Insufficient Suppression Research Articles

Frequency-specific disruptions of neuronal oscillations reveal aberrant auditory processing in schizophrenia.

Individuals with schizophrenia exhibit abnormalities in evoked brain responses in oddball paradigms. These could result from (a) insufficient salience-related cortical signaling (P300), (b) insufficient suppression of irrelevant aspects of the auditory environment, or (c) excessive neural noise. We tested whether disruption of ongoing auditory steady-state responses at predetermined frequencies informed which of these issues contribute to auditory stimulus relevance processing abnormalities in schizophrenia. Magnetoencephalography data were collected for 15 schizophrenia and 15 healthy subjects during an auditory oddball paradigm (25% targets; 1-s interstimulus interval). Auditory stimuli (pure tones: 1 kHz standards, 2 kHz targets) were administered during four continuous background (auditory steady-state) stimulation conditions: (1) no stimulation, (2) 24 Hz, (3) 40 Hz, and (4) 88 Hz. The modulation of the auditory steady-state response (aSSR) and the evoked responses to the transient stimuli were quantified and compared across groups. In comparison to healthy participants, the schizophrenia group showed greater disruption of the ongoing aSSR by targets regardless of steady-state frequency, and reduced amplitude of both M100 and M300 event-related field components. During the no-stimulation condition, schizophrenia patients showed accentuation of left hemisphere 40 Hz response to both standard and target stimuli, indicating an effort to enhance local stimulus processing. Together, these findings suggest abnormalities in auditory stimulus relevance processing in schizophrenia patients stem from insufficient amplification of salient stimuli.

Targeted vessel reconstruction in non-contrast-enhanced steady-state free precession angiography.

Image quality in non-contrast-enhanced (NCE) angiograms is often limited by scan time constraints. An effective solution is to undersample angiographic acquisitions and to recover vessel images with penalized reconstructions. However, conventional methods leverage penalty terms with uniform spatial weighting, which typically yield insufficient suppression of aliasing interference and suboptimal blood/background contrast. Here we propose a two-stage strategy where a tractographic segmentation is employed to auto-extract vasculature maps from undersampled data. These maps are then used to incur spatially adaptive sparsity penalties on vascular and background regions. In vivo steady-state free precession angiograms were acquired in the hand, lower leg and foot. Compared with regular non-adaptive compressed sensing (CS) reconstructions (CSlow ), the proposed strategy improves blood/background contrast by 71.3 ± 28.9% in the hand (mean ± s.d. across acceleration factors 1-8), 30.6 ± 11.3% in the lower leg and 28.1 ± 7.0% in the foot (signed-rank test, P < 0.05 at each acceleration). The proposed targeted reconstruction can relax trade-offs between image contrast, resolution and scan efficiency without compromising vessel depiction.

Stem cell therapy in animal models of allergic airway diseases

Allergic airway diseases are characterized by T-helper type 2 (Th2)-skewed eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness. The excessive activation of Th2 cells due to insufficient suppression of regulatory T cells (Tregs) is thought to play a major role in the initiation and development of allergic airway disease. Several studies have shown that stem cells provide a significant reduction in allergic airway inflammation and improve lung function in animal models. The immunomodula tory effects of stem cells in allergic airway disease may be mediated by the up-regulation of Tregs and increases in several soluble factors, such as prostaglandin E2, transforming growth factor-β, interleukin-10, and indoleamine 2, 3-dioxygenase. This review examines the current understanding of the immunomodulatory properties of stem cells and its therapeutic implication in allergic airway disease. Furthermore, we will discuss mechanisms by which stem cells inhibit allergic airway inflammation via immunomodula tion from a Th2- to a Th1-biased response. (Allergy Asthma Respir Dis 2016;4:167-173)

Mechanisms of diabetic autoimmunity: II--Is diabetes a central or peripheral disorder of effector and regulatory cells?

Two competing hypotheses aiming to explain the onset of autoimmune reactions are discussed in the context of genetic and environmental predisposition to type 1 diabetes (T1D). The first hypothesis has evolved along characterization of the mechanisms of self-discrimination and attributes diabetic autoimmunity to escape of reactive T cells from central regulation in the thymus. The second considers frequent occurrence of autoimmune reactions within the immune homunculus, which are adequately suppressed by regulatory T cells originating from the thymus, and occasionally, insufficient suppression results in autoimmunity. Besides thymic dysfunction, deregulation of both effector and suppressor cells can in fact result from homeostatic aberrations at the peripheral level during initial stages of evolution of adaptive immunity. Pathogenic cells sensitized in the islets are efficiently expanded in the target tissue and pancreatic lymph nodes of lymphopenic neonates. In parallel, the same mechanisms of peripheral sensitization contribute to tolerization through education of naïve/effector T cells and expansion of regulatory T cells. Experimental evidence presented for each individual mechanism implies that T1D may result from a primary effector or suppressor immune abnormality. Disturbed self-tolerance leading to T1D may well result from peripheral deregulation of innate and adaptive immunity, with variable contribution of central thymic dysfunction.

Insights into Catheter Ablation of Ventricular Tachycardias in Arrhythmogenic Right Ventricular Cardiomyopathy / Dysplasia

Arrhythmogenic right ventricular cardiomyopathy/ dysplasia (ARVC/D), mostly affecting young/middle-aged individuals, poses a significant risk of malignant ventricular arrhythmias (VAs) and subsequent sudden cardiac death (SCD). Antiarrhythmic agents (AAA) provide insufficient arrhythmia suppression and prevention and can be proarrhythmic. Thus, the implantable cardioverters-defibrillator (ICD) is considered the first-line treatment, especially in patients with secondary prevention indication. Nevertheless, catheter ablation is an additional therapy to the ICD which has proved its efficacy in primary and secondary prevention of fatal arrhythmias and sudden cardiac death. The superiority of the combined endo- and epicardial VT ablation in this population is clear since the ARVC/D substrate has been shown to be mostly epicardial. Due to progressive nature of ARVC/D, ablation seems to be a useful tool for the patients who experience recurrent VT episodes or electrical storms.

Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine, adefovir, and entecavir.

In the past decade, many chronic hepatitis B (CHB) patients have undergone sequential treatment with lamivudine (LAM), adefovir (ADV), and entecavir (ETV) to manage antiviral resistance or insufficient suppression of HBV-DNA. Very limited data are available on the efficacy of tenofovir (TDF) rescue regimens in patients with multidrug resistance (MDR). We investigated the antiviral efficacy of TDF/LAM combination therapy versus TDF/ETV combination therapy in 52 patients who failed three previous antiviral therapies. The study subjects were treated with TDF/LAM combination therapy (n = 25) or TDF/ETV combination therapy (n = 27) for more than six months. Virologic response (VR) occurred in 39 (75%) patients (19 patients belonged to the TDF/LAM group and 20 patients belonged to the TDF/ETV group). The VR rates were not different between the TDF/LAM and TDF/ETV groups (56.0% vs 51.9% at month 12, and 72.0% vs 78.8% at month 18; log rank P = 0.515). In addition, treatment efficacy of TDF/LAM combination or TDF/ETV combination was not statistically different according to types of MDR. In multivariate analysis, absolute HBV-DNA level at the start of TDF rescue treatment (P < 0.001; OR, 0.452; 95% CI, 0.306-0.666) was only significantly associated with VR. TDF/ETV combination therapy was not associated with higher rate of VR compared with TDF/LAM combination therapy in MDR CHB patients. These results raise the suspicion about the superiority of the combination therapy over TDF monotherapy. The lower HBV-DNA levels at the start of TDF-based rescue therapy were associated with higher VR.

PP.32.12

Objective: With the pandemic of obesity the identification of individuals with hypercortisolism gets more difficult. We analyzed the performance of the 1 mg dexamethasone suppression test (DST) in patients with obesity in a clinical setting. Design and method: We conducted a prospective cohort study in patients with obesity (MOS, NCT00770276). Patients presented in our outpatient department for metabolic and cardiovascular evaluation. After obtaining medical history patients were analysed for anthropometry, metabolism, and cardiovascular risk factors. For evaluation of hypercortisolism we performed a 1 mg dexamethasone-suppression test (DST) in all subjects as screening. In case of insufficient suppression of cortisol (>50nmol/l) further diagnostic assessment was performed: repeat DST, salivary midnight cortisol (SMC) and/or 24 h urine free cortisol (UFC). Medication was assessed for drugs with possibly interfering effects on DST and hypothalamic-pituitary-adrenal axis (e.g. CYP3A4 inducers, estrogen therapy, antidepressants and opiates). Results: A total of 278 patients with a mean age of 42.3years with a female predominance (68.8% women) were screened by DST. Anthropometrical data revealed a mean BMI of 47.9 ± 8.4 kg/m2 and a waist circumference of 137 ± 17.6 cm representing truncal obesity. Insufficient suppression of cortisol after DST was found in 24 patients (8.6%). In 2 patients hypercortisolism was confirmed by UFC. The specificity for DST was calculated with 92.0%. 45.0% of the cohort received confounding medication. Only CYP 3A4 inducers (n = 22, 7.9%) and estrogen therapy (n = 17, 6.1%) were significantly associated with pathological DST. After elimination of all patients with interfering medication specificity slightly increased to 94.9%. Regression analysis revealed no interrelation between DST and anthropometry. Conclusions: In obese patients presenting for bariatric therapy in a tertiary care center we found low prevalence of hypercortisolism (0.7 or < 1.8%). Specificity of DST in this cohort typically screened for hypercortisolism was 92.0% (<51nmol/l), which represents adequate performance. After elimination of interfering medication (CYP3A4 inducers and estrogen therapy) specificity increased only slightly. Furthermore, regression-analysis revealed no association with anthropometrical data, even though we studied patients with extreme measures. In summary DST is an adequate test for screening for hypercortisolism in a real clinical setting.

Developments towards detection of 135Cs at VERA

Radioisotopes produced in natural or anthropogenic fission are widely used for tracer studies of environmental processes, in nuclear forensics, and are important for nuclear waste disposal. Besides the well-known 137Cs, the longer-lived sister isotope 135Cs (T1/2=2.3Myr) is also produced, and the combined measurement of the two isotopes would allow for assessment of contaminating sources. The insufficient suppression of the stable isobar 135Ba presently prevents AMS measurements down to expected natural levels of 135Cs/133Cs≈10−11. Via the difference in electron affinities between Cs and Ba further isobar suppression should be achievable after the installation of the Ion-Laser-Interaction System (ILIAS) at VERA. We present a preparatory study on the performance of the 3MV VERA AMS facility for 135Cs concerning ion formation, transmission and detection. Since the usual Cs sputtering would obscure the 135Cs/133Cs ratio of a sample, Rb sputtering was successfully applied and tested also for various other typical AMS elements. Partial suppression of 135Ba is possible with the extraction of Cs− and negative Cs-fluorides. Cs− currents of several 10nA were extracted over hours from mg amounts of Cs2SO4 material. The transmission to various charge states was tested with gas (Ar, He) and foil stripping. Experiments showed that no suppression in the detection system is possible at high beam energies with the VERA facility. For this reason, gas stripping to low charge states (2+, 3+) with transmissions up to 30% is favorable to guarantee optimal beam transport to the detector. In the present setup, utilizing a simple Bragg-type detector, the blank 135Cs/133Cs ratios from chemically pure samples are determined by the 135Ba background to a value of (4.0±1.3)·10−9.

Improved 2D slice-interleaved flow-independent cardiac black blood imaging using Ferumoxytol

Background Double inversion recovery (DIR) is the most commonly used black blood (BB) preparation method. However its single slice nature makes the acquisition inefficient and flow-dependence causes insufficient blood suppression when stagnant blood or in-plane blood flow is present. In this work, we propose to use ferumoxytol, an FDA approved iron oxide particle for treating iron deficiency anemia, as an MR contrast agent to achieve flow-independent BB imaging by taking advantage of its strong

Lamivudine resistance in children with chronic hepatitis B.

Currently, although lamivudine (LAM) has a low genetic barrier, only interferon-alpha and LAM are available as a first-line treatment in children with chronic hepatitis B (CHB). LAM is a potent inhibitor of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) polymerase replication by termination of the proviral HBV-DNA chain. LAM has a good safety and tolerability profile in CHB patients with hepatic decompensation. However, the main disadvantages of this HBV reverse transcriptase inhibitor are: (1) pre-existing covalently closed circular DNA cannot be eradicated by LAM, thus relapse after therapy withdrawal is frequent; and (2) although the longer LAM treatment induced the higher seroconversion rate, the risk of viral resistance increased through the selection of YMDD (tyrosine, methionine, aspartate, aspartate) motif. Insufficient suppression of viral replication leads to the emergence of resistant strains that could result in virological breakthrough which is usually followed by biochemical breakthrough. Mutant strains affects additional resistance and cross resistance, leading to drug resistance in a significant number of CHB patients. In this case, efficacy of more powerful anti-viral agents with higher genetic barrier against development of resistance is diminished. Furthermore, strains that are resistant to LAM could bring about vaccine escape mutants, decreasing the efficacy of HBV vaccine. A more potent drug with a high genetic barrier to resistance needs to be approved as the first-line treatment option for CHB in children.

Insulin action in muscle and adipose tissue in type 2 diabetes: The significance of blood flow.

Under normal metabolic conditions insulin stimulates microvascular perfusion (capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physical exercise. This helps the delivery of insulin itself but also that of substrates and of other signalling molecules to multiple tissues beds and facilitates glucose disposal and lipid kinetics. This effect is impaired in insulin resistance and type 2 diabetes early in the development of metabolic dysregulation and reflects early-onset endothelial dysfunction. Failure of insulin to increase muscle and adipose tissue blood flow results in decreased glucose handling. In fat depots, a blunted postprandial blood flow response will result in an insufficient suppression of lipolysis and an increased spill over of fatty acids in the circulation, leading to a more pronounced insulin resistant state in skeletal muscle. This defect in blood flow response is apparent even in the prediabetic state, implying that it is a facet of insulin resistance and exists long before overt hyperglycaemia develops. The following review intends to summarize the contribution of blood flow impairment to the development of the atherogenic dysglycemia and dyslipidaemia.

Ezh2 Is Required for Developmental Stage-Specific Silencing of Oncofetal Genes in Hematopoietic Stem/Progenitor Cells

In contrast to adult bone marrow (BM) hematopoiesis, fetal liver (FL) hematopoiesis involves mainly erythropoiesis and myelopoiesis, with limited lymphopoiesis. Fetal hematopoietic stem cells (HSCs) are known to have greater repopulating capacity as compared with adult HSCs. Polycomb group (PcG) protein Ezh2 participates in gene silencing by catalyzing the trimethylation on H3K27 (H3K27me3). We previously reported that in transplantation assays, Ezh2-deficient FL hematopoietic cells have greater reconstitution capacity and establish significantly higher ratios of myeloid to lymphoid reconstitution relative to wild-type (WT). From these results, we hypothesized that adult BM hematopoietic cells repopulated with Ezh2-deficient FL cells partially retain the features of fetal hematopoietic cells as compared with WT.To address this hypothesis, we transplanted Cre-ERT;Ezh2fl/fl or WT FL hematopoietic cells and deleted Ezh2 (Ezh2 KO) via intraperitoneal administration of tamoxifen at 4 weeks after transplantation. At 3 months post-deletion of Ezh2, donor-derived lin-Sca-1+c-Kit+ (LSK) HSC/MPP fraction were recovered and subjected to microarray analysis, together with LSK cells from WT E15.5 FL and adult BM. Within genes which showed higher expression in Ezh2 KO BM LSK cells compared with WT (453 genes: Ezh2 KO-gene), and higher in FL compared with adult BM LSK cells (1139 genes: FL-gene), 102 genes (23% of Ezh2 KO-gene and 9% of FL-specific gene) were overlapped (p-value < 1.0x10-16).Recently, Copley et al. (Nat Cell Biol, 2013) revealed that Lin28b is exclusively expressed in FL HSCs and the Lin28b/let7/Hmga2 axis plays a critical role in controlling developmental changes in HSC properties. As reported, we found that Lin28b was detected only in FL LSK cells, but of note, remarkably higher expression was observed in Ezh2 KO relative to WT LSK cells in adult BM. Lin28b is known to block the maturation of let-7 microRNAs, thereby up-regulates expression of let-7 target genes. Within 1648 putative let-7 miRNA target genes, 136 genes were highly expressed in FL LSK cells (FL-LSK let-7 target). Gene set enrichment analysis (GSEA) showed that FL-LSK let-7 target gene set was ectopically enriched in Ezh2 KO LSK and also GMP cells but not in WT cells in adult BM.We next performed ChIP-seq analysis to evaluate the direct target of Ezh2 in adult BM, Lin28b promoter region appeared to be marked with PcG histone marks H3K27me3 and H2AK119Ub1 but not in FL. The levels of PcG histone marks were significantly low in Ezh2-deficient BM LSK cells and GMPs relative to WT. These findings indicate that Lin28 is directly regulated by PcG histone modifications in adult BM. Interestingly, Within FL-LSK let-7 target, 16 genes underwent H3K27me3 histone modifications in adult BM and several of them escaped gene silencing in the absence of Ezh2, including Igf2bp3, Hmga2, Jam3, Dcbld1 and Zfp354a., in the same way as Lin28b. These results demonstrated that a part of let-7 target genes are negatively regulated in BM not only by let-7 but also by PcG histone modifications in adult BM.Recent analyses have revealed that inactivating somatic mutations in epigenetic regulator genes such as EZH2 or TET2 occur frequently in patients with myelodysplastic disorders. We previously reported that Ezh2 is largely dispensable for adult HSCs in contrast to fetal hematopoiesis but after a long latency, deletion of Ezh2 in adult hematopoietic cells induces myelodysplastic/myeloproliferative neoplasm (MDS/MPN)-like disorders characterized by myelodysplasia with higher repopulating capacity of HSCs. Furthermore, concurrent depletion of Ezh2 and Tet2 markedly accelerated the development of myelodysplastic syndrome (MDS) and MDS/MPN. Lin28b and its targets Igf2bp1 and Igf2bp3 are characterized as ‘oncofetal’ genes, which is highly expressed not only in early embryogenesis but also in various tumors. Corresponding to these findings, FL-LSK let-7 target genes were highly and more significantly enriched in Tet2KD/KDEzh2Δ/Δ(DKO) LSK and GMPs from MDS or MDS/MPN mice relative to Ezh2 KO in adult BM.Taken together, Ezh2 is indispensable for the developmental stage-specific regulation of the Lin28b-let7 pathway, and Ezh2 deletion results in insufficient suppression of a subset of the oncofetal genes, which may contribute to the FL-like characteristics and the development of hematopoietic disorders. DisclosuresNo relevant conflicts of interest to declare.

The effects of anodal stimulation of the left prefrontal cortex on sentence production.

Most studies in which Anodal Transcranial Direct Current Stimulation (A-tDCS) has been used to improve language production have focused on single words. Yet sentence production requires more than lexical retrieval. For example, successful suppression of the past and careful planning of the future are two critical requirements for producing a correct sentence. Can A-tDCS improves those, and by extension, production at the sentence level? Given that many aspects of sentence production beyond word retrieval require frontally-mediated operations, we hypothesized that A-tDCS to the left prefrontal cortex should benefit various operation involved in producing sentences, two of which, suppression of the past and planning of the future, were targeted in this study. We used a paradigm that elicited construction of sentences through event description, but was structured enough to allow for between-subject comparison, clear error identification, and implementation of experimental manipulations to probe certain aspects of production. We showed that A-tDCS to the left PFC reliably decreased the number of incomplete and errorful sentences. When the origin of this improvement was probed, we found that A-tDCS significantly decreased errors due to premature commitment to the future word (insufficient internal monitoring), and had a marginal effect on errors of perseverations (insufficient suppression of the past). We conclude that A-tDCS is a promising tool for improving production at the sentence level, and that improvement can be expected when internal monitoring and control over verbal responses is impaired, or for certain cases of perseveratory errors.

Speckle suppression via sparse representation for wide-field imaging through turbid media.

Speckle suppression is one of the most important tasks in the image transmission through turbid media. Insufficient speckle suppression requires an additional procedure such as temporal ensemble averaging over multiple exposures. In this paper, we consider the image recovery process based on the so-called transmission matrix (TM) of turbid media for the image transmission through the media. We show that the speckle left unremoved in the TM-based image recovery can be suppressed effectively via sparse representation (SR). SR is a relatively new signal reconstruction framework which works well even for ill-conditioned problems. This is the first study to show the benefit of using the SR as compared to the phase conjugation (PC) a de facto standard method to date for TM-based imaging through turbid media including a live cell through tissue slice.

Natural killer T cells mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice (IRM7P.478)

Abstract Active vitamin D (1,25(OH)2D3) completely blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying vitamin D’s anti-inflammatory properties are not fully understood. In the present study, we have employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of natural killer T (NKT) cells in vitamin D-mediated protection from EAE. WT mice or mice deficient in all NKT cells (CD1d-/-) or invariant NKT (iNKT) cells (Jα18-/-) were fed control or 1,25(OH)2D3 (50 ng/day) supplemented diets. All mice fed control diet developed severe EAE. 1,25(OH)2D3treatment protected WT mice, but not CD1d-/- or Jα18-/- mice, from developing EAE. Development and severity of EAE were associated with insufficient suppression of the MOG-specific IL-17 response by 1,25(OH)2D3 treatment in CD1d-/- mice compared to WT mice. Activation of iNKT cells with α-galactosylceramide (α-GalCer) or 1,25(OH)2D3 treatment did not protect IL-4-/- mice from developing EAE. Furthermore, 1,25(OH)2D3 treatment of splenocytes in vitro resulted in decreased α-GalCer-induced IL-17 and increased IL-4 production. These studies demonstrate that NKT cells are important mediators of vitamin D-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection.

재밍 환경에서 잡음 부공간을 이용한 고속 모노펄스 방법

재밍 환경에서의 maximum likelihood(ML) 기반의 모노펄스 기법은 공분산 행렬의 역행렬을 이용하여 재머 신호를 억제시킨다. 재머 억제를 위해서는 재머 성분에 대한 충분한 횟수의 스냅샷(snapshot)이 필요하며, 높은 PRF 환경에서는 이것이 가능하지 않아 실시간 추적에 한계가 있다. 또한, JNR(Jammer to Noise Ratio)이 낮은 경우에는 재머의 스냅샷 수가 충분하더라도 정확한 재머 억제가 이루어지지 않아, 표적 방향 추정의 정확도가 감소한다. 본 논문에서는 재밍 환경에서 스냅샷이 적은 경우에도 ML 기반의 모노펄스 성능이 우수한 방법을 제안한다. 제안된 방법은 공분산 행렬의 잡음 부공간을 이용하는 모노펄스 방법으로, 이의 유도 과정을 보이고, 모의실험을 통해 기존의 방법에 비해 성능이 개선된 것을 보인다. A monopulse based on maximum likelihood(ML) in jamming scenario can suppress jamming signal using an inverse matrix of a covariance matrix. In order to achieve adequate suppression of jamming signal, the sufficient number of snapshots is required. However, this is not possible in high PRF scenario, which hinders a real-time tracking. Moreover, even with the large number of snapshots, the estimation accuracy of the target direction is decreased in low JNR(Jammer to Noise Ratio) due to insufficient jammer suppression. In this paper, we propose a monopulse algorithm that doesn't degrade performance significantly with a small number of snapshots and in low JNR. We show its derivation that exploits noise-jammer subspace of a covariance matrix, along with its performance through simulation.

The paediatric neuropathic bladder

Paediatric neuropathic bladder dysfunction can cause irreversible renal damage and urinary incontinence. Aetiologically, this condition is usually caused by a congenital neural tube defect. The majority of affected children can be successfully managed with the standard medical treatment of clean intermittent catheterisation and anticholinergic medication (typically oxybutynin). A small subset of patients who receive oral oxybutynin experience severe side-effects or insufficient suppression of detrusor overactivity. This group may require alternative medical or surgical management.

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

To evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS). In this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone-CRH (Dex-CRH) test was performed in 54 patients. FIFTY-THREE PATIENTS WERE DIAGNOSED WITH CD AND SUBSEQUENTLY TREATED. TWENTY PATIENTS WERE CLASSIFIED AS HAVING PSC. SERUM CORTISOL CIRCADIAN RHYTHM: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of >0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration >243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level >9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex-CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level >87 nmol/l (T=15 min) resulted in a PPV of 100% and an NPV of 90%. The Dex-CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.

Ultrasound image anisotropic diffusion de-speckling method based on Mallat-Zhong discrete wavelet transform wavelet

In view of speckle noise in ultrasound image, there are some disadvantages of traditional anisotropic diffusion methods, such as in-sufficient noise suppression and edge details preservation. A de-speckling method based on Mallat-Zhong Discrete Wavelet Transform( MZ-DWT) wavelet was proposed. The method used MZ-DWT wavelet and Expectation Maximization( EM) algorithm as the discrimination factor between homogeneous and edge regions, making it more accurately to control diffusion intensity and rate and achieving the noise suppression and details preservation. The experimental results show that, the proposed algorithm can better de-speckle while preserving image details and the performance of the method is better than the traditional anisotropic diffusion methods.

Partial Virological Response to Adefovir Add-On Lamivudine Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

Background/Aims: In patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB) receiving adefovir (ADV) add-on LAM therapy, insufficient viral suppression or the appearance of additional ADV resistance has remained unresolved. This study determined the partial virological response (PVR) criteria to predict a virological response (VR) at week 96 in these patients. Methods: 96 patients with LAM-resistant CHB (ADV add-on LAM therapy >2 years) were analyzed. For predicting VR at week 96, the area under the receiver operating characteristic curve values at different time points were compared to establish the optimal time point, and the maximal Youden index was calculated to determine the optimal cut-off hepatitis B virus (HBV) DNA level. Results: 50 (52.1%) patients achieved VR at 2 years after ADV add-on LAM therapy. The optimal PVR criteria were determined to be HBV DNA 500 IU/ml at week 48. 44 (45.8%) patients who met optimal PVR criteria showed a significantly higher risk for detectable HBV DNA levels at week 96 than those with a favorable VR (HBV DNA <500 IU/ml) at week 48. Conclusions: This study suggested optimal PVR criteria in patients with LAM-resistant CHB receiving ADV add-on LAM therapy. Modification of the antiviral agent regimen should be considered if the serum HBV DNA level exceeds 500 IU/ml at week 48.