IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of immunodeficiency virus infection in Ugandan infants.
The value of HIV-1 IgA antibodies for early diagnosis of HIV infection in infants in serum, saliva and urine was investigated at Mulago Hospital, Kampala. Sensitivity and specificity in serum of HIV-infected infants at different ages were: 0 to 1 months, 88 and 95%; 1 to 3 months, 88 and 97%; 4 to 6 months, 80 and 96%. They decreased between 67 and 77% and 80 to 91%, respectively, in older age groups. Sensitivity for saliva was lower (53 to 79%) and urine only 37 to 62%, although specificity was reasonably high (>85%). The high proportion of infants with raised HIV IgA in the first months of life (88%) may represent prenatal infection. Sensitivity of serum and especially salivary and urinary HIV IgA is too low to be of practical value for early diagnosis of HIV infection in infants.


Traceability of marketable Japanese shoro in New Zealand: using multiplex PCR to exploit phylogeographic variation among taxa in the Rhizopogon subgenus Roseoli.
Rhizopogon roseolus Corda (synonym Rhizopogon rubescens Tul.), an economically important edible mushroom associated with the Pinaceae (mostly Pinus sp.), has a global distribution resulting from the introduction of exotic trees into the Southern Hemisphere for plantation forestry. However, the marketability of R. roseolus varies with the place of origin. R. roseolus strains cultivated in New Zealand from local carpophores for the Japanese market are morphologically and biologically distinct from those produced in Japan and are consequently considered less valuable. In this study, the ITS1-5.8S-ITS2 rRNA (internal transcribed spacer [ITS]) region was used to examine the phylogenetic relationships of R. roseolus and other closely related fungi belonging to Rhizopogon subgenus Roseoli to determine the genetic basis for phenotypic differences among R. roseolus isolates from different geographic regions. Phylogenetic comparison revealed phylogeographic variation within Rhizopogon subgenus Roseoli. Collections from the United States and Europe grouped into four distinct clades. Rhizopogon roseolus isolates found in New Zealand were closely related to those from the United States, likely due to introduction of Pinus radiata from its native California in the United States. In contrast, Japanese R. roseolus isolates clustered closely with European collections. Phylogenetic differences between Japanese and New Zealand R. roseolus isolates may explain the morphological and biological properties attributed to these geographical variants. The ITS region was subsequently used to design a multiplex PCR for the simultaneous identification of Japanese and New Zealand R. roseolus isolates to track the establishment of ectomycorrhiza on P. radiata seedlings inoculated with commercially valuable R. roseolus. This diagnostic demonstrated the first fruiting of Japanese shoro cultivated on P. radiata in the Southern Hemisphere.


Opposing mechanisms involving RNA and lipids regulate HIV-1 Gag membrane binding through the highly basic region of the matrix domain.
Membrane binding of Gag, a crucial step in HIV-1 assembly, is facilitated by bipartite signals within the matrix (MA) domain: N-terminal myristoyl moiety and the highly basic region (HBR). We and others have shown that Gag interacts with a plasma-membrane-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)], via the HBR, and that this interaction is important for efficient membrane binding and plasma membrane targeting of Gag. Generally, in protein-PI(4,5)P(2) interactions, basic residues promote the interaction as docking sites for the acidic headgroup of the lipid. In this study, toward better understanding of the Gag-PI(4,5)P(2) interaction, we sought to determine the roles played by all of the basic residues in the HBR. We identified three basic residues promoting PI(4,5)P(2)-dependent Gag-membrane binding. Unexpectedly, two other HBR residues, Lys25 and Lys26, suppress membrane binding in the absence of PI(4,5)P(2) and prevent promiscuous intracellular localization of Gag. This inhibition of nonspecific membrane binding is likely through suppression of myristate-dependent hydrophobic interaction because mutating Lys25 and Lys26 enhances binding of Gag with neutral-charged liposomes. These residues were reported to bind RNA. Importantly, we found that RNA also negatively regulates Gag membrane binding. In the absence but not presence of PI(4,5)P(2), RNA bound to MA HBR abolishes Gag-liposome binding. Altogether, these data indicate that the HBR is unique among basic phosphoinositide-binding domains, because it integrates three regulatory components, PI(4,5)P(2), myristate, and RNA, to ensure plasma membrane specificity for particle assembly.


Limiting brain and lung damage after coronary artery bypass grafting: an alternative to conventional coronary artery bypass graft.
The development of coronary artery bypass graft (CABG) for the treatment of coronary heart disease has resulted in reduced morbidity and mortality compared with medical therapy. Even with the rapid development of improved percutaneous interventions, CABG remains an important approach for treating patients with advanced coronary heart disease. However, recent studies and commentary reporting an alarmingly high incidence of subtle, cognitive decline following CABG have generated questions about whether these adverse outcomes could be lessened. Even after considerable study, there is no consensus as to the cause of brain and lung injury after CABG and cardiopulmonary bypass, nor an agreed upon, mechanistic approach to study its prevention. The potential causes of these adverse outcomes and a simple approach are described, involving the use of the cannulae, biventricular pulsatile flow pump, and a blood substitute to optimize the perfusion of brain and alveolar cells, minimize systemic microembolization, and limit post-CABG cognitive decline.


Anti-EGFR antibody reduces lung nodules by inhibition of EGFR-pathway in a model of lymphangioleiomyomatosis.
EGFR belongs to the HER/ErbB family of tyrosine kinase receptors and its activation in cancer cells has been linked with increased proliferation, angiogenesis, and metastasis. Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that occurs sporadically or in association with tuberous sclerosis complex (TSC), a genetic, multisystem disorder characterized by hamartomas in several organs. From chylous of a LAM/TSC patient, we previously isolated smooth muscle-like LAM/TSC cells whose proliferation depends on EGF and monoclonal anti-EGFR antibodies reduced proliferation and caused cell death. We demonstrated that the dependency from EGF was caused by the absence of tuberin. To study the role of EGFR pathway in vivo, we developed a mouse model by administration of LAM/TSC cells to female nude mice. LAM/TSC cells caused pulmonary airspace enlargement and, after 30 weeks, nodule formation which express EGFR. Anti-EGFR antibody decreased the number and dimension of lung nodules likely for the inhibition of Erk and S6 signaling, reversed the pulmonary alterations, and reduced lymphatic and blood vessels. Moreover, in pulmonary nodules anti-EGFR antibody reduced the positivity to estrogen and progesterone receptors which enhance survival of LAM cells and Snail expression. These results suggest that the inhibition of EGFR signalling has a potential in treatment of LAM/TSC lung alterations.


Examining implementation of contingency management in real-world settings.
Very little is known about how reward programs are implemented in real-world substance use treatment settings and whether training in contingency management (CM), an empirically supported rewards-based intervention, impacts their design quality. Providers (N = 214) completed surveys assessing CM beliefs, training, and practices related to use of tangible rewards in treatment. For providers reporting they had not used rewards in treatment previously (54%, n = 116), we assessed beliefs about and interest in adopting a reward-based program. For those endorsing prior reward experience (46%, n = 98), we assessed the features and delivery of rewards and the relation of reward-based intervention training to 4 parameters related to CM efficacy: reinforcement magnitude, immediacy, frequency, and escalation. Among providers without reward experience, endorsement of supportive statements about CM predicted interest in adopting a rewards-based program. Providers with reward experience most often targeted treatment attendance and engaged in behaviors likely to decrease the effectiveness of the intervention, including use of low magnitudes (≤ $25/client), delayed reinforcement, failure to escalate reward values, and offering reward opportunities less than weekly. Providers with longer durations of training were more likely to engage in behaviors consistent with effective CM, including larger magnitude rewards and immediate delivery of rewards. Results indicate that real-world treatment clinics are using reward-based programs but not in ways consistent with research protocols. Longer training exposure is associated with greater adherence to some aspects of CM protocol design. Other evidence-based design features are not being implemented as recommended, even with training. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


[Stereotactic radiosurgery for epilepsy related to hypothalamic hamartoma].
Hypothalamic hamartoma (HH) is a dysplastic lesion fused with hypothalamus and followed by epilepsy, precocious puberty and behavioral disorders. Up to 50% of patients become free of seizures after surgery, but various complications occur in 1/4 of cases. Radiofrequency thermocoagulation, laser interstitial thermal therapy and stereotactic radiosurgery (SRS) are alternative treatment options. To define the indications for SRS in patients with HH and to clarify the irradiation parameters. Twenty-two patients with HH and epilepsy underwent SRS at the Moscow Gamma-knife Center. A retrospective analysis included 19 patients with sufficient follow-up data. Median age of patients was 11.5 years (range 1.3-25.8). The diameter of irradiated HHs ranged between 5.5 and 40.9 mm. In 8 (36%) cases, the volume of hamartoma exceeded 3 cm3. Mean prescribed dose was 18±2.0 Gy, mean prescribed isodose - 48±4.2%. Median follow-up period was 14.8 months (range 3.4 - 96.1). Three (15.8%) patients were free of seizures. One patient (5.3%) improved dramatically after treatment with compete resolution of generalized seizures and experienced only rare emotional seizures (Engel IB). Eleven (57.8%) patients reported lower incidence of seizures. Severity and incidence of seizures were the same in 4 patients (21.1%). The best results were achieved in mean target dose over 20-22 Gy, minimal target dose over 7-10 Gy, covering by the prescribed dose of at least 70-80% of hamartoma volume, as well as in patients with the prescribed dose of 12 Gy delivered to almost entire volume of tumor. None patient had any complications after SRS. SRS is safe regarding neurological, endocrine or visual disturbances. Careful patient selection for SRS makes it an effective option for HH-related epilepsy. The best candidates for SRS are children with seizures aged over 1 year, hamartoma <3 cm3 and area of fusion with hypothalamus <150 mm2.


Safety and feasibility of peri-device leakage closure after LAAO: an international, multicentre collaborative study.
Residual peri-device leakage (PDL) is frequent after left atrial appendage occlusion (LAAO). Little is known about management strategies, procedural aspects and outcomes of interventional PDL closure. The aim of this study was to assess the safety and feasibility of PDL closure after LAAO. Fifteen centres contributed data on baseline characteristics, in-hospital and follow-up outcomes of patients who underwent PDL closure after LAAO. Outcomes of interest included acute success and complication rates and long-term efficacy of the procedure. A total of 95 patients were included and a cumulative number of 104 leaks were closed. The majority of PDLs were detected within 90 days (range 41-231). Detachable coils were the most frequent approach (42.3%), followed by the use of the AMPLATZER Vascular Plug II (29.8%) and the AMPLATZER Duct Occluder II (17.3%). Technical success was 100% with 94.2% of devices placed successfully within the first attempt. There were no major complications requiring surgical or transcatheter interventions. During follow-up (96 days [range 49-526]), persistent leaks were found in 18 patients (18.9%), yielding a functional success rate of 82.7%, although PDLs were significantly reduced in size (pre-leak sizemax: 6.1±3.6 mm vs post-leak sizemax: 2.5±1.3 mm, p<0.001). None of the patients had a leak >5 mm. Major adverse events during follow-up occurred in 5 patients (2 ischaemic strokes, 2 intracranial haemorrhages, and 1 major gastrointestinal bleeding). Several interventional techniques have become available to achieve PDL closure. They are associated with high technical and functional success and low complication rates.


The Ras inhibitors caveolin-1 and docking protein 1 activate peroxisome proliferator-activated receptor γ through spatial relocalization at helix 7 of its ligand-binding domain.
Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that promotes differentiation and cell survival in the stomach. PPARγ upregulates and interacts with caveolin-1 (Cav1), a scaffold protein of Ras/mitogen-activated protein kinases (MAPKs). The cytoplasmic-to-nuclear localization of PPARγ is altered in gastric cancer (GC) patients, suggesting a so-far-unknown role for Cav1 in spatial regulation of PPARγ signaling. We show here that loss of Cav1 accelerated proliferation of normal stomach and GC cells in vitro and in vivo. Downregulation of Cav1 increased Ras/MAPK-dependent phosphorylation of serine 84 in PPARγ and enhanced nuclear translocation and ligand-independent transcription of PPARγ target genes. In contrast, Cav1 overexpression sequestered PPARγ in the cytosol through interaction of the Cav1 scaffolding domain (CSD) with a conserved hydrophobic motif in helix 7 of PPARγ's ligand-binding domain. Cav1 cooperated with the endogenous Ras/MAPK inhibitor docking protein 1 (Dok1) to promote the ligand-dependent transcriptional activity of PPARγ and to inhibit cell proliferation. Ligand-activated PPARγ also reduced tumor growth and upregulated the Ras/MAPK inhibitors Cav1 and Dok1 in a murine model of GC. These results suggest a novel mechanism of PPARγ regulation by which Ras/MAPK inhibitors act as scaffold proteins that sequester and sensitize PPARγ to ligands, limiting proliferation of gastric epithelial cells.


Homodimers of mutant tryptophan synthase alpha-subunits in Escherichia coli.
Tryptophan synthase alpha-subunit from Escherichia coli functionally exists as a heterotetramer of alpha(2)beta(2) with beta-subunit. While wild-type and mutant (F139W, T24M/F139W, and T24L/F139W) alpha-subunits were expressed as a monomer from recombinant plasmids in Escherichia coli, T24A/F139W, T24S/F139W, and T24K/F139W mutant alpha-subunits were abnormally expressed as soluble homodimers in addition to monomers. Monomers of dimer-forming mutant alpha-subunits retain high affinity to beta-subunit, high activity in stimulating catalytic activities of beta-subunit, and nearly intact content of secondary structure, indicating that the global structures of these monomers are identical to that of F139W alpha-subunit. However, fluorescence spectra of Trp139 and ANS binding indicate that significant perturbations occur in the mutant proteins. Interestingly, these defective properties of monomers caused by residue replacement were partially repaired by the dimer formation. As a result, it is suggested that dimers may be formed by domain or loop swapping, and that residue 24 may play important role in maintaining on-pathway of alpha-subunit folding.


Gene Expression Analyses Reveal Mechanisms of Inhibited Yellowing by Applying Selenium-Chitosan on Fresh-Cut Broccoli.
The yellowing of green broccoli is a phenomenon that indicates a serious deterioration of freshness. The green broccoli has been more popular than the yellow one, with its higher nutritional value. Chitosan coating has been employed in vegetables for green-keeping, owing to its functions of regulating chlorophyll metabolism and antioxidant defense. Furthermore, selenium was commonly utilized in the pre-harvest of fruit and vegetables as an antioxidant and chlorophyll regulator. However, there have not yet been concerns about the effects of selenium-chitosan on vegetable yellowing. This study first investigated the impact of selenium-chitosan on the quality of fresh-cut broccoli yellowing during storage by analyzing the chromatic aberration and phytochromes. Additionally, then, the gene expression related to chlorophyll metabolism (POR, CAO, HO, CHLI, NYC1), carotenoid metabolism (VDE, CCS, LCYE, ZEP, HYD), and transcription factors (NAC92, ZIPPER, bHLH66, APL, PIF4) were analyzed using the RT-qPCR technique. Test results showed that treatment with selenium-chitosan can slow down the reduction in h° (Hue angle values) and reduce ethylene release rate and respiration intensity. Via the molecular approach, it was further identified that this treatment could inhibit chlorophyll degradation and carotenoid biosynthesis, accompanied by lower expression levels of heme oxygenase (HO), chlorophyllide A oxygenase (CAO), violaxanthin de-epoxidase (VDE), β-carotene 3-hydroxylase (HYD), NAC92, basic leucine zipper (ZIPPER), bHLH66, PIF4 and APL, and higher expression levels of magnesium chelatase subunit I (CHLI) and lycopene ε-cyclase (LCYE) genes. This work can be used to explore the molecular mechanism of selenium-chitosan in inhibiting the yellowing of fresh-cut broccoli. This study will be of great economic importance in marketing and export by increasing the shelf life of fruits and vegetables.


Novel therapies for meningiomas.
Although advances in surgery, radiation therapy and stereotactic radiosurgery have significantly improved the treatment of meningiomas, there remains an important subset of patients who remain refractory to conventional therapy. Treatment with chemotherapeutic agents such as hydroxyurea and alpha-interferon has provided minimal benefit. In this review, the role of newly emerging novel therapies for meningiomas, with a focus on targeted molecular agents, will be discussed.


[Regulation of apoptosis in aggressive fibroblasts].
Apoptosis is a central physiological mechanism for maintaining cellular stability in tissue. Synovial fibroblasts, which play a central role in the pathogenesis of rheumatoid arthritis (RA), show a resistance to apoptosis. Several molecular mechanisms are involved in such resistance. Thus, soluble Fas can bind Fas ligands (Fas-L) and hinder Fas-L induced apoptosis in fibroblasts. SUMO-1 (a small ubiquitin-like modifier) attaches to proteins post-translationally. This appears to be significantly involved in apoptosis resistance in RA fibroblasts. SUMO-1 levels are substantially increased in synovial fibroblasts from RA patients. A change in the post-translational SUMOlation pattern could represent a new target for changing the stable activation of synovial fibroblasts in RA.


[Heart Transplantation: Treatment for children and adolescents with end-stage heart disease.].
Heart transplantation, which is the recently accepted treatment for children and adolescents with end stage heart disease, is the subject of this review article. Issues such as selection of patients, follow up and management post transplant are discussed, as well as the surgical procedure and the immediate postoperative management. Results from recent studies of long term survival following pediatric heart transplantation are discussed. Short term survival following heart transplantation is now excellent but limited long term follow-up data is available as this operation has only been performed for about two decades. One year survival is now over 90% and five year survival is estimated to be close to 70% in major transplant centers around the world. Post transplant coronary artery disease is mainly responsible for the decreased long term survival. Complications of immunosuppression such as infections, lymphoprolifrative disorders and depressed renal function are still common but usually not life threatening. Non-compliance with medication was observed amongst teenage recipients and can have lethal consequences. Despite this, it has been shown that heart transplantation can provide good quality of life and prolong survival in pediatric patients with end-stage heart disease.


Examining the match between assessed eating disorder recovery and subjective sense of recovery: preliminary findings.
This study examined how individuals, clinically assessed as fully or partially recovered from an eating disorder (ED), subjectively perceived themselves in terms of stage of change in the recovery process. Individuals formerly seen for an ED at a Midwestern clinic were recruited. Using validated definitions of recovery, 18 were fully recovered (physical, behavioural and psychological recovery), and 15 were partially recovered (only physical and behavioural recovery); these groups were compared on overall stage of change and confidence related to this stage, dieting stage of change and internality of motivation. The fully and partially recovered groups endorsed being fully recovered (overall and for dieting) at similar rates. There were trends for the fully recovered group seeking change primarily for themselves and being more confident in their stage of change choice. Results have implications for approaches when a client's assessed recovery stage does not match her subjective sense of recovery and for better understanding recovery from an ED.


Polyimide-Derived Carbon-Coated Li4Ti5O12 as High-Rate Anode Materials for Lithium Ion Batteries.
Carbon-coated Li4Ti5O12 (LTO) has been prepared using polyimide (PI) as a carbon source via the thermal imidization of polyamic acid (PAA) followed by a carbonization process. In this study, the PI with different structures based on pyromellitic dianhydride (PMDA), 4,4'-oxydianiline (ODA), and p-phenylenediamine (p-PDA) moieties have been synthesized. The effect of the PI structure on the electrochemical performance of the carbon-coated LTO has been investigated. The results indicate that the molecular arrangement of PI can be improved when the rigid p-PDA units are introduced into the PI backbone. The carbons derived from the p-PDA-based PI show a more regular graphite structure with fewer defects and higher conductivity. As a result, the carbon-coated LTO exhibits a better rate performance with a discharge capacity of 137.5 mAh/g at 20 C, which is almost 1.5 times larger than that of bare LTO (94.4 mAh/g).


Adhesion of stainable, calcium-rich deposits on substrata with different surface free energies. An in vivo study in beagle dogs.
Calculus plays an important role in chronic inflammatory periodontal disease and tooth loss. Patients can suffer from calculus formation despite good oral hygiene. The strength of adhesion between calculus and the enamel surface, though not determinant for the formation of calculus itself, determines whether calculus remains on the teeth during eating and toothbrushing. In this study, the amount and the strength of adhesion of calcium-rich deposits formed in vivo on different materials are related to substrate surface free energies (sfe). In 4 beagle dogs, fenestrated crowns were made on the upper fourth premolars. Smooth facings of glass (sfe 120 mJ.m-2), polished bovine enamel (sfe 85 mJ.m-2), polymethylmethacrylate (PMMA sfe 56 mJ.m-2) and polytetafluorethylene (PTFE sfe 20 mJ.m-2) were inserted in the crowns for 1, 3, 7, 14 or 28 days. The amount of deposit was evaluated both gravimetrically and planimetrically using Alizarin Red S for staining. Adhesion of calcium-rich deposits was evaluated planimetrically by studying their removal in a brushing machine. Dry weight increased linearly with time (approximately 0.18 mg.cm-2 per day) and was slightly less on PTFE than on the other materials. After 1 to 3 days, staining already revealed a 100% coverage by calcium-rich deposits. The number of strokes required to reduce the planimetric scores by 63% was extremely small on PTFE and PMMA and related with substrate surface free energies. This study shows that a possible way to reduce calculus formation in vivo is to decrease the surface free energy of the enamel using appropriate surfactants in, e.g., toothpastes.


Novel pathogenetic mechanism in a clinical isolate of Yersinia enterocolitica KU14.
Yersinia enterocolitica induces a broad range of gastrointestinal syndromes, including acute enteritis. We previously reported that the clinical isolate, Y. enterocolitica KU14, which lacks pYV, was still capable of causing clinical infection. The present study demonstrated that KU14 did not trigger the death of macrophages in vitro, unlike WA-314 (ATCC51871, which harbors the pYV virulence plasmid). However, the intracellular growth of KU14 in the macrophages was greater than that of WA-C (ATCC51872, a non-plasmid harboring the derivative pYV plasmid). Treatment with a cholesterol-binding drug (beta-cyclodextrin) that affected lipid rafts resulted in a dramatic reduction in the intracellular growth of KU14. These data clearly indicate that the enhanced intracellular growth of KU14 is related to lipid raft-mediated infection.


Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia.
Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce. We generated zebrafish models of IDH2R172K and IDH2R140Q AML and reported their pathologic, functional and transcriptomic features and therapeutic responses to target therapies. Transgenic embryos co-expressing FLT3ITD and IDH2 mutations showed accentuation of myelopoiesis. As these embryos were raised to adulthood, full-blown leukemia ensued with multi-lineage dysplasia, increase in myeloblasts and marrow cellularity and splenomegaly. The leukemia cells were transplantable into primary and secondary recipients and resulted in more aggressive disease. Tg(Runx1:FLT3ITDIDH2R172K) but not Tg(Runx1:FLT3ITDIDH2R140Q) zebrafish showed an increase in T-cell development at embryonic and adult stages. Single-cell transcriptomic analysis revealed increased myeloid skewing, differentiation blockade and enrichment of leukemia-associated gene signatures in both zebrafish models. Tg(Runx1:FLT3ITDIDH2R172K) but not Tg(Runx1:FLT3ITDIDH2R140Q) zebrafish showed an increase in interferon signals at the adult stage. Leukemic phenotypes in both zebrafish could be ameliorated by quizartinib and enasidenib. In conclusion, the zebrafish models of IDH2 mutated AML recapitulated the morphologic, clinical, functional and transcriptomic characteristics of human diseases, and provided the prototype for developing zebrafish leukemia models of other genotypes that would become a platform for high throughput drug screening.


A general prediction model for the detection of ADHD and Autism using structural and functional MRI.
This work presents a novel method for learning a model that can diagnose Attention Deficit Hyperactivity Disorder (ADHD), as well as Autism, using structural texture and functional connectivity features obtained from 3-dimensional structural magnetic resonance imaging (MRI) and 4-dimensional resting-state functional magnetic resonance imaging (fMRI) scans of subjects. We explore a series of three learners: (1) The LeFMS learner first extracts features from the structural MRI images using the texture-based filters produced by a sparse autoencoder. These filters are then convolved with the original MRI image using an unsupervised convolutional network. The resulting features are used as input to a linear support vector machine (SVM) classifier. (2) The LeFMF learner produces a diagnostic model by first computing spatial non-stationary independent components of the fMRI scans, which it uses to decompose each subject's fMRI scan into the time courses of these common spatial components. These features can then be used with a learner by themselves or in combination with other features to produce the model. Regardless of which approach is used, the final set of features are input to a linear support vector machine (SVM) classifier. (3) Finally, the overall LeFMSF learner uses the combined features obtained from the two feature extraction processes in (1) and (2) above as input to an SVM classifier, achieving an accuracy of 0.673 on the ADHD-200 holdout data and 0.643 on the ABIDE holdout data. Both of these results, obtained with the same LeFMSF framework, are the best known, over all hold-out accuracies on these datasets when only using imaging data-exceeding previously-published results by 0.012 for ADHD and 0.042 for Autism. Our results show that combining multi-modal features can yield good classification accuracy for diagnosis of ADHD and Autism, which is an important step towards computer-aided diagnosis of these psychiatric diseases and perhaps others as well.


HLA complex group 11 is involved in colorectal carcinoma cisplatin resistance via the miR-214-5p/SOX4 axis.
The aim of the present study was to investigate the roles and potential mechanisms of long non-coding RNA HLA complex group 11 (HCG11) in colorectal carcinoma. Reverse transcription-quantitative PCR was used to detect HCG11 expression in clinical tissues and survival analysis was performed to identify its prognostic value. In order to investigate its specific biological functions in colorectal carcinoma, the transfection technique was used for the knockdown and overexpression of HCG11. Dual-luciferase reporter gene and RNA pull-down assays were used to identify the binding association between HCG11 and microRNA (miR)-214-5p. Western blot analysis was used to detect the mechanism of epithelial-mesenchymal transition (EMT) regulation in tumor cells in the pathway downstream of HCG11. HCG11 level was high in colorectal carcinoma tissues, which was associated with poor patient prognosis; however, chemotherapy may prevent the upregulation of HCG11 in colorectal carcinoma. HCG11-knockdown suppressed the proliferation, migration and chemotherapeutic sensitivity of colorectal carcinoma cells, whereas HCG11-overexpression enhanced chemotherapeutic sensitivity. miR-214-5p was revealed to be a target gene, and upon direct interaction, a negative regulator of HCG11 in colorectal carcinoma cells. Inhibition of miR-214-5p reversed the restriction of HCG11 on the malignant activity of colorectal carcinoma cells, while miR-214-5p mediated the chemotherapy-related intracellular EMT pathway. In conclusion, HCG11 is a vital oncogene of colorectal carcinoma involved in mediating the chemotherapeutic resistance of tumors.


Development of a magnetic resonance-compatible galvanic skin response measurement system using optic signal.
The purpose of the current study is to develop a magnetic resonance (MR)-compatible galvanic skin response (GSR) measurement system that can measure the GSR signal during MR image acquisition. If GSR signals are measured simultaneously with the acquisition of MR images, there can be a mutual interference effect. The present system was designed to block noises caused by the main magnetic field, the gradient magnetic field, and the radio frequency (RF) pulse when MR images are acquired. To minimize the distortion of MR images, the GSR measurement system was shielded. Especially, this system used analog, not digital, elements in order to remove any possible effects on MR images. An RF-interference-free optical data link using the pulse-width modulation technique was adopted in order to transmit GSR signals measured inside the MR room. The experiment verified that a reliable GSR signal can be obtained without deteriorating the MR image. It is expected that this system can be used for diverse medical and neuroscience studies.


Carriers of factor VII deficiency are not always asymptomatic.
Seven children, referred because of bleeding symptoms, proved to be heterozygotes for factor VII deficiency. Abnormal bruising was the commonest symptom (6/7), followed by postoperative bleeding (4/7). One case had recurrent epistaxis. Results on the patients and their families are presented. Prothrombin times were prolonged by 2-3 s and factor VII assays ranged from 25 to 55% (mean 38%). The cases are reported because they bled excessively: yet it is usually stated that carriers for factor VII deficiency are symptom-free. One case of homozygous factor VII deficiency is also described: the parents (who are heterozygotes) were symptom-free.


Oncolytic activity of a coxsackievirus B3 strain in human endometrial cancer cell lines.
Endometrial cancer (EC) is one of the most common gynecological malignancies globally. Although progress has been made in surgical and other adjuvant therapies, there is still a great need to develop new approaches to further reduce the incidence and mortality of EC. Oncolytic virotherapy offers a novel promising option of cancer treatment and has demonstrated good efficacy in preclinical models and clinical trials. However, only few oncolytic viruses have been tested for EC treatment. In this study, the potential of an oncolytic coxsackievirus B3 (CV-B3) strain 2035A (CV-B3/2035A) was investigated as a novel biotherapeutic agent against EC. Human EC cell lines (Ishikawa, HEC-1-A and HEC-1-B) were infected with CV-B3/2035A, and viral replication and cytotoxic effects were evaluated in vitro. CV-B3/2035A-induced oncolysis was also investigated in nude mice bearing EC xenografts in vivo and in patient-derived EC samples ex vivo. Human EC cell lines expressing different levels of CAR and DAF were all susceptible to infection by CV-B3/2035A and supported efficient viral replication in vitro. In the EC xenograft/nude mouse model, both intratumoral and intravenous administrations of CV-B3-2035A exerted significant therapeutic effects against pre-established EC tumors without causing significant treatment-related toxicity and mortality in nude mice. Moreover, CV-B3/2035A treatment resulted in decreased viability of patient-derived EC samples ex vivo. CV-B3/2035A showed oncolytic activity in human EC cell lines both in vitro and in vivo as well as in patient-derived EC samples ex vivo and thus could be used as an alternative virotherapy agent for the treatment of EC.


Can pharmacy data improve prediction of hospital outcomes? Comparisons with a diagnosis-based comorbidity measure.
The performance of comorbidity measures derived from the hospital discharge abstract, the outpatient pharmacy record, and from both sources combined, were compared in predicting all-cause and unplanned hospital readmission and length of stay. Automated hospital and pharmacy data came from Kaiser-Permanente and included 6721 acute hospitalizations in Southern California from April 1993 to February 1995. The Deyo adaptation of Charlson's 17 comorbidities was derived from hospital discharge data and the 29 Chronic Disease Score (CDS) comorbidity markers were derived from outpatient pharmacy claims data. Logistic and OLS regression models were used to compare the performance of each measure in baseline models and to evaluate whether the CDS contributed additional explanatory power in a combined model. The CDS was a significant predictor of unplanned readmission (C = 0.68) and LOS (Adjusted R(2) = 0.26) in multivariable models adjusted for baseline patient demographic and hospitalization characteristics. The Deyo measure was a significant predictor of all-cause readmission (C = 0.63), unplanned readmission (C = 0.68), and LOS (Adjusted R(2) = 0.26). When pharmacy-based disease markers were added to the Deyo baseline model, modest, statistically significant improvements in predictive power were noted in the unplanned readmission and LOS models. The finding that both measures of comorbid disease demonstrated similar predictive power is noteworthy, because secondary diagnosis data document relevant illness in hospital patients and pharmacy claims data were never intended for that purpose. The results suggest that small improvements in model performance may come from combining both sources of data in models to predict hospital readmission and LOS.


RNA-seq transcriptome profiling of porcine lung from two pig breeds in response to Mycoplasma hyopneumoniae infection.
Mycoplasma hyopneumoniae (Mhp) is the main pathogen causing respiratory disease in the swine industry. Mhp infection rates differ across pig breeds, with Chinese native pig breeds that exhibit high fecundity (e.g., Jiangquhai, Meishan, Erhualian) more sensitive than Duroc, Landrace, and other imported pig breeds. However, the genetic basis of the immune response to Mhp infection in different pig breeds is largely unknown. The aims of this study were to determine the relative Mhp susceptibility of the Chinese native Jiangquhai breed compared to the Duroc breed, and identify molecular mechanisms of differentially expressed genes (DEGs) using an RNA-sequencing (RNA-seq) approach. Jiangquhai and Duroc pigs were artificially infected with the same Mhp dose. The entire experiment lasted 28 days. Daily weight gain, Mhp-specific antibody levels, and lung lesion scores were measured to evaluate the Mhp infection susceptibility of different breeds. Experimental pigs were slaughtered on the 28th day. Lung tissues were collected for total RNA extraction. RNA-seq was performed to identify DEGs, which were enriched by gene ontology (GO) and the Kyoto Encyclopedia annotation of Genes and Genomes (KEGG) databases. DEGs were validated with real-time quantitative polymerase chain reaction (RT-qPCR). Infection with the same Mhp dose produced a more serious condition in Jiangquhai pigs than in Duroc pigs. Jiangquhai pigs showed poorer growth, higher Mhp antibody levels, and more serious lung lesions compared with Duroc pigs. RNA-seq identified 2,250 and 3,526 DEGs in lung tissue from Jiangquhai and Duroc pigs, respectively. The two breeds shared 1,669 DEGs, which were involved in immune-relevant pathways including cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and chemokine signaling pathway. Compared to Jiangquhai pigs, more chemokines, interferon response factors, and interleukins were specifically activated in Duroc pigs; CXCL10, CCL4, IL6 and IFNG genes were significantly up-regulated, which may help Duroc pigs enhance immune response and reduce Mhp susceptibility. This study demonstrated differential immune-related DEGs in lung tissue from the two breeds, and revealed an important role of genetics in the immune response to Mhp infection. The biological functions of these important DEGs should be further confirmed and maybe applied as molecular markers that improve pig health.


Metastatic bone disease: evaluation by functional imaging in correlation with morphologic modalities.
The diagnosis of presence, location and load of metastatic, bone involvement has important implication on patient management and prognosis. This requires collection of data obtained using different imaging modalities. Bone scintigraphy is a highly sensitive and cost-effective screening modality. However, to overcome its lower specificity and its limitation in evaluation of vertebral metastases, CT, PET or MRI can be utilized to verify the nature of suspicious lesions. Expansion of SPECT/ CT may fine tune the highly sensitive bone scintigraphy. PET has an emerging and leading role in many tumors, occasionally obviating the need for bone scintigraphy, particularly in evaluation of response to therapy. PET and whole body MRI offers a potentially important tool to provide the earliest clue of bone marrow metastasis. The value of F-18 PET as a sensitive bone imaging tool needs to be further evaluated on a larger scale in different setting including treated and untreated cancer patients and to evaluate also whether potentially better resolution would lead to more benign lesions detection mimicking metastasis such as fractures, inflammatory, infection, and degenerative involvement of bone. The added value of PET-CT is also to be further examined with this regard.


Two Closely Spaced Aneurysms of the Supraclinoid Internal Carotid Artery: How Does One Influence the Other?
The objective of this study was to use image-based computational fluid dynamics (CFD) techniques to analyze the impact that multiple closely spaced intracranial aneurysm (IAs) of the supra-clinoid segment of the internal carotid artery (ICA) have on each other's hemodynamic characteristics. The vascular geometry of fifteen (15) subjects with 2 IAs was gathered using a 3D digital subtraction angiography clinical system. Two groups of computer models were created for each subject's vascular geometry: both IAs present (model A) and after removal of one IA (model B). Models were separated into two groups based on IA separation: tandem (one proximal and one distal) and adjacent (aneurysms directly opposite on a vessel). Simulations using a pulsatile velocity waveform were solved by a commercial CFD solver. Proximal IAs altered flow into distal IAs (5 of 7), increasing flow energy and spatial-temporally averaged wall shear stress (STA-WSS: 3-50% comparing models A to B) while decreasing flow stability within distal IAs. Thus, proximal IAs may "protect" a distal aneurysm from destructive remodeling due to flow stagnation. Among adjacent IAs, the presence of both IAs decreased each other's flow characteristics, lowering WSS (models A to B) and increasing flow stability: all changes statistically significant (p < 0.05). A negative relationship exists between the mean percent change in flow stability in relation to adjacent IA volume and ostium area. Closely spaced IAs impact hemodynamic alterations onto each other concerning flow energy, stressors, and stability. Understanding these alterations (especially after surgical repair of one IA) may help uncover risk factor(s) pertaining to the growth of (remaining) IAs.


MicroRNA-21 Controls Circadian Regulation of Apoptosis in Atherosclerotic Lesions.
The necrotic core partly formed by ineffective efferocytosis increases the risk of an atherosclerotic plaque rupture. Microribonucleic acids contribute to necrotic core formation by regulating efferocytosis and macrophage apoptosis. Atherosclerotic plaque rupture occurs at increased frequency in the early morning, indicating diurnal changes in plaque vulnerability. Although circadian rhythms play a role in atherosclerosis, the molecular clock output pathways that control plaque composition and rupture susceptibility are unclear. Circadian gene expression, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated at different times of the day in Apoe-/-Mir21+/+ mice and Apoe-/-Mir21-/- mice after consumption of a high-fat diet for 12 weeks. Genome-wide gene expression and lesion formation were analyzed in bone marrow-transplanted mice. Diurnal changes in apoptosis and clock gene expression were determined in human atherosclerotic lesions. The expression of molecular clock genes, lesional apoptosis, and necrotic core size were diurnally regulated in Apoe-/- mice. Efferocytosis did not match the diurnal increase in apoptosis at the beginning of the active phase. However, in parallel with apoptosis, expression levels of oscillating Mir21 strands decreased in the mouse atherosclerotic aorta. Mir21 knockout abolished circadian regulation of apoptosis and reduced necrotic core size but did not affect core clock gene expression. Further, Mir21 knockout upregulated expression of proapoptotic Xaf1 (XIAP-associated factor 1) in the atherosclerotic aorta, which abolished circadian expression of Xaf1. The antiapoptotic effect of Mir21 was mediated by noncanonical targeting of Xaf1 through both Mir21 strands. Mir21 knockout in bone marrow cells also reduced atherosclerosis and necrotic core size. Circadian regulation of clock gene expression was confirmed in human atherosclerotic lesions. Apoptosis oscillated diurnally in phase with XAF1 expression, demonstrating an early morning peak antiphase to that of the Mir21 strands. Our findings suggest that the molecular clock in atherosclerotic lesions induces a diurnal rhythm of apoptosis regulated by circadian Mir21 expression in macrophages that is not matched by efferocytosis, thus increasing the size of the necrotic core.


Self-aligned nanoscale SQUID on a tip.
A nanometer-sized superconducting quantum interference device (nanoSQUID) is fabricated on the apex of a sharp quartz tip and integrated into a scanning SQUID microscope. A simple self-aligned fabrication method results in nanoSQUIDs with diameters down to 100 nm with no lithographic processing. An aluminum nanoSQUID with an effective area of 0.034 microm2 displays flux sensitivity of 1.8 x 10(-6) Phi(0)/Hz(1/2) and operates in fields as high as 0.6 T. With projected spin sensitivity of 65 micro(B)/Hz(1/2) and high bandwidth, the SQUID on a tip is a highly promising probe for nanoscale magnetic imaging and spectroscopy.


Signal mimics derived from a metagenomic analysis of the gypsy moth gut microbiota.
Bacterial signaling is an important part of community life, but little is known about the signal transduction pathways of the as-yet-uncultured members of microbial communities. To address this gap, we aimed to identify genes directing the synthesis of signals in uncultured bacteria associated with the midguts of gypsy moth larvae. We constructed a metagenomic library consisting of DNA extracted directly from the midgut microbiota and analyzed it using an intracellular screen designated METREX, which detects inducers of quorum sensing. In this screen, the metagenomic DNA and a biosensor reside in the same cell. The biosensor consists of a quorum-sensing promoter, which requires an acylhomoserine lactone or other small molecule ligand for activation, driving the expression of the reporter gene gfp. We identified an active metagenomic clone encoding a monooxygenase homologue that mediates a pathway of indole oxidation that leads to the production of a quorum-sensing inducing compound. The signal from this clone induces the activities of LuxR from Vibrio fischeri and CviR from Chromobacterium violaceum. This study is the first to identify a new structural class of quorum-sensing inducer from uncultured bacteria.


Modulation of catalase, copper and zinc in the hippocampus and the prefrontal cortex in social isolation-induced depression in male rats.
Depression is a chronic illness of unknown etiology. Trace elements, such as copper and zinc, and defense antioxidants, such as catalase, are important factors that determine the clinical course of brain diseases. Furthermore, altered glucose metabolism in hippocampus and prefrontal cortex has been associated with depression. Identifying factors that can precipitate depressive-like behavior is of particular importance as it can direct clinicians towards the etiology of the disease. In this study, 16 male Sprague-Dawley rats were randomly divided into two groups: socialized and socially isolated. After one week of acclimatization, animals were housed in isolation for 14 days. Rats in the social group were socialized together for 14 days. On day 15, the forced swim test was performed and blood sugar was analyzed. The brain was removed immediately for biochemical analysis. Socially isolated rats showed more pronounced depressive-like behavior in the forced swim test than socialized rats. Moreover, socially isolated rats demonstrated significantly lower copper and zinc concentrations, as well as a marked reduction in catalase activity, in both prefrontal cortex and hippocampus compared to socialized rats. Additionally, blood sugar levels were higher in socially isolated animals. Isolation causes reduction in copper and zinc levels and catalase activity, which may precipitate depressive-like behavior in these animals.


Dissecting the electromechanical coupling mechanism of the motor-protein prestin.
Prestin, which is a member of the solute carrier 26 anion transporter family (SLC26A5), is a voltage-dependent membrane-based motor protein that confers electromotility on mammalian cochlear outer hair cells (OHCs).1 OHCs are a mammalian innovation, their presence2 and their endowment with functional prestin is essential for normal hearing of mammals.3 In order to clarify the molecular mechanism underlying the voltage-dependent motility of prestin, precise description of the relation between voltage-induced prestin-associated charge movement and the resulting cell displacement is essential. By simultaneously measuring voltage-dependent charge movement, which is manifested in the nonlinear capacitance (NLC) of the cell membrane, and voltage-induced OHC displacement, we provided compelling experimental evidence that prestin-associated charge movement and the resulting electromotility are fully coupled, and that prestin has at least two voltage-dependent conformational transition steps. These findings provide a basis for understanding the molecular mechanism of prestin. Here we discuss the relevance of our finding in the elucidation of the voltage-dependent motor mechanism of prestin, and speculate about possible voltage sensing mechanisms of the molecule.


The distaflo graft: a valid alternative to interposition vein?
the rationale behind the Distaflo graft is inhibition of myointimal hyperplasia through optimisation of haemodynamic forces at the distal anastomosis. This prospective study reports our early clinical results. patients with critical limb ischaemia, but no autologous vein, underwent infrainguinal bypass using Distaflo. Clinical and Duplex assessment provided prospective data from which one year cumulative patency, limb salvage and survival rates were calculated using Kaplan-Meier analysis. Log rank test enabled comparison with an historical control group of Miller cuff grafts. fifty Distaflo were inserted over 29 months into 46 patients, median age 68.5 years, 27 male (59%), of which 27 (54%) were re-do procedures. Proximal anastomoses were to common femoral arteries in 40 cases (80%); distal anastomoses were to popliteal vessels in 20 (40%), and tibial vessels in 30 (60%). The Distaflo graft had patency, limb salvage and survival rates of 39, 50 and 82% respectively compared to 49, 56 and 85% respectively in the control group, with no statistical difference (p = 0.39; 0.65; 0.67 respectively; log rank). in this non-randomised study, the Distaflo has similar one year patency, limb salvage and survival rates to the Miller cuff, potentially justifying its use an alternative in distal prosthetic arterial reconstruction for critical limb ischaemia.


Factors associated with partner violence among female alcoholic patients and their male partners.
This study described the extent of partner violence victimization and perpetration among married or cohabiting female alcoholic patients and the factors associated with it. Male-to-female and female-to-male physical partner violence were examined for 103 female alcoholic patients seeking couples-based outpatient alcoholism treatment. Partner violent (PV) and nonpartner violent (NPV) groups were compared on hypothesized risk factors. In the year before treatment, about two thirds of the women were victimized by their male partners, and a similar proportion engaged in violence toward their male partners. Severe violence also was high, with 22% victimization and 50% perpetration prevalence. Women committed more violent acts overall and were more likely to commit severely violent acts than the men in these couples. Risk factors for PV in both the victimization and perpetration models were as predicted: less education, lower income, greater relationship problems, stronger beliefs in the link between relationship problems and the female patient's drinking, greater cocaine use by the perpetrator of violence and greater emotional distress of the men. Greater alcohol and drug use and more severe alcohol problems also distinguished male perpetrators from their nonviolent counterparts in the female victimization model. Predictions that female patients in the PV group would report greater substance use and problems, childhood violence exposure and emotional distress than their female counterparts in the NPV group were not supported for either victimization or perpetration models. Partner violence is a serious problem for women in alcoholism treatment. More research is needed to increase understanding of risk factors and explanatory models for such violence.


Doppler echocardiographic effects of medetomidine on dynamic left ventricular outflow tract obstruction in cats.
To evaluate the effects of medetomidine on dynamic left ventricular outflow tract (LVOT) obstruction in cats with left ventricular hypertrophy. Clinical trial. 6 domestic shorthair cats with echocardiographic evidence of dynamic LVOT obstruction. Cats were restrained in lateral recumbency, and baseline M-mode and Doppler echocardiographic examinations were performed. An ECG was recorded continuously, and blood pressure was measured indirectly with Doppler instrumentation. Medetomidine (20 microg/kg 19.1 microg/lb]) was then administered i.m., and examinations were repeated 15 minutes later. Significant decreases in heart rate, LVOT velocity, and the LVOT pressure gradient were documented following medetomidine administration. After adjusting for the effects of heart rate by ANCOVA, there were no significant differences in any other systolic or diastolic indices of left ventricular function. Results suggest that administration of medetomidine to cats with dynamic LVOT obstruction may result in elimination of outflow tract obstruction; medetomidine may be a suitable sedative and analgesic agent in this subpopulation of cats.


Ultrasound-guided sacral multifidus plane block for sacral spine surgery: A case report.
Sacral surgeries are a relatively rare type of spine surgery associated with a significant amount of perioperative pain. The paraspinal interfascial or erector spinae plane block is currently being practiced with promising results in cervical, thoracic, and lumbar spine surgeries. It provides not only effective analgesia but also helps in reducing perioperative opioid consumption. Sacral multifidus plane block is one such variant of paraspinal blocks, which may have an equianalgesic profile. This case report describes a novel application of this block for providing perioperative analgesia in sacral spine surgery.


Estimates of Self, Parental and Partner Multiple Intelligences in Iran: A replication and extension.
Two hundred and fifty-eight Iranian university students estimated their own, parents', and partners' overall (general) intelligence, and also estimated 13 'multiple intelligences' on a simple, two-page questionnaire which was previously used in many similar studies. In accordance with previous research, men rated themselves higher than women on logical-mathematical, spatial and musical intelligence. There were, however, no sex differences in ratings of parental and partner multiple intelligences, which is inconsistent with the extant literature. Participants also believed that they were more intelligent than their parents and partners, and that their fathers were more intelligent than their mothers. Multiple regressions indicated that participants' Big Five personality typologies and test experience were significant predictors of self-estimated intelligence. These results are discussed in terms of the cross-cultural literature in the field. Implications of the results are also considered.


Morphology of Phagophore Precursors by Correlative Light-Electron Microscopy.
Autophagosome biogenesis occurs in the transient subdomains of the endoplasmic reticulum that are called omegasomes, which, in fluorescence microscopy, appear as small puncta, which then grow in diameter and finally shrink and disappear once the autophagosome is complete. Autophagosomes are formed by phagophores, which are membrane cisterns that elongate and close to form the double membrane that limits autophagosomes. Earlier electron-microscopy studies showed that, during elongation, phagophores are lined by the endoplasmic reticulum on both sides. However, the morphology of the very early phagophore precursors has not been studied at the electron-microscopy level. We used live-cell imaging of cells expressing markers of phagophore biogenesis combined with correlative light-electron microscopy, as well as electron tomography of ATG2A/B-double-deficient cells, to reveal the high-resolution morphology of phagophore precursors in three dimensions. We showed that phagophores are closed or nearly closed into autophagosomes already at the stage when the omegasome diameter is still large. We further observed that phagophore precursors emerge next to the endoplasmic reticulum as bud-like highly curved membrane cisterns with a small opening to the cytosol. The phagophore precursors then open to form more flat cisterns that elongate and curve to form the classically described crescent-shaped phagophores.


Treatment of coronary in-stent restenosis: a systematic review.
Coronary stent implantation has significantly improved percutaneous coronary intervention and enabled the management of early complications of plain balloon angioplasty. However, a new complication has accompanied these improvements: in-stent restenosis (ISR) arising from neointimal hyperplasia. ISR after coronary angioplasty is currently one of the main limitations of this method, leading to the recurrence of exertional angina pectoris or acute coronary syndromes. The clinical incidence of ISR after bare-metal stent (BMS) implantation is approximately 20%-35%. The use of drug-eluting stents (DES) has led to a further decrease in the occurrence of ISR to 5%-10%. Evidence resulting from controlled clinical studies suggests that DES and drug-eluting balloon catheters (DEB) provide the best clinical and angiographic results in the treatment of ISR. We undertook a systematic review of the pathophysiology, diagnostics and treatment options for BMS- and DES-ISR. We discuss recent randomised studies, comparing different DES or DEB used for BMS or DES-ISR treatment, as well as the use of new biovascular scafolds and the topic of scafold restenosis.


Immunosuppressive effects of vascular endothelial growth factor.
Vascular endothelial growth factor (VEGF) serves a critical role in vasculogenesis, angiogenesis, tumor, inflammatory angiogenesis and lymphangiogenesis. Since 2004, bevacizumab (Avastin), a humanized anti-VEGFA monoclonal antibody, has been approved for the treatment of non-small cell lung, breast, kidney and ovarian cancer in combination with standard chemotherapy. VEGF has been demonstrated to be important in the clinic as a therapeutic target in the anti-angiogenic approach to cancer therapy. The targeting of VEGF, together with immunotherapy, has been reported to be able to reverse the immunosuppressive effects of VEGF. A positive correlation between VEGF expression and the reduced survival rates of patients with cancer has also been demonstrated. Furthermore, increased VEGF expression can lead to immune suppression via the inhibition of dendritic cell maturation, the reduction of T-cell tumor infiltration and the promotion of inhibitory cell types in the tumor microenvironment.


Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone.
Type I diabetes mellitus is caused by autoimmune destruction of pancreatic beta cells, and effective treatment of the disease might require rescuing beta cell function in a context of reinstalled immune tolerance. Sertoli cells (SCs) are found in the testes, where their main task is to provide local immunological protection and nourishment to developing germ cells. SCs engraft, self-protect, and coprotect allogeneic and xenogeneic grafts from immune destruction in different experimental settings. SCs have also been successfully implanted into the central nervous system to create a regulatory environment to the surrounding tissue which is trophic and counter-inflammatory. We report that isolated neonatal porcine SC, administered alone in highly biocompatible microcapsules, led to diabetes prevention and reversion in the respective 88 and 81% of overtly diabetic (nonobese diabetic [NOD]) mice, with no need for additional beta cell or insulin therapy. The effect was associated with restoration of systemic immune tolerance and detection of functional pancreatic islets that consisted of glucose-responsive and insulin-secreting cells. Curative effects by SC were strictly dependent on efficient tryptophan metabolism in the xenografts, leading to TGF-beta-dependent emergence of autoantigen-specific regulatory T cells and recovery of beta cell function in the diabetic recipients.


Reliability of detecting rRNA sequences of Chlamydia trachomatis with fluorescence in situ hybridization without amplification.
To use fluorescence in situ hybridization (FISH) using ribosomal RNA (rRNA) oligonucleotide probes as the target nucleic acid for the detection of Chlamydia trachomatis. Suitable sequences selected from the rRNA sequence of C trachomatis were labeled with a fluorescent dye and used in FISH for detecting chlamydial inclusion bodies and/ or elementary bodies in paraformaldehyde-fixed urogenital swab samples. The sensitivity and specificity of the FISH assay were compared with those of the polymerase chain reaction (PCR) using plasmid primers. Positive known C trachomatis-infected McCoy cells were used as positive controls. Urogenital swab specimens that were C trachomatis negative on culture and PCR were used as negative controls. Among the 128 samples included in the study, FISH was positive in 28 (21.8%) and PCR in 33 (25.7%). A significant correlation was found between the 2 detection methods. Results of PCR and FISH were consistent in 115 of the 128 samples (R = 0.89). Thirteen samples showed discordant results. Of these, 9 FISH negative samples were PCR positive and 4 FISH positive samples were PCR negative. FISH was a highly specific and fairly sensitive technique for detecting C trachomatis. Signal amplification techniques and use of different fluorophores may further increase the sensitivity of this technique.


Analyses of Influence on Chromium Coating after Grinding from the View of Final Microstructure and Microhardness in the Surface Layer.
The article deals with the analysis of chromium layer grinding on a steel substrate, where this issue was addressed with regard to the requirements of the manufacturing sector, specifically in the aerospace industry. The experimental samples were chromium-plated and ground under different cutting conditions by the grooving method of grinding. Two types of grinding wheels for grinding were used, grinding wheel based on SG (solgel) a grinding wheel based on SiC. The resulting microstructure and microhardness in the machined layer were evaluated with using of confocal laser microscopy, inverted materials microscopy, and hardness testing. Based on the results, recommendations were made regarding a suitable approach to grinding the chromium coating. We used a confocal laser microscope and hardness tester for the evaluation of presented values. It was found that, on the base of analyses values, with both grinding wheel and using cutting conditions used, good results have been achieved. This could be stated, because the analysis of the samples microstructure after grinding for the given cutting conditions showed that it is possible that a small influence is completely acceptable from the point of the final product view and there are no major negative phenomena. Measurements of surface microhardness after grinding showed similar results for all samples. The SiC-based grinding wheel showed slightly better results, but both grinding wheels can be used without problems for the presented cutting conditions, and the presented cutting conditions with both grinding wheels can be recommended for the grinding of the given material.


A lifeworld phenomenological study of the experience of living within ageing skin.
Understanding people's experience of skin ageing as it is lived can enable sensitive approaches to promoting healthy skin and to care in general. By understanding the insider perspective, what it is like for individuals, a way to sensitise practice for more humanly sensitive care is offered. Through interviews with seventeen community-dwelling older people, the essential meaning of living within ageing skin was illuminated as a state of managed inevitability. The skin is inevitably changing, and ageing skin is a marker of change over time but the person within remains. Constituents of the phenomenon comprise the experience of unfamiliar sights and sensations given by ageing skin; facing and accepting bodily changes and seeing this back and forth in family connections; taking care of the skin "to face" the world; and to present oneself to others and a different place in the world, same person, changed body. Findings point to why and how nurses can treat older people as persons by not over emphasising a view on ageing bodies or bodies with aged skin alone, but in tempering this view with deeper existential insights, meeting the older person with a skin care need as a person and not just as a physical entity.


Adenoviral diseases in children: a study of 105 hospital cases.
The clinical findings for 105 children hospitalized with adenoviral infection were studied prospectively. In 82 children, the diagnosis was based on the detection of adenovirus antigen in the nasopharyngeal specimens and in 17 children in the feces. In the remaining six patients, findings from nasopharyngeal specimens were negative but a significant increase in CF (complement fixation) titers was detected. The clinical picture of adenoviral infection was characterized by high-grade (mean 39.4 degrees C) and prolonged fever (mean duration 5.4 days). Tonsillitis, otitis, and gastroenteritis were the most common illnesses. In 17% of the patients, no identifiable focus of infection could be demonstrated; nine children with no identifiable focus of infection had febrile convulsions. The WBC count and ESR varied from normal values to values seen in bacterial infections; thus it was difficult to distinguish adenoviral disease from a bacterial disease. Forty-five children were referred to the hospital due to infection unresponsive to antimicrobial therapy. The rapid detection of adenovirus antigen in nasopharyngeal specimens or feces proved to have a great clinical value in the diagnosis of adenoviral infections.


Generation of Rat Monoclonal Antibody for Human IQGAP1 by Immunization of Three-Dimensional-Cultured Cancer Cells.
The scaffold protein IQ motif containing GTPase activating protein 1 (IQGAP1) is an adherens junction component in the epithelial tissue that binds many signaling and structural molecules to regulate biological processes. It is known that IQGAP1 is overexpressed in some tumors. In this study, we produced rat monoclonal antibodies (mAbs) through immunization of the lysate from three-dimensional (3D)-cultured DLD-1 cells to elucidate a characteristic feature of a tumor. In cancer research, 3D-cultured cancer cells are used as an intermediate model between in vitro cancer cell line cultures and in vivo tumors. Our results showed that mAb 7E11 recognized increasing antigen in the lysate of 3D-cultured cells comparing with two-dimensional-cultured cells, and its antigen is the human IQGAP1. Furthermore, we indicated that mAb 7E11 was used in immunoblotting, immunoprecipitation, and immunofluorescence staining. Therefore, it may be useful in the analysis of human cancer.


Pediatric Neuroblastoma - Impact of Nutritional Status on Complications and Outcomes.
The aim is to study the impact of nutritional status on outcomes and treatment-related complications in patients of neuroblastoma. Anthropometry (height, weight, weight for height [in <5 years], mid-arm circumference [MAC] [in <5 years], and body mass index [BMI]), hemoglobin level, and serum albumin level were recorded. Twenty-four neuroblastoma patients, 16 males and 8 females, with a mean age of 42.7 months were treated and followed up over a period of 0.03-170 months. Of 24 patients, 16 survived (complete response - 9, partial response - 2, no response - 2, progressive disease - 3). Height <2 standard deviation [SD] was seen in 12.5% (3/24). Mortality and complications were found in 66.7% (2/3) and 100% (3/3), respectively. Weight <2SD was seen in 37.5% (9/24). Mortality and complications were found in 33.3% (3/9) and 67% (6/9), respectively. Weight for height <2 SD was seen in 35% (7/20). Mortality and complications were found in 42.9% (3/7) and 71.4% (5/7), respectively. MAC <2 SD was seen in 15.8% (3/19). Mortality and complications were found in 66.7% (2/3) and 66.7% (2/3). BMI <2SD was seen in 29.2% (7/24). Mortality and complications were found in 42.8% (3/7) and 28.6% (2/7). Anemia was seen in 62.5% (15/24), of which nine survived. Complications were seen in 58.3% (14/24) (P = 0.001). Hypoproteinemia was seen in 20.8% (5/24). Mortality and complications were 40% (2/5) and 80% (4/5). Neuroblastoma has poor outcome in Indian children, and there does not appear to be a major role played by nutrition in determining the response to treatment and survival.


Design, synthesis and biological evaluation of novel trimethylangelicin analogues targeting nuclear factor kB (NF-kB).
A series of trimethylangelicin (TMA) derivatives were designed and synthesized to overcome the unwanted effects of TMA, promising agent for treatment of inflammation-related diseases and other pathologies, such as cystic fibrosis. The new generation TMA analogues bore hindered substituents at the 4 position in order to minimize or avoid the photoreactions with DNA. Among them, the 4-isopropyl-6-ethyl derivative 23 exhibited TMA-like inhibitory activity on NF-κB/DNA interactions but it proved unable to photoreact with pyrimidine bases of DNA, nor to induce any other DNA damage. The isopropyl analogue 23 was proven to lack mutagenicity when assayed through Ames test and exhibited no anti-proliferative activity on cystic fibrosis IB3-1 cells, displaying at the same time inhibition of the TNF-α induced release of the NF-κB regulated PDGF-B chain, IL-10, IL-15, IL-17 and IFN-γ. Therefore compound 23 deserves further assay to determine its anti-inflammatory properties, since it lacks photoreaction properties and mutagenicity-related side effects.


Pheochromocytoma: diagnostic and therapeutic update.
Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells of the sympathetic nervous system. In 80-85% of cases, these tumors are located in the adrenal medulla while the remainder is located in extra-adrenal chromaffin tissues (paragangliomas). Pheochromocytomas account for 6.5% of incidentally discovered adrenal tumors. These tumors may be sporadic or the result of several genetic diseases: multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and familial paraganglioma associated with mutations in succinate dehydrogenase subunits. Diagnosis of pheochromocytoma should first be established biochemically by measuring plasma free metanephrines and urinary fractionated metanephrines. The radiological imaging tests of choice are computed tomography (CT) or magnetic resonance imaging (MRI). The first-line specific functional imaging test is scintigraphy with (123)I-metaiodobenzylguanidine (MIBG); if this test is unavailable, scintigraphy with (131)I-MIBG is the second choice. Positron emission tomography (PET) with (18)F-F-fluorodopamine (F-DA) is useful in metastatic disease. The treatment of choice is laparoscopic surgery after adequate alpha adrenergic blockade. Approximately 10% of tumors are malignant. Chemotherapy is used for inoperable disease. Prognosis is good except in malignant disease, in which 5-year survival is less than 50%. The identification of the genes causing hereditary pheochromocytoma has led to changes in the recommendation for genetic testing.


CANon: Lightweight and Practical Cyber-Attack Detection for Automotive Controller Area Networks.
Automotive cyber-physical systems are in transition from the closed-systems to open-networking systems. As a result, in-vehicle networks such as the controller area network (CAN) have become essential to connect to inter-vehicle networks through the various rich interfaces. Newly exposed security concerns derived from this requirement may cause in-vehicle networks to pose threats to automotive security and driver's safety. In this paper, to ensure a high level of security of the in-vehicle network for automotive CPS, we propose a novel lightweight and practical cyber defense platform, referred to as CANon (CAN with origin authentication and non-repudiation), to be enabled to detect cyber-attacks in real-time. CANon is designed based on the hierarchical approach of centralized-session management and distributed-origin authentication. In the former, a gateway node manages each initialization vector and session of origin-centric groups consisting of two more sending and receiving nodes. In the latter, the receiving nodes belonging to the given origin-centric group individually perform the symmetric key-based detection against cyber-attacks by verifying each message received from the sending node, namely origin authentication, in real-time. To improve the control security, CANon employs a one-time local key selected from a sequential hash chain (SHC) for authentication of an origin node in a distributed mode and exploits the iterative hash operations with randomness. Since the SHC can constantly generate and consume hash values regardless of their memory capacities, it is very effective for resource-limited nodes for in-vehicle networks. In addition, through implicit key synchronization within a given group, CANon addresses the challenges of a key exposure problem and a complex key distribution mechanism when performing symmetric key-based authentication. To achieve lightweight cyber-attack detection without imposing an additive load on CAN, CANon uses a keyed-message authentication code (KMAC) activated within a given group. The detection performance of CANon is evaluated under an actual node of Freescale S12XF and virtual nodes operating on the well-known CANoe tool. It is seen that the detection rate of CANon against brute-force and replay attacks reaches 100% when the length of KMAC is over 16 bits. It demonstrates that CANon ensures high security and is sufficient to operate in real-time even on low-performance ECUs. Moreover, CANon based on several software modules operates without an additive hardware security module at an upper layer of the CAN protocol and can be directly ported to CAN-FD (CAN with Flexible Data rate) so that it achieves the practical cyber defense platform.


Tumor decellularization reveals proteomic and mechanical characteristics of the extracellular matrix of primary liver cancer.
Tumor initiation and progression are critically dependent on interaction of cancer cells with their cellular and extracellular microenvironment. Alterations in the composition, integrity, and mechanical properties of the extracellular matrix (ECM) dictate tumor processes including cell proliferation, migration, and invasion. Also in primary liver cancer, consisting of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the dysregulation of the extracellular environment by liver fibrosis and tumor desmoplasia is pertinent. Yet, the exact changes occurring in liver cancer ECM remain uncharacterized and underlying tumor-promoting mechanisms remain largely unknown. Herein, an integrative molecular and mechanical approach is used to extensively characterize the ECM of HCC and CCA tumors by utilizing an optimized decellularization technique. We identified a myriad of proteins in both tumor and adjacent liver tissue, uncovering distinct malignancy-related ECM signatures. The resolution of this approach unveiled additional ECM-related proteins compared to large liver cancer transcriptomic datasets. The differences in ECM protein composition resulted in divergent mechanical properties on a macro- and micro-scale that are tumor-type specific. Furthermore, the decellularized tumor ECM was employed to create a tumor-specific hydrogel that supports patient-derived tumor organoids, which provides a new avenue for personalized medicine applications. Taken together, this study contributes to a better understanding of alterations to composition, stiffness, and collagen alignment of the tumor ECM that occur during liver cancer development.


Breast irradiation with brachytherapy: approved techniques and new concepts.
Among surgery and chemotherapy, radiotherapy has an important role in the treatment of breast cancer patients. But not only external beam radiotherapy (EBRT) treatment is an established method for treatment of breast cancer, also brachytherapy (BT) is an approved method. BT is well known for boost irradiation in combination with EBRT, but new indications as re-irradiation for local recurrences or partial breast irradiation offer new aspects in the field of BT for breast cancer treatment. Because of modern CT based 3-D treatment planning systems and the possibility of intensity modulated brachytherapy (IMBT) has getting more potential. In the future for selected patient's re-irradiation of the breast using IMBT after local relapse and second breast conserving surgery might be an alternative instead of mastectomy. Even partial breast BT following breast conservative operation as a new treatment option is getting more and more interesting and is widely investigated in several studies. Due to the approved techniques and the new indications BT is and will be an attractive alternative and extension in the field of breast cancer treatment. But we need five better ten years results for definite conclusions at least.


Blood lymphocyte population 4 to 6 years after adjuvant cyclic chemotherapy for operable breast carcinoma.
The influence of postoperative cyclic chemotherapy for breast carcinoma on the blood lymphocyte population was examined in 21 recurrence-free women 4 to 6 years after completion of therapy. Chemotherapy consisted of combinations of chlorambucil, methotrexate and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil. It was observed that the lymphocyte numbers and mitogenic responses to PHA and in an MLC, known to be depressed during and shortly after treatment, had recovered to the levels of healthy age-matched women. NK activity, which is increased during the period of chemotherapy, still remained elevated.


Pilomatrixoma of Male Breast.
Pilomatrixoma is an uncommon tumour,of the skin and is characterised by transition of b@philic ceffs into shadow ceus. The, present cas6" described here because of certain unusual features namely origin from the male breast, production of hair within the tumour and associaion with mfiltr ductcarcinomaafin of the breast.


[Bilateral Instability of the Interphalangeal Articulation of the Thumb in Hajdu-Cheney Syndrome].
We present the case of a 52-year-old lady suffering from Hajdu-Cheney syndrome, a rare hereditary disease, which was referred to our clinic on the basis of progressive instability of the interpalangeal articulations of both thumbs. Even if acroosteolysis of the distal phalangeal bones is typical for this disease, to the best of our knowledge the interphalangeal instability has not been described before.


The Impact of High-Fat Diet on Mitochondrial Function, Free Radical Production, and Nitrosative Stress in the Salivary Glands of Wistar Rats.
Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups (n = 10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1β and caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.


Comparing the ICSI outcome between different causes of subfertility and estimate the role of IL-1β in predicting ICSI outcome.
Background : The physiological regulation of the ovary is a complicated process ; the growth factor, steroid hormones, gonadotropins, and cytokines all take part. Inflammatory cytokines are found in many compartments of the ovary, such as the follicles. The ovarian tissue produces them in addition to the macrophages. In this study, we aimed to compare the level of serum and follicular fluid IL-1Beta (IL-1β) for different groups of infertile patients, comparing the ICSI outcome between sub-fertile couples due to different causes. The results of this study IL-1β was significantly higher in the patients with unexplained subfertility (p-value < 0.05), no significant difference was found in the ICSI outcome between patients with different causes of subfertility. The lowest pregnancy rate was found in patients with unexplained subfertility, but the difference is insignificant. In conclusion, immunity plays a role in unexplained subfertility as patients with unexplained subfertility have a significantly higher serum level IL-1β than the other causes of subfertility. However, IL-1β does not affect ICSI outcome. Therefore, the ICSI outcome is not affected by the cause of subfertility. J. Med. Invest. 69 : 180-184, August, 2022.


Electronic structure study of seven-coordinate first-row transition metal complexes derived from 1,10-diaza-15-crown-5: a successful marriage of theory with experiment.
A detailed study of the electronic structure of seven-coordinate Mn(II), Co(II), and Ni(II) complexes with the lariat ether N,N'-bis(2-aminobenzyl)-1,10-diaza-15-crown-5 (L(1)) is presented. These complexes represent new examples of structurally characterized seven-coordinate (pentagonal bipyramidal) complexes for the Mn(II), Co(II), and Ni(II) ions. The X-ray crystal structures of the Mn(II) and Co(II) complexes show C(2) symmetries for the [M(L(1))](2+) cations, whereas the structures of the Ni(II) complexes show a more distorted coordination environment. The magnetic properties of the Mn(II) complex display a characteristic Curie law, whereas those of the Co(II) and Ni(II) ions show the occurrence of zero-field splitting of the S = 3/2 and 1 ground states, respectively. Geometry optimizations of the [M(L(1))](2+) systems (M = Mn, Co, or Ni) at the DFT (B3LYP) level of theory provide theoretical structures in good agreement with the experimental data. Electronic structure calculations predict a similar ordering of the metal-based beta spin frontier MO for the Mn(II) and Co(II) complexes. This particular ordering of the frontier MO leads to a pseudodegenerate ground state for the d(8) Ni(II) ion. The distortion of the C(2) symmetry in [Ni(L(1))](2+) is consistent with a Jahn-Teller effect that removes this pseudodegeneracy. Our electronic structure calculations predict that the binding strength of L(1) should follow the trend Co(II) approximately Mn(II) > Ni(II), in agreement with experimental data obtained from spectrophotometric titrations.


Neonatal lupus erythematosus.
We present a case of neonatal lupus erythematosus (NLE) in a black infant presenting with symmetrical depigmented macules on the face resembling vitiligo. NLE is a rare condition affecting newborn infants of mothers who have connective tissue disease, with or without autoantibodies to extractable nuclear antigens Ro (SS-A), La (SS-B) or ribonucleoproteins. Infants present with cutaneous lesions or congenital heart block or both. The skin lesions are usually annular and erythematous and transient and resemble those of subacute cutaneous lupus erythematosus. The presentation of this patient was therefore striking.


Elucidation of removal processes in sequential biofiltration (SBF) and soil aquifer treatment (SAT) by analysis of a broad range of trace organic chemicals (TOrCs) and their transformation products (TPs).
Many chemicals with different physico-chemical properties are present in municipal wastewater. In this study, the removal of a broad range of trace organic chemicals (TOrCs) was determined in two biological treatment processes differing in hydraulic retention time: sequential biofiltration (SBF) and soil-aquifer treatment (SAT), operated in Germany and Spain. Occurrence and the degree of removal of more than 150 TOrCs with different physico-chemical properties were analysed, including precursors as well as human metabolites and environmental transformation products (TPs). Ninety TOrCs were detected in the feed water of the SBF system, 40% of these showed removal efficiencies of higher than 30% during biological treatment. In SAT, 70 TOrCs were detected in the feed water, 60% of these could be reduced by more than 30% after approximately 3 days of subsurface treatment. For uncharged and negatively charged TOrCs biological degradation was mainly responsible for the removal, while positively charged TOrCs were most likely also removed by ionic interactions. The detections of TPs confirmed that biodegradation was a major removal process in both systems. The analysis of positively and negatively charged, neutral and zwitterionic TOrCs and the simultaneous analysis of precursors and their biologically formed TPs enabled a detailed understanding of underlying mechanisms of their removal in the two systems. On this basis, criteria for site-specific indicator selection were proposed.


Determination of paclitaxel in human plasma following the administration of Genaxol or Genetaxyl by liquid chromatography/tandem mass spectrometry.
A sensitive and specific assay for paclitaxel in plasma has been developed to overcome limitations in previously published assays, using liquid chromatography with tandem mass spectrometric detection. Plasma samples (100 microL) were subjected to liquid-liquid extraction with 1-chlorobutane/acetonitrile (4:1, v/v), with [(2)H(5)]paclitaxel employed as the internal standard. Chromatography was carried out with a Waters SymmetryShield C8 column (50 x 2.1 mm, 3.5 microm). The total run time, including equilibration, was 8 min, using a gradient of acetonitrile and 10 mM ammonium formate, pH 4.0. The assay is accurate and precise over the range of 2-2500 ng/mL and has been successfully applied to study the clinical pharmacokinetics of two formulations of paclitaxel, Genaxol and Genetaxyl, given orally and intravenously.


[Activity of the disease and selected echocardiographic abnormalities in ankylosing spondylitis].
Cardiovascular involvement in the course of ankylosing spondylitis (AS) is a very important problem. The aim was to assess the influence of the activity of the disease on echocardiographic abnormalities in ankylosing spondylitis. We studied 38 AS patients. Activity of the disease was assessed according to the ESR and following indexes: BASMI, BASFI, BASDAI, BASG-t, BASG-6. Using 2-dimensional echo Doppler (Acuson 128XP) the heart dimensions were determined according to the American Society of Echocardiography guidelines. Patients with mitral valve prolapse compared with the group of the AS patients without this abnormality had significant higher (p = 0.05) activity of the disease assessed by ESR. Patients with aortic incompetence compared with the group of the AS patients without this abnormality, had significant (p = 0.04) lower disease activity assessed by BASG-6. We found significant negative correlation between EF and disease duration, and significant lower disease activity assessed by BA SG-6. Patients with pericardial effusion compared with group without this had significant shorter (p = 0.05) disease duration. There was no significant influence of the following indexes: BASMI, BASFI, BASDAI, BASG-t, BASG-6 of the activity of the disease on echocardiographic abnormalities in ankylosing spondylitis.


Improvement of a porcine somatic cell nuclear transfer technique by optimizing donor cell and recipient oocyte preparations.
This study was conducted to improve a porcine somatic cell nuclear transfer (SCNT) technique by optimizing donor cell and recipient oocyte preparations. Adult and fetal fibroblasts, and cumulus and oviduct cells were used as donor cells, and in vivo- and in vitro-matured oocytes were employed as recipient oocytes. The percentages of fusion and development to the blastocyst stage, the ratio of blastocysts to 2-cell embryos, and cell number of blastocysts were monitored as experimental parameters. In Experiment 1, donor cells of four different types were transferred to enucleated oocytes matured in vitro, and more (P < 0.05) blastocysts were derived from SCNT of fetal fibroblasts than from that of other cells (15.9% versus 3.1-7.9%). For SCNT using fetal fibroblasts, increasing the number of subcultures up to 15 times did not improve developmental competence to the blastocyst stage (12.2-16.7%). In Experiment 2, fetal fibroblasts were transferred to enucleated oocytes that matured in vivo or in vitro. When parthenogenetic activation of both types of oocytes was conducted as a preliminary control treatment, a significant increase in blastocyst formation was found for in vivo-matured compared with in vitro-matured oocytes (36.4% versus 29.5%). However, no improvement was achieved in SCNT using in vivo-matured oocytes. In conclusion, the type of donor somatic cell is important for improving development after porcine SCNT, and fetal fibroblasts were the most effective among examined cells. A system with good reproducibility has been established using fetal fibroblasts as the donor karyoplast after subculturing 1-10 times, and using both in vivo and in vitro-matured oocytes as the recipient cytoplast.


Several clinical interests regarding lung volume reduction surgery for severe emphysema: meta-analysis and systematic review of randomized controlled trials.
We aim to address several clinical interests regarding lung volume reduction surgery (LVRS) for severe emphysema using meta-analysis and systematic review of randomized controlled trials (RCTs). Eight RCTs published from 1999 to 2010 were identified and synthesized to compare the efficacy and safety of LVRS vs conservative medical therapy. One RCT was obtained regarding comparison of median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS). And three RCTs were available evaluating clinical efficacy of using bovine pericardium for buttressing, autologous fibrin sealant and BioGlue, respectively. Odds ratio (95%CI), expressed as the mortality of group A (the group underwent LVRS) versus group B (conservative medical therapies), was 5.16(2.84, 9.35) in 3 months, 3(0.94, 9.57) in 6 months, 1.05(0.82, 1.33) in 12 months, respectively. On the 3rd, 6th and 12th month, all lung function indices of group A were improved more significantly as compared with group B. PaO2 and PaCO2 on the 6th and 12th month showed the same trend. 6MWD of group A on the 6th month and 12th month were improved significantly than of group B, despite no difference on the 3rd month. Quality of life (QOL) of group A was better than of group B in 6 and 12 months. VATS is preferred to MS, due to the earlier recovery and lower cost. And autologous fibrin sealant and BioGlue seems to be the efficacious methods to reduce air leak following LVRS. LVRS offers the more benefits regarding survival, lung function, gas exchange, exercise capacity and QOL, despite the higher mortality in initial three postoperative months. LVRS, with the optimization of surgical approach and material for reinforcement of the staple lines, should be recommended to patients suffering from severe heterogeneous emphysema.


Monitoring for postnatal hearing loss using risk factors: a systematic literature review.
The aim of this study was to investigate whether there was evidence-based support for targeted surveillance programs using a risk-factor registry to detect postnatal hearing loss or whether other programs were available that may be more effective than targeted surveillance. Particularly, it addressed questions that arose along the targeted surveillance pathway, including: (1) the risk factors used to determine a referral, (2) referral frequencies, (3) the relationship between risk factors and a postnatal hearing loss, and (4) other systems that may be more efficient than the use of risk factors. A systematic literature review was completed in peer-reviewed and non-peer-reviewed databases. Publications were obtained using the databases MEDLINE, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica on line, and by inspecting the reference lists of relevant articles and expert-committee papers. Quality assessment ratings and data extraction were completed by the research team. In total, 40 articles met the inclusion criteria and were included in this review. The outcomes drawn from these studies were inconclusive as they were based on small sample sizes and largely from single sites only. With this in mind, from the information obtained: (1) gestational age, low-birth weight, toxoplasmosis, other infections, rubella, cytomegalovirus (CMV), herpes simplex virus infections, craniofacial anomalies, respirator support, and the administration of aminoglycosides were the more commonly reported risk factors in programs; (2) referral frequency for monitoring appointments was approximately 3%; and (3) CMV, extracorporeal membrane oxygenation, congenital diaphragmatic hernia, and persistent pulmonary hypertension of the newborn were associated with postnatal hearing loss, whereas, preauricular skin tags and ear pits, low-birth weight, and toxoplasmosis were not. The review also identified that second-phase universal screening programs, CMV screening, and genetic screening should be explored as potential additions or alternatives to targeted surveillance using risk factors. Further large-scale, population-based research on available programs for the detection of postnatal hearing loss should be conducted to improve present practice and assist with the development of evidence-based guidelines for hearing monitoring.


Calycindaphines A-J, Daphniphyllum alkaloids from the roots of Daphniphyllum calycinum.
Ten new Daphniphyllum alkaloids, calycindaphines A-J (1-10), together with seventeen known alkaloids were isolated from the roots of Daphniphyllum calycinum. Their structures were established by extensive spectroscopic methods and compared with data from literature. Compound 1 is a novel alkaloid with a new rearrangement C22 skeleton with the 5/8/7/5/5 ring system. Compound 2 represents the second example of calyciphylline G-type alkaloids. Compound 10 is the first example of secodaphniphylline-type alkaloid absent of the oxygen-bridge between C-25/C-29. The possible biogenetic pathways of 1 and 2 were also proposed. All the isolated compounds were evaluated for their bioactivities in three cell models. Compounds 22, 23, and 26 showed significant NF-κB transcriptional inhibitory activity at a concentration of 50 μM. Compounds 16 and 18 exhibited significant TGF-β inhibitory activity in HepG2 cells. Compounds 24 and 26 induced autophagic puncta and mediated the autophagic marker LC3-II conversion in HEK293 cells.


Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(-/-) mouse.
Cytokines and growth factors are thought to contribute to skeletal muscle hypertrophy. Leukemia inhibitory factor (LIF), a cytokine, enhances skeletal muscle regeneration; however the role of LIF in skeletal muscle hypertrophy remains uncertain. We examined the hypertrophic ability of the plantaris and soleus muscles in wild-type mice (WT) and LIF knock-out mice [LIF(-/-)] in response to increased mechanical load. Using the functional overload model to induce increases in mechanical load on the plantaris and soleus muscle, WT mice demonstrated increases in plantaris and soleus mass after 7, 21, and 42 days of loading. However, the LIF(-/-) mice had no significant increases in plantaris muscle mass at any time point, while the soleus muscle exhibited a delayed hypertrophic response. Systemic delivery of LIF to the LIF(-/-) mice returned the hypertrophic response to the same levels as the WT mice after 21 days of functional overload. These data demonstrate for the first time that LIF expression in loaded skeletal muscle is critical for the development of skeletal muscle hypertrophy in the functional overload model.