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Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive superficial mesenchymal neoplasm characterized by monomorphic spindle‐cell proliferation with a storiform pattern. It can demonstrate pigmentation, myxoid changes, myoid differentiation, plaque‐like growth, and fibrosarcomatous features; its varied presentation often complicates diagnosis. We report an extremely rare case of fibrosarcomatous DFSP with features reminiscent of a pleomorphic hyalinizing angiectatic tumor (PHAT) in a 73‐year‐old male. The diagnosis was confirmed using a reverse transcription polymerase chain reaction. To the best of our knowledge, PHAT‐like changes in DFPS have not been described so far. Therefore, this report provides a novel variant of DFSP and expands the differential diagnosis of DFSP and PHAT. [ABSTRACT FROM AUTHOR]

The annual conference of the International Functional Electrical Stimulation Society (IFESS) was held in conjunction with the 7th RehabWeek Congress, from September 24 to 28, 2023 at the Resorts World Convention Centre on Sentosa Island, in Singapore. The Congress was a joint meeting of the International Consortium on Rehabilitation Technology (ICRT) together with 10 other societies in the field of assistive technology and rehabilitation engineering. The conference features comprehensive blend of technical and clinical context of FES, a sustained value the society has offered over many years. The cross‐ and inter‐ disciplinary approach of medicine, engineering, and science practiced in the FES community had enabled vibrant interaction, creation, and development of impactful and novel contributions to the field of FES, translating FES directly into highly relevant and sustainable solutions for the users. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to analyze the muscle magnetic resonance imaging (MRI) findings of patients with antineutrophilic cytoplasmic antibody‐associated vasculitis (AAV) and polyarteritis nodosa (PAN) presenting with clinical symptoms in the extremities. Methods: Retrospective analysis was conducted on short tau inversion recovery MRI findings, with a focus on intramuscular vessels displaying abnormal perivascular signals, in 22 and eight patients with AAV and PAN, respectively. The number per unit area (4 cm2) and diameter of abnormal vessels on muscle MRI were compared between patients with AAV and those with PAN. Cut‐off values, clinical sensitivity, and specificity for these indices were calculated from the receiver operating characteristic curves to distinguish between AAV and PAN, and the relationship between the indices and clinical findings in AAV was analyzed. Results: The number of abnormal vessels per unit area was significantly higher in AAV compared to PAN (p <.05). Additionally, the diameter of the abnormal vessels was significantly higher in PAN than in AAV (p <.05). The presence of >6.44 abnormal vessels per unit area or ≤3.61 mm diameter of abnormal vessels was able to predict AAV (sensitivity, 0.955; specificity, 0.625). AAV patients with peripheral neuropathy exhibited a significantly higher number of abnormal vessels per unit area than those without peripheral neuropathy (p <.05). Conclusions: Muscle MRI can detect small‐ to medium‐vessel vasculitis and be a valuable tool for distinguishing between patients with AAV and PAN experiencing clinical symptoms in the extremities. [ABSTRACT FROM AUTHOR]

The International Functional Electrical Stimulation Society (IFESS) held its annual meeting at the RehabWeek Conference in Rotterdam, Netherlands. The conference included workshops, keynote lectures, poster sessions, panel discussions, and parallel sessions covering various topics related to electrical stimulation. IFESS attracted researchers from around the world who presented on the development and applications of electrical stimulation. The field is expanding to include new applications and there is a growing interest in neuromodulation approaches for motor recovery. IFESS also awarded the Vodovnik Award to outstanding student contributions. The conference provided a valuable opportunity for cross-disciplinary collaboration and knowledge sharing. [Extracted from the article]

Background and Objective: The intrinsic electrical material properties of the laminar components of the mammalian peripheral nerve bundle are important parameters necessary for the accurate simulation of the electrical interaction between nerve fibers and neural interfaces. Improvements in the accuracy of these parameters improve the realism of the simulation and enables realistic screening of novel devices used for extracellular recording and stimulation of mammalian peripheral nerves. This work aims to characterize these properties for mammalian peripheral nerves to build upon the resistive parameter set established by Weerasuriya et al. in 1984 for amphibian somatic peripheral nerves (frog sciatic nerve) that is currently used ubiquitously in the in‐silico peripheral nerve modeling community. Methods: A custom designed characterization chamber was implemented and used to measure the radial and longitudinal impedance between 10 mHz and 50 kHz of freshly excised canine vagus nerves using four‐point impedance spectroscopy. The impedance spectra were parametrically fitted to an equivalent circuit model to decompose and estimate the components of the various laminae. Histological sections of the electrically characterized nerves were then made to quantify the geometry and laminae thicknesses of the perineurium and epineurium. These measured values were then used to calculate the estimated intrinsic electrical properties, resistivity and permittivity, from the decomposed resistances and reactances. Finally, the estimated intrinsic electrical properties were used in a finite element method (FEM) model of the nerve characterization setup to evaluate the realism of the model. Results: The geometric measurements were as follows: nerve bundle (1.6 ± 0.6 mm), major nerve fascicle diameter (1.3 ± 0.23 mm), and perineurium thickness (13.8 ± 2.1 μm). The longitudinal resistivity of the endoneurium was estimated to be 0.97 ± 0.05 Ωm. The relative permittivity and resistivity of the perineurium were estimated to be 2018 ± 391 and 3.75 kΩm ± 981 Ωm, respectively. The relative permittivity and resistivity of the epineurium were found to be 9.4 × 106 ± 8.2 × 106 and 55.0 ± 24.4 Ωm, respectively. The root mean squared (RMS) error of the experimentally obtained values when used in the equivalent circuit model to determine goodness of fit against the measured impedance spectra was found to be 13.0 ± 10.7 Ω, 2.4° ± 1.3°. The corner frequency of the perineurium and epineurium were found to be 2.6 ± 1.0 kHz and 368.5 ± 761.9 Hz, respectively. A comparison between the FEM model in‐silico impedance experiment against the ex‐vivo methods had a RMS error of 159.0 ± 95.4 Ω, 20.7° ± 9.8°. Conclusion: Although the resistive values measured in the mammalian nerve are similar to those of the amphibian model, the relative permittivity of the laminae bring new information about the reactance and the corner frequency (frequency at peak reactance) of the peripheral nerve. The measured and estimated corner frequency are well within the range of most bioelectric signals, and are important to take into account when modeling the nerve and neural interfaces. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic inflammatory myopathies (IIM) demonstrate characteristic clinical phenotypes depending on the myositis‐specific antibody (MSAs) present. We aimed to identify common or MSA‐specific immunological pathways in different immune cell types from peripheral blood by transcriptome analysis. Methods: We recruited 33 patients with IIM who were separated into the following groups: 15 patients with active disease at onset and 18 with inactive disease under treatment. All patients were positive for MSAs: anti–melanoma differentiation‐associated gene 5 (MDA5) antibody (Ab) in 10 patients, anti‐Mi‐2 Ab in 7, and anti‐aminoacyl‐transfer RNA synthetase (ARS) Ab in 16. The patients were compared with 33 healthy controls. Twenty‐four immune cell types sorted from peripheral blood were analyzed by flow cytometry, RNA sequencing, and differentially expressed gene analysis combined with pathway analysis. Results: The frequencies of memory B cell types were significantly decreased in active patients, and the frequency of plasmablasts was prominently increased in active patients with anti‐MDA5 Ab in comparison with healthy controls. The expression of type I interferon (IFN)‐stimulated genes of all immune cell types was increased in the active, but not inactive, patients. Endoplasmic reticulum stress‐related genes in all IIM memory B cells and oxidative phosphorylation‐related genes in inactive IIM double negative B cells were also increased, suggesting prominent B cell activation in IIM. Furthermore, active patients with anti‐MDA5 Ab, anti‐Mi‐2 Ab, or anti‐ARS Ab were distinguished by IFN‐stimulated and oxidative phosphorylation‐related gene expression in plasmablasts. Conclusion: Unique gene expression patterns in patients with IIM with different disease activity levels and MSA types suggest different pathophysiologies. Especially, B cells may contribute to common and MSA‐specific immunological pathways in IIM. [ABSTRACT FROM AUTHOR]

This article reports on a case of an aggressive undifferentiated small round cell sarcoma of the thorax that showed a fusion between the TOP2B and UBA3 genes. This type of sarcoma has not been reported previously. The patient, a 64-year-old woman, presented with back pain and was diagnosed with a malignant round cell tumor. Despite treatment with chemotherapy, the tumor continued to grow, and the patient eventually chose best supportive care. The article provides a detailed description of the tumor's characteristics and discusses the potential implications of the TOP2B::UBA3 fusion. [Extracted from the article]

Rapid and reliable identification of targetable driver mutations in patients with advanced stage lung cancer is essential. Adequate amount of tumor tissue biopsies (i.e., genomic biopsies) are required to successfully analyze the gene panel. In the present case, we performed three pleural fluid investigations, including transbronchial biopsy of the primary tumor, transesophageal endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) of lymph node metastasis, and thoracoscopic biopsy of the pleural seeding sites. Among the three investigations, thoracoscopic biopsy alone successfully obtained a sufficient amount of tissue. Thus, it is important to determine the technique and site of biopsy, as multiple biopsies are not only burdensome to the patient, but also lead to significant delays in therapy induction. [ABSTRACT FROM AUTHOR]

Background: The stimulation and recording performance of implanted neural interfaces are functions of the physical and electrical characteristics of the neural interface, its electrode material and structure. Therefore, rapid optimization of such characteristics is becoming critical in most clinical and research studies. This paper describes the development of an upgraded 3D printed cuff electrode shell design containing a novel intrinsically conductive polymer (ICP) for stimulation and recording of peripheral nerve fibers. Methods: A 3D stereolithography (SLA) printer was used to print a scalable, custom designed, C‐cuff electrode and I‐beam closure for accurate, rapid implementation. A novel contact consisting of a percolated carbon graphite base electrodeposited with an intrinsically conductive polymer (ICP), poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) produced a PEDOT:PSS + carbon black (CB) matrix that was used to form the electrochemical interface on the structure. Prototype device performance was tested both in‐vitro and in‐vivo for electrical chemical capacity, electrochemical interfacial impedance, surgical handling, and implantability. The in‐vivo work was performed on the sciatic nerve of 25 anesthetized Sprague Dawley rats to demonstrate recording and stimulating ability. Results: Prototypes of different spatial geometries and number of contacts (bipolar, tripolar, and tetrapolar) were designed. The design was successfully printed with inner diameters down to 500 μm. Standard bipolar and tripolar cuffs, with a 1.3 mm inner diameter (ID), 0.5 mm contact width, 1.0 mm pitch, and a 1.5 mm end distance were used for the functional tests. This geometry was appropriate for placement on the rat sciatic nerve and enabled in‐vivo testing in anesthetized rats. The contacts on the standard bipolar electrode had an area of 2.1 × 10−2 cm2. Cyclic voltammetry on ICP coated and uncoated graphite contacts showed that the ICP increased the average charge storage capacity (CSC) by a factor of 30. The corresponding impedance at 1 Hz was slightly above 1 kΩ, a 99.99% decrease from 100 kΩ in the uncoated state. The statistical comparison of the pre‐ versus post‐stimulation impedance measurements were not significantly different (p‐value > 0.05). Conclusions: The new cuff electrode enables rapid development of cost‐effective functional stimulation devices targeting nerve bundles less than 1.0 mm in diameter. This allows for recording and modulation of a low‐frequency current targeted within the peripheral nervous system. [ABSTRACT FROM AUTHOR]

Background: In‐silico experiments used to optimize and inform how peripheral nerve based electrode designs perform hold the promise of greatly reducing the guesswork with new designs as well as the number of animals used to identify and prove promising designs. Given adequate realism, in‐silico experiments offer the promise of identifying putative mechanisms that further inform exploration of novel stimulation and recording techniques and their interactions with bioelectric phenomena. However, despite using validated nerve fiber models, when applied to the more complex case of an implanted extracellular electrode, the in‐silico experiments often do not compare quantitatively with the results of experiments conducted in in‐vivo experiments. This suggests that the accuracy/realism of the environment and the lamination of the nerve bundle plays an important role in this discrepancy. This paper describes the sensitivity of in‐silico models to the electrical parameter estimates and volume conductor type used. Methods: In‐vivo work was performed on rat vagus nerves (N = 2) to characterize the strength‐duration curve for various peaks identified in a compound nerve action potential (CAP) measured via a needle electrode. The vagus nerve has several distinct populations of nerve fiber calibers and types. Recruitment of a fiber caliber/type generates distinct peaks that can be identified, and whose conduction delay correlates to a conduction velocity. Peaks were identified by their recruitment thresholds and associated to their conduction velocities by the conduction delays of their peaks. An in‐silico analog of the in‐vivo experiment was constructed and experiments were run at the two extreme volume conductor cases: (1) The nerve in‐saline, and (2) the nerve in‐air. The specifically targeted electrical parameters were extraneural environment (in‐air versus saline submersion), the resistivity (ρ) of the epineurium and perineurium, and the relative permittivity (εr) of those same tissues. A time varying finite element method (FEM) model of the potential distribution vs time was quantified and projected onto a modified McIntyre, Richardson, and Grill (MRG), myelinated spinal nerve, active fiber model in NEURON to identify the threshold of activation as a function of stimulus pulse amplitude versus pulse width versus fiber diameter. The in‐silico results were then compared to the in‐vivo results. Results: The finite element method simulations spanned two macro environments: in‐saline and in‐air. For these environments, the resistivities for low and high frequencies as well as two different permittivity cases were used. Between these 8 cases unique cases it was found that the most accurate combination of those variables was the in‐air environment for low‐frequency resistivity (ρ0) and ex‐vivo a measured permittivity (εr,measured) from unpublished ex‐vivo experiments in canine vagal nerve, achieving a high degree of convergence (r2 = 0.96). As the in‐vivo work was conducted in in‐air, the in‐air boundary condition test case was convergent with the in‐silico results. Conclusions: The results of this investigation suggest that increasing realism in simulations begets more accurate predictions. Of particular importance are (ρ) and extraneural environment, with reactive electrical parameters becoming important for input waveforms with energy in higher frequencies. [ABSTRACT FROM AUTHOR]

Background: The sinusoidal low‐frequency alternating current (LFAC) waveform was explored recently as a novel means to evoke nerve conduction block. In the present work, we explored whether increasing the amplitude of the LFAC waveform results in nerve fiber activation in autonomic nerves. In‐silico methods and preliminary work in somatic nerves indicated a potential frequency dependency on the threshold of activation. The Hering‐Breuer (HB) reflex was used as a biomarker to detect cervical vagus nerve activation. Methods: Experiments were conducted in isoflurane‐anesthetized swine (n = 5). Two stimulating bipolar cuff electrodes and a tripolar recording cuff electrode were implanted on the left vagus nerve. To ensure the electrical stimulation affects only the afferent pathways, the nerve was crushed caudal to the electrodes to eliminate cardiac effects. (1) Standard pulse stimulation (Vstim) using a monophasic train of pulses was applied through the caudal electrode to elicit HB reflex and to identify the activated nerve fiber type. (2) Continuous sinusoidal LFAC waveform with a frequency ranging from 5 through 20 Hz was applied to the rostral electrode without Vstim to explore the activation thresholds at each LFAC frequency. In both cases, the activation of nerve fibers was detected by a HB reflex‐induced reduction in the breathing rate. Results: LFAC was found to be capable of eliciting an HB response. The LFAC activation thresholds were found to be frequency‐dependent. The HB threshold was 1.02 ± 0.3 mAp at 5 Hz, 0.66 ± 0.3 mAp at 10 Hz, and 0.44 ± 0.2 mAp at 20 Hz. In comparison, it was 0.7 ± 0.47 mA for a 100 μs pulse. The LFAC amplitude was within the linear limits of the electrode interface. Damage to the cuff electrodes or the nerve tissues was not observed. Analysis of Vstim‐based compound nerve action potentials (CNAP) indicated that the decrease in breathing rate was found to be correlated with the activation of slower components of the CNAP suggesting that LFAC reached and elicited responses from these slower fibers associated with afferents projecting to the HB response. Conclusions: These results suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic nerve fibers and potentially provide a new modality to the neurorehabilitation field. [ABSTRACT FROM AUTHOR]

Ewing‐like adamantinoma (EAD) is a rare bone tumor. It remains unclear whether EAD belongs to adamantinoma, Ewing sarcoma (ES), or an independent category. Herein, we present a case of femoral sarcoma previously diagnosed as EAD in a 26‐year‐old woman. We observed amplified EWSR1 and NFATC2 fusion signals using fluorescence in situ hybridization. Prompted by its unique radiological features, we reviewed the current literature on skeletal EWSR1‐NFATC2 sarcoma (ENS) and EAD. In addition to the similar histological features, we found that both ENS and EAD displayed similar characteristic radiological features, such as the tendency to occur in the diaphysis of long bones, cortical expansion and buttressing‐type thickening, and bone surface involvement with saucer‐like erosion without cortical destruction. We believe that these unique radiological features were related to its indolent behavior. Altogether, it is possible that previously reported EAD cases may be neither ES nor the classic adamantinoma but ENS. Further studies are needed to clarify the relationship between EAD and ENS. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase (SDH)‐deficient renal cell carcinoma (RCC) is mainly associated with a mutation in the SDHB gene and sometimes with mutations in the SDHC or SDHD genes. However, only three cases of succinate dehydrogenase A (SDHA)‐deficient RCC have been reported, and the relation between SDHA mutations and RCC has not been clarified. This study assessed the role of SDHA gene mutations in human RCC. We investigated SDHA/B/C/D gene mutations in 129 human RCCs. Targeted next‐generation sequencing and direct Sanger sequencing revealed single nucleotide variants (SNVs) of the SDHA gene with amino acid sequence variations in 11/129 tumors, while no SDHB/C/D gene mutations were found. Tumor cells with SNVs of the SDHA gene were characterized by eosinophilic cytoplasm and various patterns of proliferation. Immunohistochemistry examination found that the 11 tumors with SNVs of the SDHA gene showed significant reduction of SDHA protein and SDHB protein expression compared to the 19 tumors without SDHA or SDHB mutations (both P <.0001). Western blotting showed a greater decrease in the expression of SDHA and SDHB proteins in the 11 tumors with SNVs of the SDHA gene than in the 19 tumors without (both P <.0001). There was a positive correlation between SDHA and SDHB protein levels (P <.0001). On immunohistochemistry and Western blotting, the 11 tumors with SNVs of the SDHA gene had higher protein expression for nuclear factor E2‐related factor 2 (Nrf2) compared to the 19 tumors without the mutation (P <.01). These observations suggest that SDHA gene mutations might be associated with a subset of RCC. [ABSTRACT FROM AUTHOR]

In the LV thrombi, eosinophil degranulation was not evident with hematoxylin-eosin staining, however, immunostaining revealed MBP labeling with intensities varied in each eosinophil (Figure 1d), reflecting different phases of eosinophil degranulation. (1) Infiltration of inflammatory cells including eosinophils induced endo-myocardial injury with elastic fiber disruption as well as mural thrombi, (2) LV mural thrombi caused multiple emboli in the small intramural coronary arteries with ischemic foci in the RV wall, (3) RV mural thrombus induced RV endo-myocardial ischemia through impaired uptake of luminal oxygen, (4) the aforementioned changes predisposed the thin RV posterior wall to rupture. Eosinophilic endomyocarditis (EEC) is caused by eosinophil infiltration.1 EEC is induced by multiple causes such as autoimmune diseases, parasitic infections, malignancies, drug hypersensitivity, and genetic aberrations.1,2 EEC with an unidentified cause, referred to as idiopathic hypereosinophilic syndrome (HES),1 frequently involves the heart2,3 and typically presents with congestive heart failure.1,3,4 Here we report the first case of an elderly male who suddenly died of cardiac tamponade due to right ventricle (RV) rupture in association with EEC. [Extracted from the article]

Aims/Introduction: The putative tumor suppressor gene, KBTBD11, might play a role in tumorigenesis, and is associated with cellular apoptosis and proliferation in colorectal cancer cells. However, the function of Kbtbd11 during adipogenesis is unknown. The aim of the present study was to investigate the role of Kbtbd11 in the differentiation of 3T3‐L1 preadipocytes. Materials and Methods: For the fasting–refeeding protocol, mice were subjected to fasting for 24 h, followed by a chow diet for 12 h. Adenovirus infection methods were used to examine the effect of Kbtbd11, and 3T3‐L1 cells were analyzed with Oil Red O staining and real‐time polymerase chain reaction. Results: The white adipose tissue expression of Kbtbd11 messenger ribonucleic acid (mRNA) was significantly higher in the re‐fed state than in the fasted state. Kbtbd11 mRNA levels were markedly increased in epididymal white adipose tissue of diet‐induced obesity mice compared with those in the mice fed a chow diet. In addition, Kbtbd11 mRNA expression was increased in a differentiation‐dependent manner in 3T3‐L1 cells. Knockdown of Kbtbd11 mRNA through the infection with adenoviral vectors remarkably inhibited triglyceride accumulation and adipocyte differentiation in 3T3‐L1 cells. In contrast, the overexpression of Kbtbd11 promoted the differentiation of 3T3‐L1 adipocytes. Conclusions: The present findings show that Kbtbd11 expression might be involved in nutritional regulation and is increased in obese adipose tissue. In addition, Kbtbd11 appears to be required for the differentiation of adipocytes in 3T3‐L1 cells. Collectively, these results show a novel link between the expression of Kbtbd11 and fat accumulation, and suggest that Kbtbd11 is a new therapeutic target for obesity. [ABSTRACT FROM AUTHOR]

Aim: Cancer‐associated fibroblasts (CAF) play a crucial role in angiogenesis in the complex tumor microenvironment. However, fibroblasts show extensive heterogeneity and their dynamic functions against stressors remain largely unknown. Methods: We collected patient‐derived CAF and carried out perturbation‐based monitoring of the dynamic functions. Clinically relevant experimental stimuli were defined as follows: hypoxia, cisplatin, fluorouracil, coculture with cancer spheroids (interaction through paracrine signals). We selected 18 marker genes that encode components for fibroblast activation, intracellular communication, and extracellular matrix remodeling. Quantitative reverse transcription polymerase chain reaction was carried out for data collection and statistical analyses were carried out using SPSS software. Results: Kruskal‐Wallis multivariate analysis of variance showed that variations in expression of 11 marker genes were explained, in part, by a difference in tissue of origin. Friedman and two‐sided Wilcoxon signed rank tests detected significant perturbations in expression of marker genes. Paracrine signal from cancer spheroids induced vascular endothelial growth factor A (VEGFA) in CAF but not in fetal lung fibroblasts. Conclusion: We have established perturbation‐based monitoring of patients' CAF. Further data collection and individual patient follow up is ongoing to identify critical determinants of disease outcome. [ABSTRACT FROM AUTHOR]

A rare case of a metastatic ectopic papillary thyroid carcinoma (PTC) of the lung that transformed into a squamous cell carcinoma (SCC) that resembles pulmonary SCC is reported. A subcutaneous ectopic PTC in the left anterior neck area, together with a normal thyroid gland, were excised. The ectopic PTC showed thyroglobulin, TTF‐1 and PAX‐8 immunoreactivity and a BRAF V600E mutation. During the post‐operative follow‐up period, a rapidly growing 2 cm nodular lesion in the lower left lobe of the lung was detected. The lung tumor consisted of solid sheets and nests of squamous cells but without the nuclear features of PTC. Neither papillary nor follicular structures of cancer cells were identified. Carcinoma cells were positive for TTF‐1, PAX‐8, p40, CK14, and p63, while showing a high Ki‐67 labeling index and a BRAF V600E mutation. These results support our interpretation of a PTC that originated from ectopic thyroid tissue in the left anterior neck and that developed a lung metastasis showing squamous cell differentiation. [ABSTRACT FROM AUTHOR]

Mitogen‐activated protein kinase (MAPK)‐interacting kinases 1 (Mnk1) and 2 (Mnk2) modulate translation initiation through the phosphorylation of eukaryotic translation initiation factor 4E, which promotes tumorigenesis. However, Mnk1 and Mnk2 are dispensable in normal cells, suggesting that the inhibition of Mnk1 and Mnk2 could be effective in cancer therapy. To provide a structural basis for Mnk1 inhibition, a novel Mnk1 inhibitor was discovered and the crystal structure of Mnk1 in complex with this inhibitor was determined. The crystal structure revealed that the inhibitor binds to the autoinhibited state of Mnk1, stabilizing the Mnk‐specific DFD motif in the DFD‐out conformation, thus preventing Mnk1 from switching to the active conformation and thereby inhibiting the kinase activity. These results provide a valuable platform for the structure‐guided design of Mnk1 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Only a few genetic variants have been reported in regulatory elements of blood group genes. Most of them affect GATA motifs, binding sites for the GATA-1 transcription factor.Study Design and Methods: Samples from two patients and one donor with unusual or discrepant serology for ABO, RhD, and RhCE antigens were analyzed by DNA sequencing. Analyzed regions included the coding sequence and portions of regulatory elements. The effect of some variants on gene expression was evaluated in reporter gene assays.Results: Three new alleles were identified. Their key variants are located in the ABO Intron 1 enhancer, the RHD proximal promoter, and the RHCE proximal promoter. IVS1 + 5859A was found in an African American patient with a group O forward type and a group B reverse type. 5'UTR-115C was the only RHD variant sequence found in a mixed-race black and Caucasian prenatal patient showing mixed-field agglutination with anti-D. 5'UTR-83T was found in several black donors and patients in the context of the genetically related RHCE*ceBI and RHCE*ceSM alleles. Reporter assays of promoter constructs including 5'UTR-115C or 5'UTR-83T showed a significant reduction in RH gene expression.Conclusion: Three new alleles in the ABO, RHD, and RHCE genes consist of single-nucleotide changes within GATA motifs, emphasizing the key role of GATA transcription factors in the expression of blood group genes. [ABSTRACT FROM AUTHOR]

To achieve this, IFESS is developing a number of initiatives including the IFESS webinar series, the IFESS patient perspective webinar series, the IFESS Clinician Map and the IFESS Next Generation Chapter. The International Functional Electrical Stimulation Society (IFESS) is a member-based, not-for-profit community and association whose stated mission is to promote the awareness, knowledge, and understanding of both electrical stimulation technologies and their uses. IFESS conference proceedings and the current IFESS special issue allow us to reach a multi-disciplinary audience of researchers engaged in cutting-edge technologies and advancing the clinical application of FES. [Extracted from the article]

BACKGROUND Aspergillus repens strain MK82 produces an aspartic protease (PepA_MK82) that efficiently decolorises red-pigmented proteins during dried bonito fermentation. However, further expansion of the industrial applications of PepA_MK82 requires the high-level production and efficient preparation of the recombinant enzyme. RESULTS The genomic DNA and cDNA fragments encoding the protease were cloned from strain MK82 and sequenced. Phylogenetic analysis of PepA_MK82 and comparisons with previously reported fungal aspartic proteases showed that PepA_MK 82 clusters with different groups of these enzymes. Heterologous expression of PepA_MK82 in Pichia pastoris yielded preparations of higher purity than obtained with an Escherichia coli expression system. Total protease activity in a 100- mL culture of the P. pastoris transformant was 14 times higher than that from an equivalent culture of A. repense MK82. The recombinant PepA_MK82 was easily obtained via acetone precipitation; the final recovery was 83%. PepA_MK82 and its recombinant had similar characteristics in terms of their optimal pH, thermostability, and decolorisation activity. The recombinant was also able to decolorise flaked, dried bonito and to bleach a blood-stained cloth. CONCLUSION Given its ability to hydrolyse and decolorise red-pigmented proteins, recombinant PepA_MK8 can be exploited in the food industry and as a stain-removal agent in laundry applications. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Objective We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM. Methods We prospectively evaluated 7 patients with DM and 7 patients with polymyositis (PM) for the detection of fasciitis with PDUS. MRI and PDUS were both performed in all patients. Fasciitis was histologically confirmed by en bloc biopsy. Results Among all patients with DM, 4 showed signs of fasciitis on MRI, while increased blood flow signals were observed along the fascia by PDUS in 6 DM patients, including 4 patients with early disease (<2 months after the onset of muscle symptoms). Histologically, significant fasciitis was confirmed in 4 patients with DM. In the remaining 3 patients with DM, significant fasciitis was not evident histologically, but mild proliferation of capillaries and mild inflammation were notable in the area of the fascia. Immunohistochemical staining for CD31 indicated abnormal neovascular proliferation in the fascia in patients with DM. None of the PM patients showed signs of fasciitis or increased vascularity by MRI, PDUS, or en bloc biopsy. Conclusion In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma ( RCC) is an immunogenic and proangiogenic cancer. Although antivascular endothelial growth factor ( VEGF) therapies achieve impressive responses in some patients, many tumors eventually develop resistance to such therapy. The B7 family molecules such as CTLA-4, PD-1, and PD-L1 are pivotal players in immune checkpoints that positively or negatively regulate various immune responses. Recently, immunotherapy based on blocking immune checkpoints with anti- CTLA4, anti- PD-1, or anti- PD-L1 antibodies has been proposed as a potential new approach to the treatment of metastatic RCC. Higher expression of PD-L1 and B7-H4 in the tumors is associated with a poor prognosis in RCCs, however, the clinical impact of serum levels of B7 family molecules has not been elucidated in patients with metastatic RCCs receiving VEGF-targeted agents. We assessed the preoperative serum levels of B7 family molecules, including CD80, CD86, PD-1, PD-L1, B7-H3, B7-H4, and CTLA-4, and CD28 in RCC patients, and determined their relations with various clinicopathological characteristics. Elevated preoperative serum levels of PD-L1 and B7-H4 were correlated with less differentiated tumors, higher invasive and metastatic potential, a worse response to anti- VEGF therapy, and shorter overall survival. These findings suggested that investigating preoperative serum levels of PD-L1 and B7-H4 might not only be useful to assess the biological aggressiveness of RCCs, but also to predict the efficacy of anti- VEGF therapy and the eventual prognosis, indicating the future design of clinical trials of therapies targeting immune checkpoint in advanced RCCs. [ABSTRACT FROM AUTHOR]

Key points Intramuscular electrodes developed over the past 80 years can record the concurrent activity of only a few motor units active during a muscle contraction., We designed, produced and tested a novel multi-channel intramuscular wire electrode that allows in vivo concurrent recordings of a substantially greater number of motor units than with conventional methods., The electrode has been extensively tested in deep and superficial human muscles., The performed tests indicate the applicability of the proposed technology in a variety of conditions., The electrode represents an important novel technology that opens new avenues in the study of the neural control of muscles in humans., Abstract We describe the design, fabrication and testing of a novel multi-channel thin-film electrode for detection of the output of motoneurones in vivo and in humans, through muscle signals. The structure includes a linear array of 16 detection sites that can sample intramuscular electromyographic activity from the entire muscle cross-section. The structure was tested in two superficial muscles (the abductor digiti minimi (ADM) and the tibialis anterior (TA)) and a deep muscle (the genioglossus (GG)) during contractions at various forces. Moreover, surface electromyogram (EMG) signals were concurrently detected from the TA muscle with a grid of 64 electrodes. Surface and intramuscular signals were decomposed into the constituent motor unit (MU) action potential trains. With the intramuscular electrode, up to 31 MUs were identified from the ADM muscle during an isometric contraction at 15% of the maximal force (MVC) and 50 MUs were identified for a 30% MVC contraction of TA. The new electrode detects different sources from a surface EMG system, as only one MU spike train was found to be common in the decomposition of the intramuscular and surface signals acquired from the TA. The system also allowed access to the GG muscle, which cannot be analysed with surface EMG, with successful identification of MU activity. With respect to classic detection systems, the presented thin-film structure enables recording from large populations of active MUs of deep and superficial muscles and thus can provide a faithful representation of the neural drive sent to a muscle. [ABSTRACT FROM AUTHOR]

A total synthesis of prunustatin A, a GRP78 molecular chaperone down-regulator, has been achieved. The key step in the synthesis is an intramolecular transesterification of the β-keto ester alcohol intermediate to construct the 15-membered tetralactone core of the natural product. [ABSTRACT FROM AUTHOR]

Two amylases, amylase I and amylase II from Bacillus subtilis strain FP-133, were purified to homogeneity and characterized. Their stabilities toward temperature, pH, and organic solvents, and their substrate specificities toward polysaccharides and oligosaccharides were similar. Under moderately high salt conditions, both amylases were more stable than commercial B. licheniformis amylase, and amylase I retained higher amylase activity than amylase II. The N-terminal amino acid sequence, genomic southern blot analysis, and MALDI-TOFF-MS analysis indicated that the halotolerant amylase I was produced by limited carboxy-terminal truncation of the amylase II peptide. The deduced amino acid sequence of amylase II was >95% identical to that of previously reported B. subtilis α-amylases, but their carboxy-terminal truncation points differed. Three recombinant amylases - full-length amylase corresponding to amylase II, an artificially truncated amylase corresponding to amylase I, and an amylase with a larger artificial C-terminal truncation - were expressed in B. subtilis. The artificially truncated recombinant amylases had the same high amylase activity as amylase I under moderately high salt conditions. Sequence comparisons indicated that an increased ratio of Asp/Glu residues in the enzyme may be one factor responsible for increasing halotolerance. [ABSTRACT FROM AUTHOR]

This work evaluated the subchronic stimulation performance of an intraneural multichannel electrode (transverse intrafascicular multichannel electrode, TIME) in a large human-sized nerve. One or two TIMEs were implanted in the right median nerve above the elbow joint in four pigs for a period of 32 to 37 days (six TIMEs in total). The ability of the contact sites to recruit five muscles in the forelimb was assessed via their evoked electromyographic responses. Based on these responses, a selectivity index was defined. Four TIMEs were able to selectively recruit a subset of muscles throughout the implantation period. The required recruitment current significantly increased, while there was a tendency for the recruitment selectivity to decrease over time. Histological assessment showed that all TIMEs remained inside the nerve and that they were located between fascicles. The average thickness of the encapsulation of the electrode was estimated to be 115.4 ± 51.5 μm (mean ± SD). This study demonstrates the feasibility of keeping the TIME electrodes fixed and functional inside a large polyfascicular human-sized nerve in a subchronic setting. [ABSTRACT FROM AUTHOR]

Objective To examine whether the citrullinated chemokines epithelial neutrophil-activating peptide 78 (ENA-78)/CXCL5, macrophage inflammatory protein 1α/CCL3, and monocyte chemotactic protein 1/CCL2 are detected in the biologic fluid of patients with rheumatoid arthritis (RA), and if so, to determine the biologic activities of these chemokines. Methods Recombinant human chemokines were citrullinated by peptidylarginine deiminase. Enzyme-linked immunosorbent assays were performed to measure the concentrations of citrullinated chemokines in sera from patients with rheumatoid arthritis (RA) and normal individuals and in synovial fluid from patients with RA, patients with osteoarthritis (OA), and patients with other inflammatory rheumatic diseases. The correlation between the citrullinated chemokine levels and clinical data was analyzed. Monocyte and neutrophil chemotaxis assays were performed, and native (noncitrullinated) or citrullinated ENA-78/CXCL5 was injected into mouse knees to evaluate the biologic activities of these chemokines. Results The concentration of citrullinated ENA-78/CXCL5 was significantly higher in RA sera and SF than in normal sera and in SF from patients with other rheumatic diseases including OA. In RA SF, a strong correlation between the amount of citrullinated ENA-78/CXCL5 and the C-reactive protein level or the erythrocyte sedimentation rate was observed. Citrullinated ENA-78/CXCL5 induced monocyte chemotaxis via CXCR1 and CXCR2, while noncitrullinated ENA-78/CXCL5 did not. In a mouse model of inflammatory arthritis, citrullinated ENA-78/CXCL5 induced more severe inflammation and recruited more monocytes than did noncitrullinated ENA-78/CXCL5. Conclusion Citrullinated ENA-78/CXCL5 is highly correlated with RA disease activity and, unlike noncitrullinated ENA-78/CXCL5, recruits monocytes. These results indicate that citrullinated ENA-78/CXCL5 may exert previously unrecognized inflammatory properties in RA by recruiting monocytes to inflamed joint tissue. [ABSTRACT FROM AUTHOR]

Aim: Autophagy has been implicated in lipid droplet (LD) turnover. Adipose differentiation-related protein (ADRP) and microtubule-associated protein 1 light chain 3 (LC3) monitor LD and autophagosomes, respectively. We examined whether immunohistochemical staining of ADRP and LC3 can monitor LD and autophagy, and if so, whether autophagy is related to LD turnover in post-mortem human livers. Methods: We performed conventional immunohistochemistry of LC3 in paraffin-embedded human livers with different severities of steatosis, obtained at autopsy. Double immunofluorescence microscopy using anti-LC3 and anti-ADRP antibodies was performed to elucidate the relationship between autophagy and LD turnover. Results: LC3 immunohistochemistry reproducibly delineated puncta in normal human livers, which were preferentially located around the central venal zone. The extent of LC3 immunostaining reduced with progressing steatosis. Double immunofluorescence for ADRP and LC3 demonstrated an inverse relationship between ADRP positive areas and LC3 positive areas, as well as the co-localization of ADRP and LC3 on a part of small LD but not large LD. Conclusion: These findings suggest that impaired autophagy promotes steatosis and that autophagy may be implicated in LD turnover. [ABSTRACT FROM AUTHOR]

A case study of a 43-year-old woman, was admitted to our hospital with a 5-month history of myalgia in both calves and thighs. Topics include laboratory investigations revealed a C-reactive protein level of a normal creatine kinase level, and negative results for antinuclear antibodies; and antineutrophil cytoplasmic antibodies against myeloperoxidase and proteinase rheumatoid factor, and anti-cyclic citrullinated peptide antibodies.

Aim The purpose of the present study was to identify molecular markers of hepatic damage during lipopolysaccharide ( LPS) treatment. Methods LPS (15 mg/kg of bodyweight) or vehicle was injected i.p. into 5-week-old male Sprague- Dawley rats. Proteins were extracted from the liver and were electrophoresed to examine the changes in the protein compositions during LPS treatment. Using a proteomic approach, major LPS-responsible protein in the liver was determined. Results A massive reduction in the levels of carbamoyl phosphate synthase-1 ( CPS1), one of the most abundant proteins in liver mitochondria, was revealed during LPS administration. Electron microscopic and immunofluorescence analyses revealed large vacuoles, which were often localized in the vicinity of mitochondria, in the LPS-treated rat liver. Furthermore, we found that CPS1 is released into the circulation prior to liver damage marker alanine aminotransferase, indicating the active extrusion of CPS1 during LPS administration. Another liver mitochondrial protein, ornithine transcarbamylase, is also released into the circulation, implicating active extrusion of mitochondrial proteins. These phenomena are accelerated by a heme oxygenase inducer cobalt protoporphyrin whilst suppressed by a lysosome inhibitor chloroquine. Conclusion Plasma CPS1 should be a possible marker of septic liver damage and may be involved in systemic responses elicited by septic shock. [ABSTRACT FROM AUTHOR]

Aim: Mitochondrial damage and subsequent oxidative stresses play important roles in the pathogenesis of sepsis-induced organ failure. Recently, autophagy, the major degradation pathway involved in mitochondrial quality control, was reported as a cellular adaptive response to oxidative stresses. The aim of the present study was to elucidate the molecular mechanism that underlies hepatic damage during lipopolysaccharide (LPS) treatment. We also try to determine if the damage can be attenuated by administration of cobalt protoporphyrin (CoPP), a potent heme oxygenase-1 (HO-1) inducer. Methods: Five-week-old male Sprague-Dawley rats were injected i.p. with 15 mg/kg LPS. To determine if hepatic damage following LPS administration can be attenuated by HO-1, CoPP was injected s.c. for 4 days consecutively at 24-h intervals. After treatment with LPS, the liver was obtained and analyzed. Results: A large reduction in liver mitochondrial protein and induction of autophagy were observed in LPS-treated rats. Electron microscopic and immunohistochemical analyses demonstrated autophagic vacuoles in LPS-treated rat liver. Oxidative stress markers (4-hydroxy-2-nonenal and 8-hydroxy-2′-deoxyguanosine) were increased in LPS-treated animals; CoPP treatment ablated these alterations. An inhibitor for the opening of mitochondrial permeability transition pore, cyclosporine A, suppressed oxidative stress as well as liver damage during LPS administration. CoPP promoted autophagy and prevented rats from liver damage during LPS administration. Conclusion: HO-1 promotes autophagy and elimination of damaged mitochondria thereby repressing oxidative stress in LPS-treated rat liver, revealing a novel mechanism for protection by HO-1 against septic liver damage. [ABSTRACT FROM AUTHOR]

The article presents information on a study which determined whether fasciitis is histopathologically identifiable in patients with dermatomyositis (DM) and the process of inflammatory progression in myopathy accompanying DM. A review of the related literature on DM is presented. Methods utilized include en bloc biopsy combined with magnetic resonance imaging (MRI), immunohistochemical staining and statistical analysis. A discussion on the findings is detailed.

To evaluate the efficacy of extended-release (ER) tolterodine 4 mg/day for the treatment of neurogenic detrusor overactivity (NDO) and/or low-compliance bladder by assessing urodynamic parameters. Forty-six patients (25 male, 21 female; mean age 57.6 ± 20.7 years) with NDO ( n = 39) and/or low-compliance bladder ( n = 7) were included in this 12-week single-arm study. Twenty-one patients (46%) were on clean intermittent catheterization and other patients could void on their own. A video urodynamic study was performed before and at 3 months after treatment. Changes in Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and King's Health Questionnaire (KHQ) as well as changes in number of voids, amount of each void, and number of leaks in 24 h according to the 3-day voiding diary were also evaluated before treatment and at weeks 4 and 12 after treatment. Bladder capacity at first sensation and maximum cystometric capacity increased significantly, by an average of 36.8 mL ( P = 0.0402) and 82.3 mL ( P < 0.0001), respectively. Maximum cystometric capacity increased by more than 50 mL in 19 patients (49%) following treatment. Detrusor overactivity disappeared in three of 32 patients (9%), bladder capacity at first involuntary contraction increased significantly ( P = 0.0009), and amplitude of detrusor overactivity decreased significantly ( P = 0.0025). In patients with low-compliance bladder, bladder compliance increased significantly ( P = 0.0156). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire-Short Form score, number of voids (per 24 h and night-time), number of urgency episodes in 24 h, number and amount of leaks in 24 h, and amount of mean and maximum voided volumes all decreased significantly after treatment. Tolterodine is effective and well tolerated for the treatment of NDO and/or low-compliance bladder in patients with neurogenic bladder. [ABSTRACT FROM AUTHOR]

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To investigate the influence of the revised Gleason grading system (GGS, revised at a consensus conference organized by the International Society of Urological Pathology in 2005) on prediction of prognosis for patients with prostate cancer with bone metastasis. PATIENTS AND METHODS Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS), modified global GGS (MGGGS), and modified highest GGS (MHGGS). The patients were divided into two groups (Gleason score ≤7 and ≥8) using each grading system. Prostate-specific antigen failure-free survival after hormone therapy (HT) was estimated retrospectively. The Cox proportional hazard method was used for univariate and multivariate analysis. RESULTS Patients with a Gleason score of ≤7 had a significantly longer remission than patients with a score of ≥8 according to each GGS. However, the better prognosis patients were detected more precisely by the CGGS and MGGGS than the MHGGS. Multivariate analysis showed that the CGGS and MGGGS were significant prognostic indicators for the outcome of HT after adjustment for other prognostic factors. CONCLUSIONS These results suggest that the CGGS and MGGGS are more useful than the MHGGS as prognostic indicators for HT. Further evaluation in larger series is needed to define its clinical usefulness. [ABSTRACT FROM AUTHOR]

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Purpose: To evaluate the diagnostic ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCEI) in combination with T2-weighted imaging (T2WI) for the detection of prostate cancer using 3 T magnetic resonance imaging (MRI) with a phased-array body coil. Materials and Methods: Fifty-three patients with elevated serum levels of prostate-specific antigen (PSA) were evaluated by T2WI, DWI, and DCEI prior to needle biopsy. The obtained data from T2WI alone (protocol A), a combination of T2WI and DWI (protocol B), a combination T2WI and DCEI (protocol C), and a combination of T2WI plus DWI and DCEI (protocol D) were subjected to receiver operating characteristic (ROC) curve analysis. Results: The sensitivity, specificity, accuracy, and area under the ROC curve (Az) for region-based analysis were: 61%, 91%, 84%, and 0.8415, respectively, in protocol A; 76%, 94%, 90%, and 0.8931, respectively, in protocol B; 77%, 93%, 89%, and 0.8655, respectively, in protocol C; and 81%, 96%, 92%, and 0.8968, respectively in protocol D. ROC analysis revealed significant differences between protocols A and B ( P = 0.0008) and between protocols A and D ( P = 0.0004). Conclusion: In patients with elevated PSA levels the combination of T2WI, DWI, DCEI using 3 T MRI may be a reasonable approach for the detection of prostate cancer. J. Magn. Reson. Imaging 2010;31:625-631. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. Methods: Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3–10 µM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. Results: In detrusor without urothelium, maximum contraction (Emax) decreased after administration of fasudil at 3 or 10 µmol/L (both P < 0.01), or 30 µmol/L (72.5 ± 7.43%, 58.4 ± 8.04% and 68.4 ± 9.6%, respectively, of the first curve). In detrusor with urothelium, Emax decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 µmol/L of fasudil (84.9 ± 6.7%, 67.9 ± 5.2% and 35.2 ± 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 µmol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 µmol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 µmol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1–50 Hz decreased significantly in a concentration-dependent manner after addition of fasudil (3 to 30 µmol/L). Conclusions: Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways. [ABSTRACT FROM AUTHOR]

We examined the suppressive effects of estradiol on psychological stress–induced cardiovascular responses and oxidative stress in ovariectomized rats, both placebo-treated (OVX+Pla) and estrogen-treated (OVX+E2). The elevations in blood pressure and heart rate induced by cage-switch stress were attenuated in the OVX+E2 as compared with the OVX+Pla group. NG-nitro-L-arginine methyl ester, administered via drinking water, reduced the difference in these responses. Furthermore, this stress increased plasma nitrotyrosine and decreased plasma nitric oxide (NO) metabolites only in the OVX+Pla group. We demonstrated that estrogen replacement suppresses cardiovascular responses to psychological stress, at least in part by improving NO bioavailability in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Neuromodulation has been reported to be effective for the treatment of stress and urgency urinary incontinence. The cure and improvement rates of pelvic floor neuromodulation in urinary incontinence are 30–50% and 60–90%, respectively. In clinical practice, vaginal, anal and surface electrodes are used for external, short-term stimulation, and sacral nerve stimulation for internal, chronic (long-term) stimulation. The effectiveness of neuromodulation has been verified in a randomized, placebo-controlled study. However, the superiority to other conservative treatments, such as pelvic floor muscle training has not been confirmed. A long-term effect has also been reported. In conclusion, pelvic floor exercise with adjunctive neuromodulation is the mainstay of conservative management for the treatment of stress incontinence. For urgency and mixed stress plus urgency incontinence, neuromodulation may therefore be the treatment of choice as an alternative to drug therapy. [ABSTRACT FROM AUTHOR]

The Ran small GTPase (Ran) is involved in the regulation of nuclear transport, microtubule nucleation and dynamics, and spindle assembly. To address the question of whether Ran protein is associated with the progression of renal cell carcinoma (RCC), we compared by Western blotting the Ran protein levels in surgical RCC specimens from 180 consecutive Japanese patients with those in the corresponding nontumor tissue from the same patient. We also examined the Ran protein levels in tumors of different grades and stages. Ran proteins were more abundant in RCC tumor tissues than in nontumor tissues ( p < 0.0001). High Ran expression was associated with higher grade, local invasion, and metastasis ( p < 0.0001). Kaplan-Meier plots linked high Ran protein expression to a shorter overall survival in all cases ( p < 0.0001) and a shorter disease-free survival in those without metastasis at radical or partial nephrectomy (M0; 131 cases, p < 0.0001). Ran protein expression was an independent factor influencing overall survival univariate analysis ( p < 0.0001) and disease-free survival by multivariate analysis ( p < 0.05). Our findings suggest that Ran is associated with the progression of RCC. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aim: Androgen-deprivation therapy for prostate cancer decreases bone mineral density and increases the risk of fracture. The effect of risedronate, a potent third-generation oral bisphosphonate, on bone loss during androgen deprivation therapy was investigated. Methods: Sixty-one prostate cancer patients with a mean age (±SD) of 79 ± 6 years who had received androgen deprivation therapy for 42 ± 29 months were enrolled, and were treated with 2.5 mg of risedronate daily for six months. Bone mineral density was measured at the femoral neck, lumbar spine, and ultradistal radius by dual energy X-ray absorptiometry. The percent change of bone mineral density after treatment with risedronate was calculated as the primary efficacy variable. Urinary N-telopeptide of type I collagen was measured as a bone resorption marker. Results: Bone mineral density remained stable in the femoral neck and radius during risedronate therapy. In contrast, the bone mineral density of the lumbar spine showed a significant increase from 1069 ± 488 mg/cm2−1112 ± 497 mg/cm2 ( P < 0.001), representing a gain of 4.9 ± 8.9%. Urinary N-telopeptide of type I collagen decreased significantly ( P < 0.001) after three months of risedronate treatment. Conclusions: Risedronate could prevent and reverse bone loss in men receiving androgen deprivation therapy for prostate cancer by inhibiting bone resorption. [ABSTRACT FROM AUTHOR]

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo-radiotherapy. Evaluation of XRCC1 gene polymorphism as a biomarker in head and neck cancer patients undergoing chemoradiation therapy. Objective assessment of dermatitis following post-operative radiotherapy in patients with breast cancer treated with breast-conserving treatment. [Extracted from the article]

Abstract: The measurement of the biomechanical properties of gastrointestinal smooth muscle cells is important for the basic understanding of digestive function and the interaction of muscle cells with the matrix. Externally applied forces will deform the cells depending upon their mechanical properties. Hence, the evoked response mediated through stretch-sensitive ion-channels in the smooth muscle cell membrane will depend upon membrane properties and the magnitude of the external force. The aim of this study was to test the hypothesis that gastrointestinal smooth muscle cells behave in a viscoelastic manner. Smooth muscle cells were dissociated from the muscle layers of the descending colon. The viscoelastic properties of the isolated cells were characterized by measuring the mechanical deflection response of the cell membrane to a negative pressure of 1cm H2O applied across the cell through a micropipette and fitting the response to a theoretical viscoelastic solid model. The viscoelastic mechanical constants of the isolated cells (N =9) were found to be as follows: k 1 =19.99±2.86Pa, k 2 =7.19±1.21Pa, μ =25.36±6.14Pas and τ =4.84±0.95s. This study represents, to the best of our knowledge, the first quantitative mechanical properties of isolated living smooth muscle cells from the gastrointestinal tract. The mechanical properties determined in this study will be of use in future analytical and numerical smooth muscle cell models to better predict the mechanism between the magnitude of mechanical stimuli, mechanosensitivity and the evoked afferent responses. [Copyright &y& Elsevier]

Many bacterial genomes encode multiple metal-sensing ArsR-SmtB transcriptional repressors. There is interest in understanding and predicting their metal specificities. Here we analyse two arsR-smtB genes, ydeT and yozA (now aseR and czrA) from Bacillus subtilis. Purified AseR and CzrA formed complexes in gel-retardation and fluorescence-anisotropy assays with fragments of promoters that were derepressed in Δ aseR and Δ czrA cells. Candidate (i) partly thiolate, α3-helix (for AseR) and (ii) tetrahedral, non-thiolate, α5-helix (for CzrA) metal binding sites were predicted then tested in vitro and/or in vivo. The precedents are for such sites to sense arsenite/antimonite (α3) and zinc (α5). This correlated with the respective metal inducers of AseR and CzrA repressed promoters in B. subtilis and matched the metals that impaired formation of protein–DNA complexes in vitro. The putative sensory sites of 1024 ArsR-SmtB homologues are reported. Although AseR did not sense zinc in vivo, it bound zinc in vitro exploiting α3 thiols, but AseR DNA binding was not impaired by zinc. If selectivity relies on discriminatory triggering of allostery not just selective metal binding, then tight non-effector metal complexes could theoretically inhibit metal sensing. AseR remained arsenite-sensitive in equimolar zinc, while CzrA remained zinc-sensitive in equimolar arsenite in vitro. However, cupric ions did not impair CzrA–DNA complex formation but did inhibit zinc-mediated allostery in vitro and prevent zinc binding. Access to copper must be controlled in vivo to avoid formation of cupric CzrA. [ABSTRACT FROM AUTHOR]