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Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors.The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures.Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern.This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.

Endoscopic lumbar discectomy has been an alternative for treating lumbar disc herniation. Evidence-based study for the benefit zone of full-endoscopic lumbar discectomy (FELD) is necessary. The study compared the complication risks between the FELD and open discectomy or microdiscectomy.The literature search was from 4 online databases for randomized controlled trials (RCTs) and cohort studies. The meta-analysis of different study designs was conducted separately. Complication rates were considered primary outcomes, and the recurrence and revision rates were considered secondary outcomes.Six RCTs and thirteen cohort studies met the eligibility criteria. The meta-analysis was conducted separately. From the pooled RCT meta-analysis, the overall complication rates of FELD and open discectomy/microdiscectomy were 5.5% and 10.4%, respectively. The moderate-quality evidence suggested that FELD had a lower risk of overall complications (risk ratio [RR] = 0.55, 95% confidence interval [CI] = 0.31-0.98). There was no significant difference in specific complications and recurrence. The analysis of cohort studies revealed no significant difference in overall complications, but there was significant heterogeneity in the results. The risk of dural injury was significantly lower for FELD (RR = 0.46, 95% CI = 0.22-0.96). The pooled meta-analysis from cohort studies suggested a higher risk of transient dysesthesia (RR = 3.70, 95% CI = 1.54-8.89), residual fragment (RR = 5.29, 95% CI = 2.67-10.45), and revision surgeries (RR = 1.53, 95% CI = 1.12-2.08) for FELD.The current evidence showed a lower risk of overall complications for FELD. The quality of evidence was moderate to low, and the risk of bias from the primary literature should be concerned.

A retrospective, population-based study. To identify factors affecting long-term mortality and medical resources use in disabled spinal cord injury (SCI) patients after syringomyelia diagnosis. A National Health Insurance Research Database containing 10,374 patients with SCI. Data recorded between 1997 and 2012 for 376 disabled SCI patients with syringomyelia and 376 characteristics-matched disabled SCI patients without syringomyelia were collected. The index date was the date of syringomyelia diagnosis. Cox proportional hazards regression model was used to investigate the factors affecting 10-year mortality in these patients. Medical resources use was compared for 1 year before and after index date. The survival rate at 10-year follow-up after syringomyelia diagnosis was estimated at 68.6%. The 10-year survival rate was comparable between the two groups. Age ≥ 60 (adjusted hazard ratios (aHR) 4.21, 95% confidence interval (CI) 2.97 to 5.96) and

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX, notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy, in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured −34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC), the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 μg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

Background Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established treatment for patients suffering from trigeminal neuralgia (TN) as a primary modality or for those refractory to medical treatment. However, few existing studies have identified intraoperative parameter or navigation technique that can be used to predict the rates of short-term or long-term pain relief. In this study, we analyzed patient characteristics, intraoperative parameters and technical factors, and postoperative changes in relation to immediate and long-term pain relief. Method This study included a total 252 patients in which 340 RF-TR were performed under the guidance of intraoperative computed tomography (iCT) alone or with magnetic resonance image (MRI) and iCT fusion imaging. Result The immediate pain relief of RF-TR with iCT alone and iCT with MR image guidance with or without cerebrospinal fluid (CSF) outflow were all above 90.4%. The 2-year pain relief rate of RF-TR using iCT alone and iCT with MR images guidance with or without CSF outflow were 47.8%, 39.8%, 71.7%, and 53.9% respectively. Significant factors for 2-year pain relief were CSF outflow, iCT with MR image fusion, non-recurrent TN, and presence of postoperative facial numbness. Conclusion This preliminary study demonstrated foramen ovale cannulation under the aid of iCT with MR image guidance could improve 2-year pain relief.

The benefits of diploidy are considered to involve masking partially recessive mutations and increasing genetic diversity. Here, we review new studies showing evidence for diverse allele-specific expression and epigenetic states in mammalian brain cells, which suggest that diploidy expands the landscape of gene regulatory and expression programs in cells. Allele-specific expression has been thought to be restricted to a few specific classes of genes. However, new studies show novel genomic imprinting effects that are brain-region-, cell-type- and age-dependent. In addition, novel forms of random monoallelic expression that impact many autosomal genes have been described in vitro and in vivo. We discuss the implications for understanding the benefits of diploidy, and the mechanisms shaping brain development, function, and disease.

Background Identification of small pulmonary nodules is challenging in a limited intrathoracic field during minimally invasive video‐assisted thoracoscopic surgery (VATS), and preoperative localization is required. Various techniques have been reported with some failure and complications. Here, we compare the feasibility and safety between electromagnetic navigation bronchoscopic marking and computed tomography (CT)‐guided percutaneous marking using indocyanine green (ICG) and iopamidol. Methods A total of 47 patients with small‐sized pulmonary nodules, scheduled to undergo video‐assisted thoracoscopic limited resection, were enrolled in this study. A mixture of diluted ICG and iopamidol was injected into the lung parenchyma as a marker, using CT‐guided percutaneous or electromagnetic navigation bronchoscopic injection techniques and the results were examined and compared. Results A total of 35 and 12 patients underwent preoperative marking by percutaneous injection and electromagnetic navigation bronchoscopic injection, respectively, in which a marker was detected in 33/35 (94.3%) and 12/12 (100%) patients. No combination of these procedures was performed in any patient. All markers were successfully detected in three patients who underwent injection marking at two different lesion sites. Pneumothorax occurred in five patients (14%) in the percutaneous marking group, which was relieved in all patients without the necessity for chest tube drainage. No other complication was observed in this study. Conclusions Electromagnetic navigation bronchoscopic injection techniques using indocyanine green fluorescence plus iopamidol are safe and effective, and comparable with CT‐guided localization. Furthermore, a bronchoscopic approach enables marking of multiple lesion areas without increasing patient risk, especially for puncture‐related pneumothorax. Key points Significant findings of the study Either computed tomography (CT)‐guided percutaneous or electromagnetic navigation bronchoscopic injection techniques can be used for preoperative marking of pulmonary nodules with indocyanine green (ICG) fluorescence. What this study adds Indocyanine green (ICG) is a safe and easily detectable fluorescent marker for video‐assisted thoracoscopic surgery (VATS).A bronchoscopic injection approach enables marking of multiple lesion areas without increasing the risk of pneumothorax., Computed tomography (CT)‐guided percutaneous or electromagnetic navigation bronchoscopic injection techniques can be used for preoperative marking of pulmonary nodules with indocyanine green (ICG) fluorescence. ICG is a safe and easily detectable fluorescent marker for video‐assisted thoracoscopic surgery (VATS). A bronchoscopic injection approach enables marking of multiple lesion areas without increasing the risk of pneumothorax.

SUMMARYDopa decarboxylase (DDC) regulates the synthesis of monoaminergic neurotransmitters and is linked to psychiatric and metabolic disorders. Ddc exhibits complex genomic imprinting effects that have not been functionally studied. Here, we investigate different noncanonical imprinting effects at the cellular level with a focus on Ddc. Using allele-specific reporter mice, we found Ddc exhibits dominant expression of the maternal allele in subpopulations of cells in 14 of 52 brain regions, and dominant paternal or maternal allele expression in adrenal cell subpopulations. Maternal versus paternal Ddc allele null mutations differentially affect offspring social, foraging and exploratory behaviors. Machine learning analyses of naturalistic foraging in Ddc−/+ and +/− offspring uncovered finite behavioral sequences controlled by the maternal versus paternal Ddc alleles. Additionally, parental Ddc genotype is revealed to affect behavior independent of offspring genotype. Thus, Ddc is a hub of maternal and paternal influence on behavior that mediates diverse imprinting and parental effects.HIGHLIGHTSDopa decarboxylase (Ddc) allelic expression resolved at the cellular levelCells differentially express maternal versus paternal Ddc allelesMaternal and paternal Ddc alleles control distinct behavioral sequencesParental Ddc genotype affects offspring independent of mutation transmissioneTOCAllelic reporter mice and machine learning analyses reveal dopa decarboxylase is affected by diverse imprinting and parental effects that shape finite behavioral sequences in sons and daughters.

The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine. We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed. Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up. PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.

A retrospective, population-based study.To identify factors affecting long-term mortality and medical resources use in disabled spinal cord injury (SCI) patients after syringomyelia diagnosis.A National Health Insurance Research Database containing 10,374 patients with SCI.Data recorded between 1997 and 2012 for 376 disabled SCI patients with syringomyelia and 376 characteristics-matched disabled SCI patients without syringomyelia were collected. The index date was the date of syringomyelia diagnosis. Cox proportional hazards regression model was used to investigate the factors affecting 10-year mortality in these patients. Medical resources use was compared for 1 year before and after index date.The survival rate at 10-year follow-up after syringomyelia diagnosis was estimated at 68.6%. The 10-year survival rate was comparable between the two groups. Age ≥ 60 (adjusted hazard ratios (aHR) 4.21, 95% confidence interval (CI) 2.97 to 5.96) and 30 years (aHR 0.25, 95% CI 0.10 to 0.62), spinal cord or spinal canal operations within 1 year after the index date (aHR 1.84, 95% CI 1.19 to 2.84), history of pneumonia (aHR 1.55, 95% CI 1.07 to 2.26), and history of coronary heart disease (CHD) (aHR 1.85, 95% CI 1.18 to 2.89) were significantly associated with long-term mortality. Outpatient prescription costs were higher during 1 year after the diagnosis than those of 1 year before the diagnosis.Age, spinal operations, history of pneumonia, and history of CHD are associated with 10-year mortality in disabled SCI patients with syringomyelia.

The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry, the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood&ndash, brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs.

MnAlNi powder was prepared by the process of vacuum levitation melting and high-energy ball milling, The morphology and phase structure of the powder were analyzed by Scanning Electron Microscope(SEM), X-ray diffraction(XRD) and the effect of the Ni content on microwave absorbing properties of MnAl powder was investigated by an vector network analyzer. The addition of Ni, which improved the microwave absorbing properties of MnAl powder but not changed the composition of Al 8 Mn 5 alloy. The minimum reflectivity of (Al 8 Mn 5 ) 0.95 Ni 0.05 powder with a coating thickness ( d ) of 1.8 mm was about −40.8 dB and has better bandwidth effect, the absorbing mechanism of AlMnNi powders on the electromagnetic was related to the electromagnetic loss within the absorbing coatings and the effect of coating thickness on the interference loss of electromagnetic wave.

The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

High-grade gliomas (HGGs) are a rapidly progressive and highly recurrent group of primary brain tumors. Despite aggressive surgical resection with chemoradiotherapy, prognoses remained poor. Valproic acid (VPA), a histone deacetylase inhibitor has shown the potential to inhibit glioma cell growth in vitro through several diverse mechanisms. However clinical studies regarding the effect of VPA on HGGs are limited. This study aimed to investigate whether using VPA in patients with HGGs under temozolomide (TMZ) would lead to a better overall survival (OS).We used the Taiwan National Health Insurance Research database to conduct this population-based cohort study. A total of 2379 patients with HGGs under TMZ treatment were included and were further classified into VPA (n = 1212, VPA ≥ 84 defined daily dose [DDD]) and non-VPA (n = 1167, VPA < 84 DDD) groups. Each patient was followed from 1998 to 2013 or until death. A Cox proportional hazard regression was performed to evaluate the effect of VPA and OS.The VPA group had a longer mean OS time compared with the non-VPA group (OS: 50.3 ± 41.0 vs 42.0 ± 37.2 months, P < .001). In patients between 18 and 40 years old, the difference is most significant (OS: 70.5 ± 48.7 vs 55.1 ± 46.0, P = .001). The adjusted hazard ratio is 0.81 (95% confidence interval, 0.72-0.91) for the VPA group relative to the non-VPA group.VPA at over 84 DDD improved OS in HGGs TMZ treatment.

The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine.We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed.Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up.PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.

SummaryHere, we describe an RNA-sequencing (RNA-seq)-based approach that accurately detects even modest maternal or paternal allele expression biases at the tissue level, which we call noncanonical genomic imprinting effects. We profile imprinting in the arcuate nucleus (ARN) and dorsal raphe nucleus of the female mouse brain as well as skeletal muscle (mesodermal) and liver (endodermal). Our study uncovers hundreds of noncanonical autosomal and X-linked imprinting effects. Noncanonical imprinting is highly tissue-specific and enriched in the ARN, but rare in the liver. These effects are reproducible across different genetic backgrounds and associated with allele-specific chromatin. Using in situ hybridization for nascent RNAs, we discover that autosomal noncanonical imprinted genes with a tissue-level allele bias exhibit allele-specific expression effects in subpopulations of neurons in the brain in vivo. We define noncanonical imprinted genes that regulate monoamine signaling and determine that these effects influence the impact of inherited mutations on offspring behavior.

The pre-reaction temperature effects on the crystallization and micro-structure of xonotlite for C–S–H gels with Ca/Si ratio = 1 using a steam assisted crystallization process was investigated. The pre-reaction temperature affected the crystallinity, pore structure and silicate chain structure of C–S–H gels, thereby influencing the xonotlite micro-structure and formation kinetics. A higher Q 2/Q 1 Si peak intensity ratio were observed in C–S–H gels pre-reacted at 80 °C, indicating that a higher pre-reaction temperature can promote condensation reactions between the Si–OH units, and hence transforming of silicate chain structure from a single chain structure to a double chain structure. The XRD background intensities around 2Θ = 20°–35° resulting from the occurrence of amorphous C–S–H phase decreased as the pre-reaction temperature increased, suggesting that the pre-reaction temperature can increase the degree of structural order and crystallinity. More xonotlite were formed for C–S–H gels pre-reacted at 40 °C and 60 °C after reacting at 180 °C for 32 h and 190 °C for 16 h compared to the sample pre-reacted at 80 °C, due to the decrease of the solubility resulting from the increase of the average silicate chain length and the decrease of Ca/Si ratio after pre-reaction at 80 °C.

Summary Interactions between genetic and epigenetic effects shape brain function, behavior, and the risk for mental illness. Random X inactivation and genomic imprinting are epigenetic allelic effects that are well known to influence genetic architecture and disease risk. Less is known about the nature, prevalence, and conservation of other potential epigenetic allelic effects in vivo in the mouse and primate brain. Here we devise genomics, in situ hybridization, and mouse genetics strategies to uncover diverse allelic effects in the brain that are not caused by imprinting or genetic variation. We found allelic effects that are developmental stage and cell type specific, that are prevalent in the neonatal brain, and that cause mosaics of monoallelic brain cells that differentially express wild-type and mutant alleles for heterozygous mutations. Finally, we show that diverse non-genetic allelic effects that impact mental illness risk genes exist in the macaque and human brain. Our findings have potential implications for mammalian brain genetics. Video Abstract

In this paper, three 5-GHz power amplifiers (PAs) are presented, which were implemented in 0.18- μm CMOS technology on different package substrates using flip-chip assembly. To make a fair comparison, the three PAs use the same circuit topology and transistor peripherals. The first case is a fully on-chip integrated CMOS PA with on-chip inductors. The second case uses low-temperature cofired ceramic (LTCC) inductors for the matching network, and the CMOS die is flip-chip-assembled on the LTCC substrate. For the last case, the CMOS bare die is assembled on the ceramic integrated passive device (CIPD) substrate, also by the flip-chip technique, and CIPD inductors are used as the matching network. Moreover, the PA performances with respect to the quality factor of inductors are discussed and verified with the experimental results. The fully on-chip integrated CMOS PA performs at 25.2 dB gain and 22.5 dBm OPSAT with a peak PAE of 22%. The system-in-package (SiP) CMOS PA on LTCC demonstrates 27 dB gain and 23.5 dBm OPSAT with a peak PAE of 27.5%, and the SiP CMOS PA on CIPD performs with 26.8 dB gain and 24 dBm of OPSAT with a peak PAE of 30%. With low-loss inductors on LTCC or CIPD, the maximum improvements of gain and PAE at PSAT can be up to 1.5 dB and 8 percentage Points, compared to the fully on-chip PA. To our knowledge, this is the first comprehensive PA performance comparison for different SiP approaches.

The pressure hull is a very important for the overall performance of underwater vehicles, this paper investigates the structural performance of cylindrical pressure hull for underwater vehicles. Taking into account that there are much factors affect the performance of pressure hull, and these factors exists some coupling relationship between each other for pressure hull performance, so the orthogonal design method has been used in this paper, which can establish the representative test program. The ultimate strength of pressure hull is calculated with the finite element method. A design of experiments is performed to evaluate the effect of geometry parameters to the ultimate strength of the pressure hull. Through this study, the designers can clearly understand the influence degree of geometry parameters for pressure hull performance, which can provide reference for the structural design of cylindrical pressure hull.

Introduction Perforator flap transfer has the benefits of minimal donor site morbidity and customization in design. This study reports on the proximal lateral leg perforator (PLLP) flap transfer for head and neck reconstruction. Materials and Methods From January 2000 through December 2009, 18 patients underwent head and neck reconstruction with the PLLP flap, including 16 males and 2 females ranging in age between 32 and 80 years old. The mean follow-up time was 9.8 months. Results Mother vessels of PLLP flaps can arise 77.8% (14/18) from the peroneal system, 11.1% (2/18) from the posterior tibial system, or 11.1% (2/18) from the common popliteal system. The skin dimension ranges from 4 cm × 7 cm to 6.5 cm × 18 cm. The mean of the perforator size is 1.96 mm (1.5 mm to 2.3 mm). The mean of the pedicle length is 6.96 cm (4.5 cm to 10 cm). All flaps survived completely except one flap that had partial necrosis. Conclusions The PLLP flap for head and neck reconstruction offers versatility in design, diverse tissues for composition, a two-team approach, and negligible donor site morbidity, and it spares major vessels. The unpredictable pedicle length and the feasibility for microvascular anastomosis in the perforator level can be adapted with further experience and refining techniques.

Background Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. Methods Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day −1 and 10) and 16 mg/kg cyclosporine (day 0–10) and were separated into groups 1, 2, 3, 4, and 5 according to the day −1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 10 6 T-cell–depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft- versus -host disease (GVHD) was assessed clinically and histologically. Results Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥20%, n = 15) than in low-chimerism ( n = 5) rats that accepted CTA long-term . Conclusions The chimerism level correlated positively with GVHD occurrence and long-term CTA acceptance but correlated negatively with regulatory T-cell levels. Optimal chimerism for CTA acceptance through pre-CTA BMT and irradiation occurs at 20–50% at day 28 after BMT in the rat model.

In this paper, the weak signal detection under α stable noise is investigated based on bistable vibrational resonance (VR) which is driven by a high frequency signal. On the one hand, the energy of the high frequency drive signal is transferred to the low frequency weak signal when VR occurs; on the other hand, the control of stochastic resonance (SR) is achieved based on VR, which transfers more noise energy into useful signal energy. In addition, considering the requirements of real-time detection, the amplitude and frequency of the high frequency drive signal are optimized by the knowledge-based particle swarm optimization (KPSO), which takes the mean signal-noise-ratio (MSNR) of output as the fitness function, and the property that VR system produces the best resonance effect just when the valid system parameter â(B,Ω) is greater than zero as knowledge. Finally, the parameter compensation is combined to achieve multi-high frequency weak signals detection with a stable noise. Furthermore, the method is applied to the vibration fault diagnosis of a mono-crystalline silicon furnace, and the experiment results show the effectiveness and practicability of the method.

Background. Mucosal or oral tolerance, an established method for inducing low-risk antigen-specific hyporesponsiveness, has not been investigated in vascularized composite allograft (VCA) research. We studied its effects on recipient immune responses and VCA rejection. Methods. Lewis rats (n = 12; TREATED) received seven daily intrajejunal treatments of 5 × 107 splenocytes from semiallogeneic Lewis-Brown-Norway rats (LBN) or vehicle (n = 11; SHAM). Recipients' immune responses were assessed by mixed lymphocyte reaction (MLR) against donor antigen and controls. Other Lewis (n = 8; TREATED/VCA) received LBN hindlimb VCA and daily intrajejunal treatments of 5 × 107 LBN splenocytes, or LBN VCA without treatment (n = 5; SHAM/VCA), until VCAs rejected. Recipients' immune responses were characterised and VCAs biopsied for histopathology. Immunosuppressants were not used. Results. LBN-specific hyporesponsiveness was induced only in treated Lewis recipients. Treatment significantly reduced MLR alloreactivity, significantly reduced VCA rejection on histopathology, and significantly delayed clinical VCA rejection (P < 0.0005; TREATED/VCA mean 9.6 versus 6.0 days for SHAM/VCA). Treatment significantly increased immunosuppressive IL-10/IL-4/TGF-β production and significantly decreased proinflammatory IFN-γ/TNF-α. Conclusion. Jejunal exposure to antigen conferred donor specific hyporesponsiveness that delayed VCA rejection. This method may offer a low-risk adjunctive treatment option to help protect VCAs from rejection.

chen m.-y., huang w.-c., peng y.-s., guo j.-s., chen c.-p., jong m.-c. & lin h.-c. (2011) Effectiveness of a health promotion programme for farmers and fishermen with type-2 diabetes in Taiwan. Journal of Advanced Nursing 67(9), 2060–2067. Abstract Aims. This paper is a report of a study examining the diabetes control and foot self-care capability in farmers and fishermen following introduction of a multi-stage, multi-disciplinary team and community-based small group health promotion programme. Background. Improving the control of diabetes is a critical issue in Taiwan because mortality rates are increasing dramatically, particularly in rural populations. Methods. A quasi-experimental research design was deployed from January to December 2009. A total of 387 participants living in nine rural districts with previous diagnoses of type-2 diabetes were randomly selected. Three hundred and twenty-three completed the 3-stage programme, including health assessment, health promotion education and individually tailored telephone counselling and evaluation over a 1-year period. Results. Most of the participants were fishermen or farmers who had

Background: The standardized mortality rate of type 2 diabetes is higher in Taiwan than that in other developed countries. In Taiwan, the diabetes mortality rate in Chiayi County is the highest nationwide. Purpose: This study was designed to explore the health status (to measure six physiological indicators), the health-related behaviors, and the associated factors among type 2 diabetes sufferers living in rural communities. Methods: Researchers used a cross-sectional, correlation design and conducted the study at nine local health districts in Chiayi County, Taiwan. A total of 387 participants previously diagnosed with type 2 diabetes were randomly selected and invited to join in the program. Results: Fifty-nine percent of participants were women; their mean age was 68.7 years, and their mean duration with diabetes was 7.9 years. Most were treated at local health centers and took oral medications (90.7%). More than 40% did not exercise regularly and 33.9% did not practice diet control. Results found a higher percentage of abnormal health indicators in terms of participant body mass index, waist circumference, HbA1C, and peripheral neurovascular function. After controlling for potential confounding factors, researchers found smaller waist circumference, participating in community support groups, better foot self-care capability, and frequent exercise to be associated with better health indicators. Diabetes duration, lower education, and being of male gender were found to be negatively associated with health status. Conclusions/Implications for Practice: This study found that rural residents with diabetes do not adequately control their diabetes and exhibit inadequate health-related behavior. Joining community support groups, increasing exercise frequencies, and improving foot self-care capabilities should be employed in nursing strategies and health policies for diabetes control-especially for those who have less formal education or are male.

BACKGROUND: Previous studies demonstrated that both cyclosporine and tacrolimus in combination with antilymphocyte globulin could facilitate mixed chimerism and induce tolerance to composite tissue allotransplants under partial myeloablative conditioning. The purpose of this study was to compare the efficacy of cyclosporine and tacrolimus. METHODS: Brown-Norway and Lewis rats were used as composite tissue allotransplant donors and recipients, respectively. Cyclosporine groups I (n = 6), II (n = 9), and III (n = 5) received subcutaneous injection of 16 mg/kg cyclosporine (days 0 to 10); intraperitoneal injection of 5 mg of antilymphocyte globulin (days -1 and 10); and 0-, 200-, and 400-cGy total body irradiation (day -1), respectively. Tacrolimus groups IV (n = 6), V (n = 7), and VI (n = 8) received intraperitoneal injection of 1 mg/kg tacrolimus (days 0 to 10) and 5 mg of antilymphocyte globulin (days -1 and 10); and 0-, 200-, and 400-cGy total body irradiation (day -1), respectively. Recipients underwent hind-limb osteomyocutaneous flap composite tissue allotransplantation on day 0. Chimerism levels were determined 2 weeks after composite tissue allotransplantation, and acceptance was defined as complete survival of the composite tissue allotransplant to the endpoint of the experiment at 150 days. RESULTS: Chimerism levels 2 weeks after composite tissue allotransplant averaged 3.4, 4.9, 29, 2.4, 4.9, and 16 percent composite tissue allotransplant, and acceptance rates were 0, 33.3, 80, 0, 0, and 13 percent in group I, II, III, IV, V, and VI, respectively. CONCLUSION: Despite relatively late development for clinical use in transplantation, tacrolimus has not proved advantageous for composite tissue allotransplant acceptance and tolerance when compared with cyclosporine.

Oral submucous fibrosis causes health-related and social problems for affected patients. Free flap reconstruction has proved effective for maintaining mouth opening after release of fibrosis. Two independent free flaps from separate donor sites, such as bilateral forearm flaps or bilateral anterolateral thigh (ALT) flaps, were traditionally required for reconstruction. The former option sacrifices one of the two major arteries in the forearm. Both options are time consuming and required two donor sites. To eliminate these disadvantages, we developed a technical modification that allows harvesting of two independent flaps from one ALT thigh based on one descending branch of the lateral circumflex femoral artery (d-LCFA). Eighteen flaps from nine donor sites were harvested for post-release reconstruction of oral submucous fibrosis. Mean flap size was 4.1 x 7.5 cm, mean pedicle length was 7.6 cm, mean ischaemia time was 104 min and mean total operation time was 13 h and 19 min. All donor sites were closed primarily, with one exception. One flap failed and was replaced with a contralateral ALT flap. One patient developed a wound infection and another developed a seroma at the recipient site. Four flaps required secondary de-bulking in three patients. The improvement in mouth opening was evaluated by inter-incisor distance (IID): mean preoperative IID was 9.6mm (range: 0-20mm), mean follow-up time was 16.2 months (range: 10-33 months); mean postoperative IID was 23.8mm and mean improvement in IID was 15.3mm (range: 10-27 mm). In conclusion, two independent flaps can be harvested from d-LCFA of the same thigh, instead of from both thighs, to reconstruct bilateral buccal defects after release of submucous fibrosis and/or contracture.

Background Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. Methods Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6) T-cell-depleted ACI (RT1A(abl)) bone marrow cells were transplanted on day 0, followed by a 11-day course of tacrolimus and one dose of antilymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4 to 6 weeks after bone marrow transplantation. Results Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-alphabeta-T-cell receptor (TCR) monoclonal antibody (mAb) (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-alphabeta-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving more than or equal to 300 cGy TBI plus anti-alphabeta-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap acceptors lost peripheral blood chimerism within 6 months. However, donor chimerism persisted in the transplanted bone at significantly higher levels compared with other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of peripheral blood chimerism. Conclusions Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.

Composite tissue allotransplantation (CTA) research faces two critical challenges. Firstly, the most applicable experimental model(s) in which CTA tolerance induction regimens should be characterized and tested requires clarification. Secondly, it has not been determined what would constitute a suitable endpoint for clinical trials of such methodologies before progression toward wider clinical application could be considered appropriate. Currently, the most reliable method to induce CTA tolerance in animals is to establish mixed hematopoietic chimerism using bone marrow transplantation (BMT) from an allogeneic donor. This approach has three important constraints: (i) the requirement for toxic myeloablative conditioning; (ii) a prerequisite 28-day delay period between BMT and CTA; and (iii) the potential for inducing graft-versus-host disease (GVHD). We review the history of chimerism induction for CTA, the strategies that have been proposed to circumvent CTA-related problems, and the insights that have been gained from our own research into these issues. The benefits of vascularized BMT (VBMT) over conventional BMT for inducing CTA tolerance are highlighted. The establishment of mixed chimerism and the induction of tolerance require further research and refinement before they can be applied clinically. A safe and robust method of tolerance induction encourages wider application of reconstructive CTA with fewer ethical obstacles.

Microsurgical free tissue transfer has become a reliable technique. Nevertheless, 5 to 25 percent of transferred flaps require re-exploration due to circulatory compromise. This study was conducted to evaluate the timing of occurrence of flap compromise following free tissue transfer, and its correlation with salvage outcome.Between January of 2002 and June of 2003, 1142 free flap procedures were performed and 113 flaps (9.9 percent) received re-exploration due to compromise. All patients were cared for in the microsurgical intensive care unit for 5 days. Through a retrospective review, timing of presentation of compromise was identified and correlated with salvage outcome.Seventy-two flaps (63.7 percent) were completely salvaged and 23 (20.4 percent) were partially salvaged. Eighteen flaps (15.9 percent) failed completely. Ninety-three flaps (82.3 percent) presented with circulatory compromise within 24 hours; 108 (95.6 percent) presented with circulatory compromise within 72 hours, and 92 flaps (85.2 percent) were salvaged within this period. One out of the three flaps presenting with compromise 1 week postoperatively was salvaged. Flaps presenting with compromise upon admission to the microsurgical intensive care unit had significantly lower complete salvage rates as compared with those without immediate abnormal signs (40.9 percent versus 69.2 percent, p = 0.01).The time of presentation of flap compromise is a significant predictor of flap salvage outcome. Intensive flap monitoring at a special microsurgical intensive care unit by well-trained nurses and surgeons allows for early detection of vascular compromise, which leads to better outcomes.

Composite tissue allotransplantation (CTA) is the new frontier in transplantation. More than 25 hand allograft transplants have been performed worldwide, and the feasibility has been well established. The classical experimental model of CTA involves rat orthotopic hindlimb transplantation, a time-consuming procedure associated with high mortality and morbidity. We describe a rat heterotopic osteomyocutaneous flap that serves as a nonfunctional CTA, allowing the study of tolerance induction to a highly antigenic vascularized allograft of bone, muscle, and skin while minimizing the morbidity and mortality of full hind limb transplantation. In the present studies, we explored whether establishing chimerism by nonmyeloablative conditioning would induce tolerance to CTA. When compared with the classic hind limb transplantation model, these results demonstrate that our heterotopic hind limb flap is less morbid and as an effective experimental model for the study of CTA tolerance.

Background The radial forearm flap has been a workhorse flap for soft-tissue or coverage reconstruction in the head and neck area. Although it has several major advantages, it requires sacrifice of the radial artery. In this article, the authors present their modification of harvesting a forearm flap based on a large septocutaneous branch of the radial artery in the proximal forearm with or without sacrificing the main radial artery. They name it the proximal radial forearm flap. Methods From September of 2003 to March of 2004, a total of 14 free proximal radial forearm flaps were used for head and neck reconstruction in 12 patients. There was one female patient and 11 male patients. Their ages ranged from 32 to 85 years. The skin flap size ranged from 2.0 x 6.0 cm to 4.5 x 18 cm. Results All free proximal radial forearm flap reconstructions had immediate success. There were one delayed flap loss caused by wound infection and one death attributable to advanced medical disease. Six flaps were harvested with preservation of the radial artery trunk. Six of the eight radial arteries that were killed during flap harvest were repaired with a short segment (3 to 4 cm) of vein graft. The average diameter and length of the septocutaneous vessel of the proximal radial forearm flap was 0.73 mm and 3.3 cm, respectively. Two flaps were harvested in conjunction with the conventional free radial forearm flaps. Nine donor sites were closed primarily and five donor sites required skin grafts. Conclusions The proximal radial forearm flap can be used successfully in head and neck reconstruction with the advantages of moving the donor site to the proximal forearm for better scar concealment and possible preservation of the radial artery trunk. The disadvantages of this flap are short pedicle length and small pedicle diameter when the radial artery is to be preserved.

Background Massive defects of the head and neck regions after resection of advanced carcinoma often require two flaps for optimal reconstruction. This study focuses on the selection of proper recipient vessels. Methods A total of 262 free-flap transfers were performed in 130 patients using the two-flap approach (one patient received two flaps twice). Results For microvascular anastomosis of inner flaps (intraoral lining-bone reconstruction flaps), the ipsilateral facial artery was used in 56 flaps (42.8 percent), the ipsilateral superior thyroid artery was used in 49 flaps (37.4 percent), and a branch of the internal jugular vein was used as recipient vein in 101 flaps (77.1 percent). For external flaps (soft-tissue-external skin reconstruction flaps), the ipsilateral superior thyroid artery was used in 59 flaps (50.4 percent) and the transverse cervical artery was used in 19 flaps (16.2 percent). In 14 patients the inner flaps provided distal run-off for external flap revascularization. Only seven flaps required vein grafts; they were all used for external face reconstruction (2.8 percent). There were six total (2.3 percent) and 12 partial (4.6 percent) flap failures. Conclusions Recipient vessel selection and preparation in primary head and neck cancer reconstruction requiring two simultaneous flaps should take into consideration (1) avoidance of unnecessary destruction during tumor ablations and preservation of as many neck vessels as possible, (2) length and diameter match between flap pedicles and recipient vessels to avoid vein grafts, and (3) possible need of another free-flap reconstruction for flap failure, complication, recurrence, or secondary primary cancers. The previously radiated or operated neck does not preclude the use of recipient vessels from that side. Distal run-off of the inner flap for external flap revascularization should be avoided if possible. Once those principles are observed, two-flap reconstruction for primary cancer presents no more difficulties than single-flap reconstruction.