedicle-screw fixation cannot ensure successful PLF. Interbody fusion by the posterior lumbar interbody fusion or transforaminal lumbar interbody fusion technique might help overcome this problem.

Neurilemmoma is a benign tumour of nerve sheath origin that can arise from myelinated nerve. The Head and neck is the most frequent site involved and other sites are scalp, face, oral cavity, pharynx, larynx, trachea and ear. Neurilemmoma usually occur as solitary lesions and in association with NF type 2. Malignant transformation is very rare. We report a case of 18 year old male presented with complaint of nasal obstruction and swelling in right side of nose. We discuss the clinical presentation, histologic features, and therapeutic options for such a rare benign lesion.