The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.

Predictors of personal recovery for individuals with schizophrenia spectrum disorders living in the community.

INTRODUCTION: Personal recovery is a complex construct frequently used as outcome measure in people with schizophrenia spectrum disorders. This study examined potential predictors of personal recovery using the two most common assessment tools for people with schizophrenia spectrum disorders living in the community: the Chinese version of the Questionnaire about the Process of Recovery and the Chinese version of the Recovery Assessment Scale. METHODS: Ninety-one individuals (57 women) diagnosed with schizophrenia spectrum disorders participated in the study (mean age: 47.41 ± 9.41 years). All participants lived in the community and received community psychiatric services. The participants were evaluated via interviews, questionnaires and standardized assessments. Potential predictors included four domains: personal, disease-related, functional and social. Stepwise multiple linear regression was used to analyse the potential predictors of the recovery and recovery assessment scale. RESULTS: Resilience and social support were the only significant predictors of the Chinese versions of the Questionnaire about the Process of Recovery and Chinese version of the Recovery Assessment Scale. The primary predictor of the Chinese version of the Questionnaire about the Process of Recovery was social support from family and institutional staff. Conversely, resilience was the major predictor of the Chinese version of the Recovery Assessment Scale. DISCUSSION: For people with schizophrenia spectrum disorders living in the community, social support and resilience significantly predicted personal recovery. Age, educational level, disease-related and functional factors were not significant predictors of personal recovery. Therefore, it is important to develop successful personal recovery-oriented practices that enhance resilience and promote social support.

Prophylactic clipping after endoscopic mucosal resection of large nonpedunculated colorectal lesions: A meta-analysis.

BACKGROUND AND AIM: It is not clear whether prophylactic clipping after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions (LNPCLs) prevents delayed bleeding (DB). We aimed to conduct a meta-analysis to clarify the efficacy of prophylactic clipping in prevention of DB following EMR of LNPCLs. METHODS: We searched PubMed, EMBASE, Web of Science, ScienceDirect, Cochrane Library databases, and ClinicalTrials.gov for studies that compared clipping versus (vs) nonclipping in prevention of DB following EMR of LNPCLs. Pooled odds ratio (OR) was determined using a random effects model. The pooled ORs of DB, perforation, and post-polypectomy syndrome in the clipping group compared with the nonclipping group comprised the outcomes. Subgroup analyses based on study design, polyp location, and completeness of wound closure were performed. RESULTS: Five studies with a total of 3112 LNPCLs were extracted. Prophylactic clipping reduced the risk of DB compared with nonclipping (3.3% vs 6.2%, OR: 0.494, P = 0.002) following EMR of LNPCLs. In subgroup analysis, prophylactic clipping reduced DB of LNPCLs at proximal location (3.8% vs 9.8%, P = 0.029), but not of them at distal location (P = 0.830). Complete wound closure showed superior efficacy to prevent DB compared with partial closure (2.0% vs 5.4%, P = 0.004). No benefit of clipping for preventing perforation or post-polypectomy syndrome was observed (P = 0.301 and 0.988, respectively). CONCLUSIONS: Prophylactic clipping can reduce DB following EMR of LNPCLs at proximal location. Besides, complete wound closure showed superior efficacy to prevent DB compared with partial closure. Further cost analyses should be conducted to implement the most cost-effective strategies.

Risk of Parkinson's disease among patients with herpes zoster: a nationwide longitudinal study.

OBJECTIVE: Several studies suggested a potential role of viral infection in the pathophysiology of Parkinson's disease (PD). However, the association between herpes zoster and PD was not investigated well till now. METHODS: Using the Taiwan National Health Insurance Research Database, 13 083 patients aged ≥45 years with herpes zoster and 52 332 (1:4) age-/sex-matched controls were enrolled between 1998 and 2008 and followed to the end of 2011. Those who developed PD during the follow-up period were identified. RESULTS: The Cox regression analysis with adjustment of demographic characteristics, health system utilization, and comorbidities demonstrated that patients with herpes zoster had an increased risk (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.43-2.28) of developing PD in later life compared to the control group. Sensitivity tests after excluding the first year (HR: 1.50, 95% CI: 1.16-1.93) and first 2-year (HR: 1.44, 95% CI: 1.10-1.88) observation periods showed consistent results. CONCLUSIONS: Patients with herpes zoster were more likely to develop PD in later life compared to the controls. Additional studies are necessary for validating our results and to clarify the underlying pathophysiology between herpes zoster and PD.

Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF-κB-mediated IKKß expression.

We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression. TWIST1 messenger RNA levels positively associated with COL11A1 messenger RNA expression levels in ovarian tumors. High TWIST1 expression levels were significantly associated with a progression-free interval of ≤ 6 months (p = 0.001) and death (p = 0.040). In addition, patients with high TWIST1 mRNA levels had significantly shorter 5-year overall-survival (p = 0.004) and progression-free survival (p = 0.009) rates, compared to patients with low TWIST1 levels. Increased TWIST1 expression caused by COL11A1-induced transcription of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) gene occurred via increased SP1 phosphorylation and binding to the IKKß promoter. COL11A1-mediated nuclear factor-kappa B activation, via transcriptional activation of IKKß, promoted TWIST1, Mcl-1, and GAS6 expression, which were associated with chemoresistance and anti-apoptosis in ovarian cancer cells. We suggest that IKKß and TWIST1 can potentially be targeted in patients with COL11A1-positive ovarian cancer.

Risk of Epilepsy in Individuals With Posttraumatic Stress Disorder: A Nationwide Longitudinal Study.

OBJECTIVE: Several cross-sectional studies have reported a relationship between posttraumatic stress disorder (PTSD) and epilepsy. However, the temporal association between PTSD and epilepsy has rarely been investigated. We hypothesized that the risk of developing epilepsy later in life would be higher in patients with PTSD than in those without PTSD. METHODS: Using the Taiwan National Health Insurance Research Database, 6425 individuals with PTSD and 24,980 age-/sex-matched controls were enrolled between 2002 and 2009 in our study and followed up to the end of 2011. Those who developed epilepsy during the follow-up period were identified. RESULTS: Individuals with PTSD had a higher incidence of developing epilepsy (2.65 versus 0.33 per 1000 person-years, p < .001), with an earlier onset of epilepsy (37.53 years [15.80 years] versus 48.11 years [23.97 years], p = .002) than did the controls. Individuals with PTSD had an elevated risk of developing epilepsy (hazard ratio [HR] = 3.72, 95% confidence interval [CI] = 2.27-6.11) during the follow-up after adjustment for demographic data and medical and psychiatric comorbidities. Sensitivity analyses after excluding the observation in the first year (HR = 2.53, 95% CI = 1.44-4.47) and the first 3 years (HR = 2.14, 95% CI = 1.15-4.01) revealed consistent results. CONCLUSIONS: These results supported a temporal association between PTSD and the development of epilepsy. Further studies are warranted to investigate the underlying pathophysiological pathways that explain the longitudinal association of PTSD with subsequent epilepsy.

Enhanced Fano resonance in a non-adiabatic tapered fiber coupled with a microresonator.

We achieved enhanced Fano resonance by coupling a bottle resonator with a special non-adiabatic tapered fiber, where there is a high intensity distribution ratio between high-order and fundamental modes in the tapered region, as well as single mode propagation in the waist region. The resonance line shape is theoretically proved to be related to the intensity distribution ratio of the two fiber modes and their phase shift. An enhanced Fano line shape with an extinction ratio over 15 dB is experimentally reached by improving the intensity distribution ratio and tuning the phase shift. The results can remarkably improve the sensitivity of whispering-gallery mode microresonators in the field of optical sensing.

Coupled-mode induced transparency in a bottle whispering-gallery-mode resonator.

Whispering-gallery-mode (WGM) optical resonators are ideal systems for achieving electromagnetically induced transparency-like phenomenon. Here, we experimentally demonstrate that one or more transparent windows can be achieved with coupled-mode induced transparency (CMIT) in a single bottle WGM resonator due to the bottle's dense mode spectra and tunable resonant frequencies. This device offers an approach for multi-channel all-optical switching devices and sensitivity-enhanced WGM-based sensors.

Encoded error calibration for a coded aperture spectrometer based on deconvolution.

The principle of a 2D coded aperture spectrometer is described in this paper. The crosstalk of adjacent rows, which is caused by the optical system's point-spread function and the nonuniform illumination of the apertures, is the main source of the system decoded errors. Through the analysis of the effect of the crosstalk and nonuniform illumination on the decoded spectrum, the encoding matrix is modified. Based on the new encoding equation, an algorithm using Gold's deconvolution method is proposed to remove the crosstalk of adjacent rows. In the end, we evaluate the effect of this method through a series of contrast experiments.

[Application of the Peak Area Ratio of STR Loci to Amelogenin Locus in the Estimation of DNA Degradation].

OBJECTIVE: To explore the change rules of peak area ratio of STR loci to Amelogenin (AMEL) locus (STR/AMEL), a sex-determining gene in DNA degradation, and to evaluate the application of STR/AMEL value in the estimation of DNA degradation degree. METHODS: DNA was extracted from iliopsoas, and the variations of STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) were analyzed after the artificial degradation was made by DNase I, and the changes of these three ratios of the iliopsoas naturally degraded in an outdoor environment were also analyzed. The regression curves were analyzed using the periods of DNA degradation and outside the body as the independent variable (x) and the STR/AMEL value as the dependent variable (y) and three curve equations under two conditions were established. RESULTS: Both under the conditions of artificial and natural degradation, STR/AMEL value had a negative relationship with the degradation time. The relationship between STR/AMEL and degradation time can be well simulated by the cubic function. R2 was over 0.99 under controlled degradation condition and over 0.86 under natural degradation condition. CONCLUSION: The STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) is negatively related with the DNA degradation degree, which follows mathematical regression models strictly, and it might be applied to evaluate the DNA degradation degree.

All-trans retinoic acid downregulates ALDH1-mediated stemness and inhibits tumour formation in ovarian cancer cells.

Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem-like cell (CSC) marker in human cancers; however, the specific ALDH1-regulated function and its underlying signalling pathways have not been fully demonstrated. Here, we investigated the ALDH1-regulated function and its underlying signalling and tested whether all-trans retinoic acid (ATRA) can suppress ALDH1-regulated tumour behaviour in ovarian cancer cells. By modulating ALDH1 expression using flow cytometry enrichment and exogenous overexpression or knockdown, we showed that the ALDH1 activity is positively correlated with stemness in ovarian cancer cells according to measures such as sphere formation and CSC marker expression as well as tumourigenesis in a mouse xenograft model. The findings indicate that the ALDH1 directly regulates the functions of ovarian cancer cells. We also showed that ALDH1 can regulate the expression of FoxM1 and Notch 1, which are involved in the downstream signalling of ALDH1-mediated biofunctions. Inhibition of FoxM1 by Thiostrepton and of Notch1 by DAPT downregulated the sphere formation ability of cells. ATRA reduced ALDH1 expression, suppressed tumour formation and inhibited sphere formation, cell migration and invasion in ALDH1-abundant ovarian cancer cells. We conclude that ATRA downregulates ALDH1/FoxM1/Notch1 signalling and suppresses tumour formation in ovarian cancer cells.

Analysis of thermo-optic effect-based refractive index dynamic modulation in microspherical resonator.

The thermo-optic effect has been utilized to modulate the refractive index dynamically within a whispering gallery mode resonator. Modulation with a large tuning range is mostly performed for mode locking and dynamic control of the optical path at a modulation frequency as low as several hertz, while high-frequency modulation up to megahertz is mainly exploited in optical switching devices with small tuning range. Here, we introduce the response functions theoretically to describe the dynamic response of temperature changes in the mode volume and the resonator body, respectively. This result is verified experimentally in silica microspherical resonators. The dependence of the tuning range on the modulation frequency is achieved. This knowledge could pave the way toward more practical control of refractive index in microresonators.

Risk of epilepsy among patients with atopic dermatitis: a nationwide longitudinal study.

OBJECTIVE: Both atopic dermatitis and epilepsy have been regarded as chronic inflammatory diseases. However, their association has yet to be investigated. METHODS: Using the Taiwan National Health Insurance Research Database, 35,312 patients with atopic dermatitis but without a history of epilepsy, and 35,312 age-/gender-matched controls were enrolled between 1998 and 2008, and followed to the end of 2011 to identify the development of epilepsy. RESULTS: Subjects with atopic dermatitis had a higher incidence of developing epilepsy (0.94 vs. 0.27/1,000 person-years, p < 0.001) than the control group. The Cox regression model showed that atopic dermatitis increased the risk of developing epilepsy (hazard ratio [HR] 2.91, 95% confidence interval [CI] 2.23-3.82) after adjusting for demographic data and medical comorbidities. Sensitivity tests showed consistent findings (HR 2.32, 95% CI 1.68-2.96) after excluding the first year of observation. In addition, asthma (HR 1.34, 95% CI 1.04-1.72) and allergic rhinitis (HR 1.34, 95% CI 1.04-1.73) were related to the risk of epilepsy. SIGNIFICANCE: Subjects with atopic dermatitis were associated with an increased risk of developing epilepsy in later life. Further studies would be needed to investigate the underlying mechanisms.

The role of Sequence Type (ST) 131 in adult community-onset non-ESBL-producing Escherichia coli bacteraemia.

BACKGROUND: To compare the epidemiological and clinical features and outcome in clonal group O25b/ST131 and non-clonal group O25b/ST131 in adult patients with non-extended-spectrum B-lactamase (ESBL)-producing Escherichia coli (E. coli) bacteraemia. METHODS: We collected 371 consecutive isolates with community-onset non-ESBL producing E. coli bloodstream infection in 2010 in a 1200-bed hospital in Taiwan. Twenty adult patients with clonal group O25b/ST131 and 40 patients with non-clonal group O25b/ST131 were compared. RESULT: Clonal group O25b/ST131 accounted for 5.9% of total isolates. The underlying disease and healthcare-associated risk factors were similar in the case and control groups. Patients with the clonal group O25b/ST131 were less likely to have intra-abdominal infection (0% vs. 22.5%; p < 0.05) than patients from the control group. The Day 30 mortality rate was similar in the case and control groups (15% vs. 12.5%). CONCLUSIONS: Clonal group O25b/ST131 was found in both multidrug-resistant and susceptible E. coli strains, causing community-onset bloodstream infection. Although O25b/ST131 does not lead to a higher mortality than other isolates, choosing an appropriate antimicrobials in the empirical therapy of community-onset E. coli bacteraemia has become more challenging.

Clostridium difficile ribotype 126 in southern Taiwan: a cluster of three symptomatic cases.

INTRODUCTION: Several virulent Clostridium difficile clones, designated as polymerase chain reaction (PCR) ribotypes 017, 027, or 078, are well recognized in western countries. However, the ribotype distribution of clinical C. difficile isolates in Taiwan remains unclear. METHOD: Between 2010 and 2012, we identified three patients with C. difficile-associated diarrhea (CDAD) at a hospital in southern Taiwan. The C. difficile strains isolated from these patients were further characterized by PCR detection of tcdA, tcdB, tcdC, cdtA, and cdtB, toxinotyping, multilocus sequence typing, ribotyping and repetitive-based PCR. RESULTS: Three C. difficile strains harbored tcdCΔ39 and belonged to multilocus sequence typing 11 (ST11), toxinotype V, and ribotype 126 (a ribotype 078-like clone). Notably, one patient developed pseudomembranous colitis and recurrent CDAD. These three isolates were noted between January 2012 and June 2012 and were identical, as evidenced by repetitive sequence-based PCR, suggestive of case clustering. CONCLUSION: A hypervirulent C. difficile clone, ribotype 126, causing pseudomembranous colitis and recurrent CDAD, is present in southern Taiwan.

Vancomycin-resistant Clostridium innocuum bacteremia following oral vancomycin for Clostridium difficile infection.

An 85 year-old male initially admitted for septic shock due to urinary tract infection experienced Clostridium difficile-associated diarrhea during hospitalization and was treated by oral vancomycin. His clinical course was complicated by cytomegalovirus colitis and then vancomycin-resistant Clostridium innocuum bacteremia, which was cured by uneventfully parenteral piperacillin-tazobactam therapy.

[1H-MRS study on the metabolites of first dorsal interossei].

OBJECTIVE: To estimate the application of prognosis evaluation of ulnar nerve injury by 1H-magnetic resonance spectroscopy (1H-MRS). METHODS: The metabolites of first dorsal interossei (FDI) of two hands from 12 healthy volunteers and 1 volunteer with complete ulnar nerve injury were detected by 1H-MRS and the data were statistically analyzed. RESULTS: For the FDI of healthy adults, the female peaks area of extra-myocellular lipids (EMCL) was higher than the male (P < 0.05); There was no significant difference in Cho, Cr and intra-myocellular lipids (IMCL) between male and female (P > 0.05); There was no significant difference in all the peaks area between the left and right hand (P > 0.05). The EMCL peak of the injury side was higher than that of the healthy side, and the area of FDI was reduced in the volunteer with ulnar nerve injury. CONCLUSION: Noninvasive and quantitative detection of 1H-MRS may be valuable for prognosis evaluation of peripheral nerve injury.

Removal of electrical stimulus artifact in local field potential recorded from subthalamic nucleus by using manifold denoising.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders such as Parkinson's disease (PD). However, local field potentials (LFPs) recorded through lead externalization during high-frequency stimulation (HFS) are contaminated by stimulus artifacts, which require to be removed before further analysis. NEW METHOD: In this study, a novel stimulus artifact removal algorithm based on manifold denoising, termed Shrinkage and Manifold-based Artifact Removal using Template Adaptation (SMARTA), was proposed to remove artifacts by deriving a template for each stimulus artifact and subtracting it from the signal. Under a low-dimensional manifold assumption, a matrix denoising technique called optimal shrinkage was applied to design a similarity metric such that the template for stimulus artifacts could be accurately recovered. RESULT: SMARTA was evaluated using semirealistic signals, which were the combination of semirealistic stimulus artifacts recorded in an agar brain model and LFPs of PD patients with no stimulation, and realistic LFP signals recorded in patients with PD during HFS. The results indicated that SMARTA removes stimulus artifacts with a modest distortion in LFP estimates. COMPARISON WITH EXISTING METHODS: SMARTA was compared with moving-average subtraction, sample-and-interpolate technique, and Hampel filtering. CONCLUSION: The proposed SMARTA algorithm helps the exploration of the neurophysiological mechanisms of DBS effects.

[Study on the wavelength accuracy of the 2-D slit-array Hadamard spectrometer].

The 2-D slit array mask is a new design of Hadamard spectrometer mask. Having discussed the influence of the inconsistency caused by the machining errors in the size and location between the slits in the same column on the wavelength accuracy of the Hadamard spectrometer, the authors bring up with the way to decrease the influence on the wavelength accuracy of the spectrometer caused by the difference in the height and location vertical to the spectrum between the slits in the same column, and then estimate the spectral shift caused by the relative location shift along the spectrum between the slits in the same column. A model for simulation was built, and the measurement errors in the decoded spectrum generated by one column of the slits on the mask were calculated, when there are inconsistency errors in width and location along the spectrum between the slits in another column. Based on the simulation calculation, we can determine the machining precision of the mask. The research will be meaningful to the design of the 2-D slit array mask using MEMS(micro-electro-mechanism system) technique and the revise of the decoded spectrum, which can provide the spectrometer with a reasonable wavelength accuracy.

Design of Dual-Configuration Dual-Mode Stimulator in Low-Voltage CMOS Process for Neuro-Modulation.

A dual-configuration dual-mode stimulator for neuro-modulation is proposed and designed. All the electrical stimulation patterns that frequently used for neuro-modulation can be generated by the proposed stimulator chip. Dual-configuration represents the bipolar or monopolar structure, meanwhile dual-mode stands for the current or voltage output. No matter what stimulation circumstance is chosen, biphasic or monophasic waveforms can be fully supported by the proposed stimulator chip. The stimulator chip with 4 stimulation channels has been fabricated in 0.18-µm 1.8-V/3.3-V low-voltage CMOS process with common grounded p-type substrate, which is suitable for SoC integration. The design has conquered the overstress and reliability issues in the low-voltage transistors under the negative voltage power domain. Each channel in the stimulator chip only occupies the silicon area of 0.052 mm2, and the maximum output level of stimulus amplitude is up to ±3.6 mA and ±3.6 V. With the built-in discharge function, bio-safety concern of unbalanced charge in neuro-stimulation can be dealt with properly. Moreover, the proposed stimulator chip has been applied on both imitation measurement and in-vivo animal test successfully.