Rewiring central carbon metabolism for tyrosol and salidroside production in Saccharomyces cerevisiae.
Metabolic engineering of Saccharomyces cerevisiae for high-level production of aromatic chemicals has received increasing attention in recent years. Tyrosol production from glucose by S. cerevisiae is considered an environmentally sustainable and safe approach. However, the production of tyrosol and salidroside by engineered S. cerevisiae has been reported to be lower than 2 g/L to date. In this study, S. cerevisiae was engineered with a push-pull-restrain strategy to efficiently produce tyrosol and salidroside from glucose. The biosynthetic pathways of ethanol, phenylalanine, and tryptophan were restrained by disrupting PDC1, PHA2, and TRP3. Subsequently, tyrosol biosynthesis was enhanced with a metabolic pull strategy of introducing PcAAS and EcTyrAM53I/A354V . Moreover, a metabolic push strategy was implemented with the heterologous expression of phosphoketolase (Xfpk), and then erythrose 4-phosphate was synthesized simultaneously by two pathways, the Xfpk-based pathway and the pentose phosphate pathway, in S. cerevisiae. Furthermore, the heterologous expression of Xfpk alone in S. cerevisiae efficiently improved tyrosol production compared with the coexpression of Xfpk and phosphotransacetylase. Finally, the tyrosol yield increased by approximately 135-folds, compared with that of parent strain. The total amount of tyrosol and salidroside with glucose fed-batch fermentation was over 10 g/L and reached levels suitable for large-scale production.


Cave art: an early example of information processing.
This article suggests that ancient cave paintings are evidence of new important brain functions, or "evolutionary software," that facilitated the conceptual and motor processes needed to create a visual scene and render it graphically.


A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth.
The tumor microenvironment plays an important role in the processes of tumor growth, metastasis, and drug resistance. We have used a multilayered 3D primary cell culture model that reproduces the human ovarian cancer metastatic microenvironment to study the effect of the microenvironment on the pharmacological responses of different classes of drugs on cancer cell proliferation. A collection of oncology drugs was screened to identify compounds that inhibited the proliferation of ovarian cancer cells growing as monolayers or forming spheroids, on plastic and on a 3D microenvironment culture model of the omentum metastatic site, and also cells already in preformed spheroids. Target-based analysis of the pharmacological responses revealed that several classes of targets were more efficacious in cancer cells growing in the absence of the metastatic microenvironment, and other target classes were less efficacious in cancer cells in preformed spheres compared to forming spheroid cultures. These findings show that both the cellular context of the tumor microenvironment and cell adhesion mode have an essential role in cancer cell drug resistance. Therefore, it is important to perform screens for new drugs using model systems that more faithfully recapitulate the tissue composition at the site of tumor growth and metastasis.


Efficacy of MRI versus arthroscopy for evaluation of sinus tarsi syndrome.
Magnetic resonance imaging (MRI) has been used to diagnose sinus tarsi syndrome (STS) because of its non-invasiveness and accuracy. The purpose of the present study was to evaluate the diagnostic efficiency of MRI compared with subtalar arthroscopy for STS. Twenty-eight patients (30 feet) who had undergone both MRI and subtalar arthroscopy for STS were evaluated. MRI results were compared with arthroscopic findings, which were considered the standard. Sensitivity, specificity, and positive and negative predictive values were calculated, and correlations between MRI and arthroscopic findings were investigated. MRI was found to detect interosseous talocalcaneal ligament (ITCL) tears, cervical ligament (CL) tears, sinus tarsi fat alterations, and synovial thickening, with sensitivities, specificities, positive and negative predictive accuracies of: 44%, 60%, 85%, 18% (ITCL tears); 73%, 89%, 80%, 86% (CL tears); 71%, 92%, 93%, 71% (sinus tarsi fat alterations); and 86%, 87%, 67%, 95% (synovial thickening). Correlations between MRI and arthroscopic findings showed full agreement in 10%, partial agreement in 50%, and no agreement in 40%. MRI is useful for detecting CL tears, sinus tarsi fat alterations, and synovial thickening, but is inadequate for correctly detecting ITCL tears.


A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression.
Transcriptional repression by nuclear receptors has been correlated to binding of the putative co-repressor, N-CoR. A complex has been identified that contains N-CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3, and which is required for both nuclear receptor- and Mad-dependent repression, but not for repression by transcription factors of the ets-domain family. These data predict that the ligand-induced switch of heterodimeric nuclear receptors from repressor to activator functions involves the exchange of complexes containing histone deacetylases with those that have histone acetylase activity.


Integrative Molecular Characterization of Resistance to Neoadjuvant Chemoradiation in Rectal Cancer.
Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiotherapy (CRT) are incompletely characterized.Experimental Design: We performed integrated whole-exome/transcriptome sequencing and immune infiltrate analysis on rectal adenocarcinoma tumors prior to neoadjuvant CRT (pre-CRT) and at time of resection (post-CRT) in 17 patients [8 complete/partial responders, 9 nonresponders (NR)]. CRT was not associated with increased tumor mutational burden or neoantigen load and did not alter the distribution of established somatic tumor mutations in rectal cancer. Concurrent KRAS/TP53 mutations (KP) associated with NR tumors and were enriched for an epithelial-mesenchymal transition transcriptional program. Furthermore, NR was associated with reduced CD4/CD8 T-cell infiltrates and a post-CRT M2 macrophage phenotype. Absence of any local tumor recurrences, KP/NR status predicted worse progression-free survival, suggesting that local immune escape during or after CRT with specific genomic features contributes to distant progression. Overall, while CRT did not impact genomic profiles, CRT impacted the tumor immune microenvironment, particularly in resistant cases.


HBeAg/anti-HBe seroconversion during and after protracted immunosuppressive treatment in type B chronic hepatitis.
Seventy-seven consecutive HBeAg-positive chronic hepatitis patients were studied from 1971 to 1983 to establish the seroconversion rate in the e system. Patients with less than a year of follow-up were not included in the study. Fifty-six patients with chronic active hepatitis (CAH) received immunosuppressive treatment (corticosteroids combined with azathioprine). The remaining twenty-one patients received no treatment, nine of them with chronic persistent hepatitis (CPH) and 12 with CAH. A retrospective study was performed with stored sera samples: HBeAg and anti-HBe were determined by RIA, and results were correlated with alanine aminotransferase (ALAT) levels in the same samples. The linearized seroconversion rate from HBeAg to anti-HBe was expressed as percent per patient-year. It was 9.6% in CPH patients and 8.8% in CAH patients without treatment. In CAH patients under immunosuppressive drugs it was as low as 1.1% and increased to 28.7% when treatment was withdrawn. ALAT levels were significantly lower in total seroconverted patients when compared with nonseroconverted (NS) patients, but no difference was found between partial seroconverted (PS) and NS patients. The results suggest that although immunosuppressive drug withdrawal may enhance seroconversion rate in type B CAH, delayed seroconversion and reported side effects during treatment stand against protracted usage of these drugs.


Trace Elements in Sea Ducks of the Alaskan Arctic Coast: Patterns of Variation Among Species, Sexes, and Ages.
Climate change and increasing industrialization in the Arctic call for the collection of reference data for assessing changes in contaminant levels. For migratory birds, measuring and interpreting changes in trace element burdens on Arctic breeding areas require insights into factors such as sex, body size, or wintering area that may modify patterns independently of local exposure. In the Alaskan Arctic, we determined levels of trace elements in liver and kidney of common eiders (Somateria mollissima) and long-tailed ducks (Clangula hyemalis) from the Prudhoe Bay oil field and of king eiders (S. spectabilis) and threatened spectacled eiders (S. fischeri) and Steller's eiders (Polystica stelleri) from near the town of Barrow. Small-bodied Steller's eiders and long-tailed ducks from different locations had similarly low levels of selenium (Se), cadmium (Cd), and copper (Cu), perhaps reflecting high mass-specific rates of metabolic depuration during long spring migrations through areas of low exposure. In larger species, Se, Cd, and Cu concentrations were higher in adults than juveniles suggesting that these elements were acquired in nonbreeding marine habitats. Adult male spectacled eiders had exceptionally high Se, Cd, and Cu compared with adult females, possibly because of depuration into eggs and longer female occupancy of nonmarine habitats. Adult female common eiders and juvenile long-tailed ducks at Prudhoe Bay had high and variable levels of Pb, potentially due to local exposure. Explanations for substantial variations in Hg levels were not apparent. Further research into reasons for differing element levels among species and sexes will help clarify the sources, pathways, and risks of exposure.


Evaluation of peripheral nerve regeneration across an 80-mm gap using a polyglycolic acid (PGA)--collagen nerve conduit filled with laminin-soaked collagen sponge in dogs.
We evaluated peripheral nerve regeneration using a novel artificial nerve conduit. The conduit was made of a polyglycolic acid(PGA) - collagen tube filled with laminin- soaked collagen sponge. We implanted this nerve conduit across an 80mm gap in the peroneal nerve of dogs. Histological observation 12 months after implantation showed numerous unmyelinated and myelinated nerve fibershad regenerated beyond the gap. Neurofilaments were widely observed immunohistochemically in the regenerated nerve segments. These findings indicated that newly regenerated axons had extended across the gap and connected into the distal nerve segments. Compound muscle action potentials(CMAPs) and somatosensory evoked potentials (SEPs) were recorded in all dogs. At 12 months, the CMAPs indicated complete recovery, while the SEPs showed incomplete but substantial recovery. Walking patterns had returned to near-normal 12 months after implantation. Use of this nerve conduit can lead to peripheral nerve elongation and favorable functional recovery across a wider nerve gap.


The glycolipids of Lactobacillus casei A.T.C.C. 7469.
1. The lipids were extracted from Lactobacillus casei A.T.C.C. 7469 with chloroform-methanol mixtures. The glycolipids were obtained by chromatography on silicic acid and DEAE-cellulose (acetate form). 2. Hydrolysis of the glycolipids with alkali gave two glycerol glycosides and a mixture of fatty acids. 3. The glycosides were separated and their structures elucidated. The major component was O-alpha-d-galactopyranosyl-(1-->2)-O-alpha-d-glucopyranosyl-(1-->1)-glycerol and the minor component O-alpha-d-glucopyranosyl-(1-->6)-O-alpha-d-galactopyranosyl-(1-->2)-O-alpha-d-glucopyranosyl-(1-->1)-glycerol. 4. Analysis of the fatty acids by gas-liquid chromatography showed that they were predominantly palmitic acid, octadecenoic acid and lactobacillic acid.


Fully Automated Sample Preparation for Ultrafast N-Glycosylation Analysis of Antibody Therapeutics.
There is a growing demand in the biopharmaceutical industry for high-throughput, large-scale N-glycosylation profiling of therapeutic antibodies in all phases of product development, but especially during clone selection when hundreds of samples should be analyzed in a short period of time to assure their glycosylation-based biological activity. Our group has recently developed a magnetic bead-based protocol for N-glycosylation analysis of glycoproteins to alleviate the hard-to-automate centrifugation and vacuum-centrifugation steps of the currently used protocols. Glycan release, fluorophore labeling, and cleanup were all optimized, resulting in a <4 h magnetic bead-based process with excellent yield and good repeatability. This article demonstrates the next level of this work by automating all steps of the optimized magnetic bead-based protocol from endoglycosidase digestion, through fluorophore labeling and cleanup with high-throughput sample processing in 96-well plate format, using an automated laboratory workstation. Capillary electrophoresis analysis of the fluorophore-labeled glycans was also optimized for rapid (<3 min) separation to accommodate the high-throughput processing of the automated sample preparation workflow. Ultrafast N-glycosylation analyses of several commercially relevant antibody therapeutics are also shown and compared to their biosimilar counterparts, addressing the biological significance of the differences.


Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages.
Accumulated evidence suggests that M2-like polarized tumor associated macrophages (TAMs) plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-like TAMs as an appealing target for therapy intervention. Here we found that metformin significantly suppressed IL-13 induced M2-like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-like macrophages promoted migration of cancer cells and endothelial cells. Metformin triggered AMPKα1 activation in macrophage and silencing of AMPKα1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization. Administration of AICAR, another activator of AMPK, also blocked the M2-like polarization of macrophages. Metformin greatly reduced the number of metastases of Lewis lung cancer without affecting tumor growth. In tumor tissues, the percentage of M2-like macrophage was decreased and the area of pericyte-coated vessels was increased. Further, the anti-metastatic effect of metformin was abolished when the animals were treated with macrophages eliminating agent clodronate liposome. These findings suggest that metformin is able to block the M2-like polarization of macrophages partially through AMPKα1, which plays an important role in metformin inhibited metastasis of Lewis lung cancer.


Case Report: Omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in an adolescent patient.
Omadacycline is a novel tetracycline antibiotic that exhibits good in vitro antibacterial activity against atypical pathogens such as Mycoplasma pneumoniae. It is approved for the treatment of adults with community-acquired bacterial pneumonia. However, the safety and efficacy of omadacycline in pediatric patients under 18 years of age have not yet been established. In the present paper, we report a case of pediatric community-acquired pneumonia in which initial empirical anti-infective therapy had failed. The patient received empirical anti-infective therapy with azithromycin and other antimicrobial agents upon admission but showed a poor clinical response and developed secondary tinnitus and liver dysfunction. After the confirmation of M. pneumoniae infection through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, an antibiotic switch to omadacycline was made. Thereafter, the patient's condition improved, and no adverse reactions were observed. These findings demonstrate that mNGS enables the identification of infection-causing pathogens in patients with unresponsive pneumonia. Omadacycline can be considered as an alternative option for anti-infective therapy in pediatric M. pneumoniae pneumonia, especially when the presence of bacterial resistance, adverse drug reactions, or organ failure are taken into consideration.


Femtosecond laser microdissection for isolation of regenerating C. elegans neurons for single-cell RNA sequencing.
Our understanding of nerve regeneration can be enhanced by delineating its underlying molecular activities at single-neuron resolution in model organisms such as Caenorhabditis elegans. Existing cell isolation techniques cannot isolate neurons with specific regeneration phenotypes from C. elegans. We present femtosecond laser microdissection (fs-LM), a single-cell isolation method that dissects specific cells directly from living tissue by leveraging the micrometer-scale precision of fs-laser ablation. We show that fs-LM facilitates sensitive and specific gene expression profiling by single-cell RNA sequencing (scRNA-seq), while mitigating the stress-related transcriptional artifacts induced by tissue dissociation. scRNA-seq of fs-LM isolated regenerating neurons revealed transcriptional programs that are correlated with either successful or failed regeneration in wild-type and dlk-1 (0) animals, respectively. This method also allowed studying heterogeneity displayed by the same type of neuron and found gene modules with expression patterns correlated with axon regrowth rate. Our results establish fs-LM as a spatially resolved single-cell isolation method for phenotype-to-genotype mapping.


CT-guided superior hypogastric plexus block.
This study reports our experience with CT-guided block in the superior hypogastric plexus, using a single needle and anterior approach, in patients with pelvic cancer. Ten patients with pelvic malignancy underwent CT-guided hypogastric neurolytic block with alcohol via an anterior approach. A solution of 10, 15, or 20 ml of alcohol, 4 ml of bupivacaine HCl, and 2 ml of contrast medium was injected. The results were evaluated based on pain relief, using a four-grade analogue scale. CT images always showed spread of solution around the iliac vessels. Pain relief was complete in four cases, moderate in two, mild in three, and none in one. Best results were observed with the largest amounts of alcohol. CT-guided percutaneous superior hypogastric block is a safe, relatively easy, and effective procedure in patients with severe pain from pelvic malignancies.


Enhanced mechanical properties and blood compatibility of PDMS/liquid crystal cross-linked membrane materials.
A novel polydimethylsiloxane/liquid crystal cross-linked membrane (PDMS/LC) was prepared by using PDMS containing vinyl groups and LCs containing unsaturated linkages as matrix materials. Mechanical properties, liquid crystalline performance and blood compatibility of the PDMS/LC cross-linked membrane containing different LC contents and LC groups were investigated, respectively. The results showed that mechanical properties of the membrane increased more significantly than those of pure PDMS membranes. The PDMS/LC cross-linked membrane also possessed better membrane-forming ability, lower hemolysis rate, less platelets adhesion and more favorable anti-coagulant properties. Additionally, mechanical properties and blood compatibility of the membrane can be enhanced simultaneously and obviously due to the introduction of the cholesteric liquid crystals and the application of the preferred cross-linked reaction without byproducts.


Biophysical model of bacterial cell interactions with nanopatterned cicada wing surfaces.
The nanopattern on the surface of Clanger cicada (Psaltoda claripennis) wings represents the first example of a new class of biomaterials that can kill bacteria on contact based solely on their physical surface structure. The wings provide a model for the development of novel functional surfaces that possess an increased resistance to bacterial contamination and infection. We propose a biophysical model of the interactions between bacterial cells and cicada wing surface structures, and show that mechanical properties, in particular cell rigidity, are key factors in determining bacterial resistance/sensitivity to the bactericidal nature of the wing surface. We confirmed this experimentally by decreasing the rigidity of surface-resistant strains through microwave irradiation of the cells, which renders them susceptible to the wing effects. Our findings demonstrate the potential benefits of incorporating cicada wing nanopatterns into the design of antibacterial nanomaterials.


Health and aging.
Regular meditation is the key to health (mental, physical and social wellbeing). It elevates mind from gross level to finer aspect and makes the body and mind follow the law of nature achieving good health, preventing disease, improving performance and reducing aging process. Balanced diet (less sugar, less salt and less fat as age advances supplemented with vitamins and minerals) and mild to moderate exercise (walking etc.) are complimentary to the effects of meditation.


Suppression of CaMKIIβ Inhibits ANO1-Mediated Glioblastoma Progression.
ANO1, a Ca2+-activated chloride channel, is highly expressed in glioblastoma cells and its surface expression is involved in their migration and invasion. However, the regulation of ANO1 surface expression in glioblastoma cells is largely unknown. In this study, we found that Ca2+/Calmodulin-dependent protein kinase II (CaMKII) β specifically enhances the surface expression and channel activity of ANO1 in U251 glioblastoma cells. When KN-93, a CaMKII inhibitor, was used to treat U251 cells, the surface expression and channel activity of ANO1 were significantly reduced. Only CaMKIIβ, among the four CaMKII isoforms, increased the surface expression and channel activity of ANO1 in a heterologous expression system. Additionally, gene silencing of CaMKIIβ suppressed the surface expression and channel activity of ANO1 in U251 cells. Moreover, gene silencing of CaMKIIβ or ANO1 prominently reduced the migration and invasion of U251 and U87 MG glioblastoma cells. We thus conclude that CaMKIIβ plays a specific role in the surface expression of ANO1 and in the ANO1-mediated tumorigenic properties of glioblastoma cells, such as migration and invasion.


The "lung shift" in treated schistosomiasis. Bronchoalveolar lavage evidence of eosinophilic pneumonia.
There is conflicting and incomplete information in the literature on the pulmonary reaction which can occur following treatment of schistosomiasis. We examined the pulmonary function, bronchoalveolar lavage profile, and lung histopathology of a patient with pneumonia and peripheral eosinophilia following oxaminquine chemotherapy for intestinal Schistosoma mansoni infection. Spirometry revealed restrictive rather than obstructive impairment, and lavage showed eosinophil prominence which was also seen in the interstitial and alveolar-filling process in transbronchial biopsies.


Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell.
In cancer metastasis, various environmental stressors attack the disseminating cells. The successful colonization of cancer cells in secondary sites therefore requires the ability of the cells to avoid the consequences of such exposure to the stressors. Here we show that orthotopic transplantation of a CD44 variant isoform-expressing (CD44v(+)) subpopulation of 4T1 breast cancer cells, but not that of a CD44v(-) subpopulation, in mice results in efficient lung metastasis accompanied by expansion of stem-like cancer cells. Such metastasis is dependent on the activity of the cystine transporter xCT, and the stability of this protein is controlled by CD44v. We find that epithelial splicing regulatory protein 1 regulates the expression of CD44v, and knockdown of epithelial splicing regulatory protein 1 in CD44v(+) cells results in an isoform switch from CD44v to CD44 standard (CD44s), leading to reduced cell surface expression of xCT and suppression of lung colonization. The epithelial splicing regulatory protein 1-CD44v-xCT axis is thus a potential therapeutic target for the prevention of metastasis.


Unusual Presentation of Pediatric Scurvy: A Necrotic Gastrostomy Tube Site in a 14-Year-Old Boy.
BACKGROUND Despite being considered a disease of the past, pediatric scurvy is increasingly reported in developed countries, especially among children with autism spectrum disorder, developmental delays, or a restrictive diet. Pediatric patients typically present with lower extremity pain or refusal to walk. This case study features an atypical presentation of scurvy in a non-ambulatory patient. CASE REPORT A 14-year-old boy with arthrogryposis multiplex congenita displayed a late-stage scurvy symptom: a necrotic gastrostomy tube site, indicative of poor wound healing due to vitamin C deficiency. The usual telltale symptoms of scurvy were camouflaged due to his non-ambulatory status, which may have contributed to a delayed presentation. Nevertheless, a comprehensive clinical evaluation, incorporating diet history, gingival symptoms, petechiae, and characteristic radiological signs, eventually led to the correct diagnosis. Although acute osteomyelitis was initially suspected, it was subsequently ruled out. Upon initiation of vitamin C therapy, the patient's symptoms subsided within a few days, and the necrotic tissue surrounding the gastrostomy tube healed completely within two weeks. CONCLUSIONS The highlighted case underscores the importance of including scurvy in the differential diagnosis for pediatric patients with lower extremity pain without fever. A detailed dietary history focusing on vitamin C intake is crucial during clinical evaluation. Early initiation of vitamin C therapy, when scurvy is suspected, may prevent unnecessary and extensive diagnostic workup for other potential causes, offering timely relief to the patient.


The carbohydrate metabolism signature of lactococcus lactis strain A12 reveals its sourdough ecosystem origin.
Lactococcus lactis subsp. lactis strain A12 was isolated from sourdough. Combined genomic, transcriptomic, and phenotypic analyses were performed to understand its survival capacity in the complex sourdough ecosystem and its role in the microbial community. The genome sequence comparison of strain A12 with strain IL1403 (a derivative of an industrial dairy strain) revealed 78 strain-specific regions representing 23% of the total genome size. Most of the strain-specific genes were involved in carbohydrate metabolism and are potentially required for its persistence in sourdough. Phenotype microarray, growth tests, and analysis of glycoside hydrolase content showed that strain A12 fermented plant-derived carbohydrates, such as arabinose and α-galactosides. Strain A12 exhibited specific growth rates on raffinose that were as high as they were on glucose and was able to release sucrose and galactose outside the cell, providing soluble carbohydrates for sourdough microflora. Transcriptomic analysis identified genes specifically induced during growth on raffinose and arabinose and reveals an alternative pathway for raffinose assimilation to that used by other lactococci.


Three ipsilateral paracondylar processes with other skull base variations: case report.
Variations of the skull base can affect surgical approaches and must be considered when viewing and interpreting radiological imaging. Here, we report a unique collection of bony anatomical variations found on a single adult skull. Three bony excrescences from the occipital bone were identified in the paracondylar region. The smallest of these processes was 7 mm long and was just medial to the mastoid process of the temporal bone and posterior to the styloid process. One bony process was attached to the occipital condyle and was 12 mm in length. The longest of these processes was 17 mm long and arose from the jugular process of the occipital bone. Paracondylar processes can be symptomatic. Knowledge of the bony variations at the skull base is important to those who operate in this region or review and interpret radiological imaging.


Microarray Polymer Profiling (MAPP) for High-Throughput Glycan Analysis.
Microarray polymer profiling (MAPP) is a robust and reproducible approach to systematically determine the composition and relative abundance of glycans and glycoconjugates within a variety of biological samples, including plant and algal tissues, food materials, and human, animal, and microbial samples. Microarray technology underpins the efficacy of this method by providing a miniaturized, high-throughput screening platform, allowing thousands of interactions between glycans and highly specific glycan-directed molecular probes to be characterized concomitantly, using only small amounts of analytes. Constituent glycans are chemically and enzymatically fractionated, before being sequentially extracted from the sample and directly immobilized onto nitrocellulose membranes. The glycan composition is determined by the attachment of specific glycan-recognizing molecular probes to the extorted and printed molecules. MAPP is complementary to conventional glycan analysis techniques, such as monosaccharide and linkage analysis and mass spectrometry. However, glycan-recognizing molecular probes provide insight into the structural configurations of glycans, which can aid in elucidating biological interactions and functional roles.


Clear cell basal cell carcinoma with sialomucin deposition.
Clear cell basal cell carcinoma (BCC) is a variant of BCC with a characteristic clear cell component that may occupy all or part of the tumor islands. Periodic acid-Schiff (PAS) staining for glycogen is variably positive, and mild deposition of sulfated mucin has been noted. However, to our knowledge, clear cell BCC with sialomucin deposition has not been reported. Here we report a case of clear cell BCC showing sialomucin deposition. The clear tumor cells stained with PAS and showed incomplete diastase-resistance. In addition, mucin staining with alcian blue was positive at pH 2.5 but not at pH 0.5.


B Cells as an Immune-Regulatory Signature in Ovarian Cancer.
Increasing evidence suggests that the immune system plays a dynamic role in the progression of ovarian cancer, the deadliest gynecological malignancy worldwide. Accumulation of tumor-infiltrating lymphocytes has been associated with increased survival in ovarian cancer patients, and diverse interactions among immune cells in the tumor microenvironment determine tumor progression. While the regulatory functions of T cells among tumor-infiltrating lymphocytes are well defined and also involve therapeutic interventions, the role of B cells in ovarian cancer progression is still limited to their impact on survival. Recent studies have identified both pro- and anti-tumor responses of B cells in solid tumors, as different subsets of B cells play diverse roles in progression. Thus, in-depth characterization of B cell subtypes in each disease stage is crucial for understanding the importance and therapeutic potential of these cells in ovarian cancer. In this review, we summarize current knowledge about B cells in ovarian cancer and discuss emerging therapeutic interventions that could harness B cells to combat this deadly disease.


[Clinical Value of 1.5-T Non-contrast Whole-heart Magnetic Resonance Coronary Angiography in Evaluating the Severity of Coronary Stenosis].
Objective To evaluate the diagnostic performance of 1.5-T non-contrast free-breathing whole-heart magnetic resonance coronary angiography(MRCA)for≥50% and≥70% coronary artery stenosis in coronary artery disease(CAD).Methods Forty-one patients clinically scheduled for invasive coronary angiography(ICA)underwent 1.5-T non-contrast free-breathing whole-heart MRCA.The diagnostic performance for≥50% and≥70% stenosis was evaluated and compared using ICA as a reference standard.Results MRCA was completed in all the 41 patients with the total acquisition time of(10.1 ± 2.2)min.The sensitivity,specificity,and accuracy of MRCA for≥50% and≥70% stenosis were 100%(95% CI:89%-100%)and 82%(95%CI:63%-94%),38%(95%CI:9%-76%)and 54%(95%CI:25%-81%),and 88%(95%CI:73%-95%)and 73%(95%CI:57%-85%)on a per-patient basis,respectively;they were 95%(95%CI:87%-99%)and 86%(95%CI:73%-95%),58%(95%CI:45%-71%)and 76%(95%CI:65%-85%),and 78%(95%CI:69%-84%)and 80%(95%CI:71%-86%)on a per-vessel basis,respectively.The sensitivity of MRCA for≥50% stenosis was higher than that for≥70% stenosis(97%vs.88%,χ 2=5.73,P=0.017),and the specificity showed an opposite trend(86% vs. 94%,χ 2=14.12,P<0.001)on a per-segment basis.Conclusions The 1.5-T non-contrast whole-heart MRCA can detect both≥50% and≥70% coronary artery stenosis with high sensitivity and accuracy.MRCA showed lower sensitivity while higher specificity for≥70% stenosis than for≥50% stenosis on a per-segment basis.


A new approach to the synthesis of trinuclear gold(i) imidazolate complexes and their silver(i)-induced photoluminescence behavior.
New trinuclear gold(i) N-arylimidazolate cluster complexes have been synthesized from cationic [Au(CNR)2]+ isocyanide complexes and their structure and photoluminescence behavior have been compared with those of their 1-methylimidazolate counterpart. A drastic change in their photophysical properties was observed upon coordination of the Ag+ cation.


Genome-wide identification, phylogenetic analysis, expression profiling, and protein-protein interaction properties of TOPLESS gene family members in tomato.
Members of the TOPLESS gene family emerged recently as key players in gene repression in several mechanisms, especially in auxin perception. The TOPLESS genes constitute, in 'higher-plant' genomes, a small multigenic family comprising four to 11 members. In this study, this family was investigated in tomato, a model plant for Solanaceae species and fleshy fruits. Six open reading frames predicted to encode topless-like proteins (SlTPLs) containing the canonical domains (LisH, CTLH, and two WD40 repeats) were identified in the tomato genome. Nuclear localization was confirmed for all members of the SlTPL family with the exception SlTPL6, which localized at the cytoplasm and was excluded from the nucleus. SlTPL genes displayed distinctive expression patterns in different tomato organs, with SlTPL1 showing the highest levels of transcript accumulation in all tissues tested except in ripening fruit where SlTPL3 and SlTPL4 were the most prominently expressed. To gain insight into the specificity of the different TOPLESS paralogues, a protein-protein interaction map between TOPLESS and auxin/indole-3-acetic acid (Aux/IAA) proteins was built using a yeast two-hybrid approach. The PPI map enabled the distinction of two patterns: TOPLESS isoforms interacting with the majority of Aux/IAA, and isoforms with limited capacity for interaction with these protein partners. Interestingly, evolutionary analyses of the TOPLESS gene family revealed that the highly expressed isoforms (SlTPL1, SlTPL3, and SlTPL4) corresponded to the three TPL-related genes undergoing the strongest purifying selection, while the selection was much weaker for SlTPL6, which was expressed at a low level and encoded a protein lacking the capacity to interact with Aux/IAAs.


Promoting effective rehabilitation via nurse-initiated patient transfer.
The transfer of patients from a district general hospital to community hospitals for rehabilitation is a key part of their care. Thorough assessment and preparation of the patient and his or her relatives is essential. Senior nurses in one trust set up a project to improve this transfer process for patients by introducing a nurse-to-nurse referral project.


[Proton spinlocking and T1 rho-weighted MR imaging at 1.5 T].
During spinlocking, the magnetization is aligned along an oscillating field (RF) and relaxes with time constant T1 rho, the spin-lattice relaxation time in the rotating frame. Using a clinical whole-body MR scanner, methods of spinlocking preparation and signal acquisition were combined to evaluate the potential of T1 rho-weighted MR imaging (T1 rho w-MRI) at B0 = 1.5 T. Examinations of the brain of healthy volunteers yielded images with pronounced contrast and T1 rho-variation of the tissue. However, the contrast resembled that of T2-weighted MRI, which is explained by the restricted spinlocking-field strength (BSL < or = 6 microT) on the tomograph. The result (mono-exponential fit) of serial T1 rho w-MRI data from examinations of 8 volunteers was on average 105 +/- 4 ms in the gray matter and 86 +/- 4 ms in the white matter (for BSL = 3 microT). The values are comparable to T2 of both tissues. MRT with spinlocking is less susceptible to local magnetic field inhomogeneities than conventional MRI.


Neurological Complications Secondary to Intimate Partner Violence: A Brief Review and Case of Posterior Cerebral Artery Cerebrovascular Accident Following Domestic Abuse.
Intimate partner violence (IPV) is a growing public health concern, with millions of individuals experiencing IPV each year. Consequences of IPV include psychological disturbances, changes in physical health, and in extreme cases, severe disablement or death. Here, we describe a case of a patient who experienced IPV, leading to a variety of neurological symptoms, and was diagnosed with a posterior cerebral artery (PCA) cerebrovascular accident (CVA) 10 days later. While cases of traumatic brain injury leading to CVA, or stroke, have been documented, there is currently limited reported literature on the neurological complications, specifically stroke, secondary to IPV in adults. Due to this limited reporting, future studies on IPV will be needed to fully understand the long-term neurological complications that may occur.


The effect of hypoxia on the shedding rate of the corneal epithelium.
The reason a cell leaves the corneal epithelial surface at a particular time is not understood. It is likely that a cell must depend on metabolic energy to accomplish this task successfully and with minimal disruption to the epithelial surface and barrier. The hypothesis under test is that the epithelium is directly dependent on atmospheric oxygen to maintain a normal cell shedding rate. Rabbit corneas were excised in pairs and the surfaces bathed with appropriate media for 400 minutes at 304 mOsm/kg and pH 7.4. The epithelial surface of one cornea was bathed with a normoxic solution as a control, while the other cornea was anoxic. Solutions were collected from the epithelial surface at 50 minute intervals. Cell counts of shed corneal epithelial cells were made by staining with acridine orange and viewing with fluorescence microscopy. Stromal thickness was measured at the beginning and at 400 minutes to confirm hypoxia. The results show that hypoxia does reduce the rate at which cells are shed, at least for collections made during the first 50 minutes (P < 0.01). However, by 150 minutes there was no difference between the hypoxic cornea and the control. This result suggests that cell shedding is dependent on oxygen only during the early part of a period of hypoxia. When the hypoxia is prolonged, other mechanisms intervene which preserve the normal shedding rate.


[Impacts of the repetitive transcranial acupuncture stimulation on the content of serum orexin A in patients with post-stroke insomnia].
To compare the effect on post-stroke insomnia between the repetitive transcranial acupuncture stimulation (rTAS) and the conventional western medication in the patients and to explore the mechanism. Ninety patients of post-stroke insomnia were randomized into a rTAS group, a medication group and a placebo group, 30 cases in each one. In the rTAS group, patients were intervened by rTAS. The acupoints were Baihui (GV 20), Ningshen (Extra), emotion area, Wangu (GB 12), Taiyang (EX-HN 5), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Zusanli (ST 36) and Taichong (LR 3). Fast twist with small amplitude was used at Baihui (GV 20) and emotion area for 2-3 min, 200-300 r/min, once 15 min. Electroacupuncture (EA) was applied at Baihui (GV 20) and Ningshen (Extra), bilateral Wangu (GB 12), Sanyinjiao (SP 6) and Zhaohai (KI 6) on the same side, 10 Hz, 0.5-1 mA. The treatment was given for 40 min in the rTAS group, once a day. Diazepam was prescribed orally in the medication group before sleep, 2.5 mg a day. Starch capsule was used in the placebo group before sleep, once a day. All the treatment was given for continuous 1 month. The level of serum orexin A was observed before and after treatment. The effects were compared. The recurrence rate was recorded 3 months after treatment. The total effective rates in the rTAS group and the medication group were 86.7% (26/30) and 90.0% (27/30) repectively after treatment, which were better than 20.0% (6/30) in the placebo group (both P<0.01). After treatment, the levels of serum orexin A in the rTAS group and the medication group were lower than those before treatment (both P<0.01), which were lower than that in the placebo group after treatment (both P<0.01), without statistical significance between the rTAS group and the medication group after treatment (P>0.05). The total effective rates in the rTAS group and the medication group were 86.7% (26/30) and 86.7% (26/30) at follow-up repectively, which were better than 16.7% (5/30) in the placebo group (both P<0.01). The rTAS is safe and effective for post-stroke insomnia, which is similar to oral medication of diazepam. The decreasing serum orexin A may be one of the mechanisms.


Early Venous Occlusion Detection in a Free Flap Using Real-time Laser Doppler Imaging.
Early detection of venous occlusion in free flaps is particularly difficult to identify, and its duration is known to be directly proportional to flap mortality. Here, we report a case of deep inferior epigastric perforator based breast reconstruction in which the intraoperative use of a perfusion camera enabled identifying a venous occlusion based on microcirculatory pulsation dynamics in real time. The sensitivity of our proposed method suggests that in certain cases in which the onset of venous occlusion begins in the operating room we can detect and treat occlusion before sending the patient to recovery. Further development of this technique will allow for earlier and more objective decision making with regard to venous occlusion detection in free tissue transfer.


Neonatal hypocalcemic seizures: case report and literature review.
Seizures during the neonatal period have a broad differential diagnosis, many with a specific treatment and prognosis. In the case reported, a combination of dietary and endocrinologic abnormalities resulted in hypocalcemic seizures, which continued despite aggressive correction of serum ionized calcium levels. Serial electroencephalograms (EEG) performed during the hospitalization were markedly abnormal, and treatment with anticonvulsant drugs was considered given the persistence of seizures despite normalization of serum calcium levels. After 4 days of intravenous calcium administration, the seizure activity resolved, and the patient returned to his normal baseline level of functioning. This case highlights the clinical course of neonatal hypocalcemic seizures, EEG findings in several cases, and possible mechanisms for both hypocalcemic precipitation of seizures and anticonvulsant ineffectiveness.


[Microbial nucleic acids in the pathogenesis of glomerulonephritis].
Recent advances in the understanding of innate pathogen recognition revealed that nucleic acids have immunomodulatory functions in inflammation. A set of Toll-like pattern-recognition receptors recognize various types of microbial nucleic acids, i.e. double-stranded viral RNA (TLR3), single-stranded viral RNA (TLR7 and TLR8), and viral and bacterial CpG-DNA (TLR9). All of these TLRs are differentially expressed in the healthy and diseased kidney and TLR ligation was shown to initiate and modulate experimental glomerulonephritis. In this review we summarize the arising evidence in this field and discuss new hypotheses for the pathogenesis of kidney diseases that are triggered by infectious organisms.


Effect of side-stream phosphorus recovery on biological phosphorus removal performance investigated by chemical and microbial analyses in a novel BNR-IC process.
The aim of this study was to assess the effect of side-stream ratio (SSR) on performance of phosphorus (P) removal and recovery in a novel process linking biological nutrients removal (BNR) and induced crystallization (IC). Results showed that P removal efficiency was significantly enhanced when given an appropriate SSR, resulting in effluent P concentrations decreasing from 0.75 to 0.39 mg/L with an increase of SSR from 0 to 35%, where a maximum of 7.19 mg/L P recovery amount was obtained at 35% of SSR. Increasing the SSR can favor the P recovery, while an excessively high SSR (more than 35%) would have a negative effect on the subsequent biological P removal in the BNR-IC system. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis showed that in total, 11 DGGE bands of highest species richness were visually detected and significant changes in microbial community structure were found, with SSR variations ranging from 0 to 55%. Moreover, an increase in SSR can cause an increase in microbial community biodiversity; where microbial populations correspond to the 11 bands, they were generally classified into five different phyla or classes (Beta-, Gamma-, and Deltaproteobacteria, as well as Clostridia and Flavobacteria) based on the evolutionary tree analysis.


Monoclonal antibodies against different epitopes of peptide hormones. Use of photoreactive analogues in studies on vasopressin.
In order to produce monoclonal antibodies directed against different epitopes of the neurohypophyseal hormone vasopressin, the hormone was coupled to carrier proteins via photoreactive groups at different positions in the vasopressin sequence: [2-(4-azidophenylalanine), 8-arginine]vasopressin (peptide P1, photoreactive group at position 2) and desamino-[8-N6-(4-azidophenylamidino)lysine]vasopressin (peptide P2, photoreactive group at position 8) were conjugated to thyroglobulin by flash photolysis. Monoclonal antibodies against these conjugates bound ([3H]8-arginine]vasopressin with dissociation constants ranging over 40-400 nM. Epitope analysis by means of competitive ELISA showed that the monoclonal antibody obtained with peptide P1 as hapten was directed against the C-terminal acyclic tripeptide when its conformation was stabilized by interaction with the disulphide-linked cyclic hexapeptide. In contrast, the epitope analysis of three monoclonal anti-(peptide P2) antibodies demonstrated that they recognized antigenic determinants in the cyclic hexapeptide ring, mainly the hydrophobic surface formed by Tyr2 and Phe3. Our results suggest that monoclonal antibodies against different epitopes in small peptide hormones can be generated selectively by using photoreactive peptides in such a way that different antigenic sites are exposed in the hapten-carrier conjugate.


Risk stratification of decompensated cirrhosis patients by Chronic Liver Failure Consortium scores: Classification and regression tree analysis.
Decompensated cirrhosis patients have greatly variable prognosis. The aim of the study was to carry out a risk stratification for those patients by Chronic Liver Failure (CLIF) Consortium scores. The performance of CLIF Consortium acute-on-chronic liver failure scores (CLIF-C ACLFs) and CLIF Consortium Acute Decompensation scores (CLIF-C ADs) were validated in 209 patients with ACLF and 1245 patients without ACLF at admission from the Ningbo Cohort. A classification and regression tree (CRT) analysis by CLIF-C ACLFs/CLIF-C ADs was carried out to stratify death risk among patients. The CLIF-C ACLFs and CLIF-C ADs showed higher predictive accuracy than Model for End-stage Liver Disease (MELD) scores, MELD plus serum sodium (MELD-Na) scores, and Child-Turcotte-Pugh classification (CP) at main time points (28, 90, 180, and 365 days), determined by area under the receiver-operating characteristic curve and concordance index in ACLF and no-ACLF patients at admission. The CRT analysis categorized ACLF patients into two groups (advanced and early ACLF), and no-ACLF patients into three groups (high-, medium-, and low-risk AD) according to risk of death. However, early ACLF and high-risk AD patients had comparable mortality at the main time points. The CRT model had a higher area under the receiver-operating characteristic curve than MELDs, MELD-Nas, and CPs in predicting prognosis in all patients. The CLIF-C ACLF and CLIF-C AD are better prognostic scores than MELD, MELD-Na, and CP in predicting mortality of ACLF and no-ACLF patients. A combined use of CLIF- Sequential Organ Failure Assessment, CLIF-C ACLFs, and CLIF-C ADs could identify cirrhosis patients at high death risk and assist clinical decisions for management.


Withdrawal of antipsychotic drugs from adults with intellectual disabilities.
There is a view that antipsychotic drugs can be successfully withdrawn from people with intellectual disabilities with resultant health gain. This study critically examines whether antipsychotic drug withdrawal is beneficial. 119 adults with intellectual disabilities were included in a programme of antipsychotic drug withdrawal. The clinical outcomes of this programme are poor. Only 7.6% completely withdrew from antipsychotic drugs, and 48.7% experienced onset/deterioration in problem behaviours or mental ill-health. Significant drug side effects with the introduction of new drugs were experienced by 23.3%. Resultant mean antipsychotic drug doses were higher compared with those at the start of the programme. The cost to the intellectual disabilities psychiatric service (over and above that of routine psychiatric care) was £258,050 (€391,693), and the human cost was considered high. Primary care, social care and family costs were not calculated. The only specific factors found to be associated with poor outcome were increased severity of intellectual disabilities and female gender. The successful role of antipsychotic drugs in the management of problem behaviours in people who do not have verbal communication skills may relate to the pathoplastic effect of intellectual disabilities on clinical presentation, with problem behaviours being markers of eg. psychosis and anxiety disorders. Our original findings challenge the view that routine withdrawal of antipsychotic drugs is good practice; we reinterpret the existing literature, and recommend caution and vigilance in pharmacotherapy.


Precision of the iDXA for visceral adipose tissue measurement in severely obese patients.
A new measurement tool, the automated software CoreScan, for the GE Lunar iDXA, has been validated for measuring visceral adipose tissue (VAT) against computed tomography in normal-weight populations. However, no study has evaluated the precision of CoreScan in measuring VAT among severely obese patients. The purpose of the study was to evaluate the precision of CoreScan for VAT measurements in severely obese adults (body mass index > 40 kg·m(-2)). A total of 55 obese participants with a mean age of 46 ± 11 yr, body mass index of 49 ± 6 kg·m(-2), and body mass of 137.3 ± 21.3 kg took part in this study. Two consecutive iDXA scans with repositioning of the total body were conducted for each participant. The coefficient of variation, the root-mean-square averages of SD of repeated measurements, the corresponding 95% least significant change, and intraclass correlations were calculated. Precision error was 8.77% (percent coefficient of variation), with a root-mean-square SD of 0.294 kg and an intraclass correlation of 0.96. Bland-Altman plots demonstrated a mean precision bias of -0.08 ± 0.41 kg, giving a coefficient of repeatability of 0.82 kg and a bias range of -0.890 to 0.725 kg. When interpreting VAT results with the iDXA in severely obese populations, clinicians should be aware of the precision error for this important clinical parameter.


CD4 T lymphocyte activation in acute severe asthma.
The expression of activation molecules on peripheral-blood CD4 and CD8 T lymphocytes and the serum concentrations of two products of activated T lymphocytes [interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R)] were measured in patients with acute severe asthma (ASA) and controls. Significantly higher percentages of CD4+ cells from patients with ASA expressed IL-2R, HLA-DR and VLA-1 as compared to controls (p less than 0.01). In contrast, CD8+ cells from both asthmatics and controls did not express IL-2R and VLA-1, and their expression of HLA-DR in asthmatics was not increased. Serum concentrations of IFN-gamma and sIL-2R were significantly elevated in patients with ASA as compared to control groups (p less than 0.01). Concentrations decreased as the patients improved clinically following therapy. Significant correlations were observed between the improvements in airways obstruction and (1) the decreases in the percentages of peripheral-blood IL-2R+ T lymphocytes and (2) the decreases in serum concentrations of sIL-2R. These observations suggest that CD4 T lymphocyte activation is important in the pathogenesis of ASA.


Identification of actin microfilaments in the intracytoplasmic inclusions present in recurring infantile digital fibromatosis (Reye tumor).
The diagnostic intracytoplasmic perinuclear inclusion bodies within the fibroblastic tumor cells of recurring digital fibrous tumor of childhood (Reye tumor) were found to be ultrastructurally composed of condensed microfilaments that were continuous with axially oriented cytoplasmic filament bundles running toward the cell membrane. Immunofluorescence microscopy performed with antibodies raised against vimentin and against actin revealed a strong positive reaction for vimentin in the tumor cell cytoplasm, whereas the spherical inclusion bodies were actin-positive. From these results the following conclusions may be drawn: (I) the mesenchymal origin of the Reye tumor cells is consistent with the identification of vimentin intermediate filaments and (II) the actin-positive spherical inclusion bodies appear to represent pathological aggregations of microfilaments.


Hyperbranched polyphosphates for drug delivery application: design, synthesis, and in vitro evaluation.
A water-soluble hyperbranched polyphosphate (HPHEEP) was synthesized through the self-condensation ring-opening polymerization (SCROP) of 2-(2-hydroxyethoxy)ethoxy-2-oxo-1,3,2-dioxaphospholane (HEEP), and its suitability as a drug carrier was then evaluated in vitro. Methyl tetrazolium (MTT) and live/dead staining assays indicated that HPHEEP had excellent biocompatibility against COS-7 cells. The good biodegradability of HPHEEP was observed by NMR analysis, and the degradation products were nontoxic to COS-7 cells. Flow cytometry and confocal laser scanning microscopy analyses suggested that HPHEEP could be easily internalized by vivid cells and preferentially accumulated in the perinuclear region. Furthermore, a hydrophobic anticancer drug, chlorambucil, was used as a model drug and covalently bound to HPHEEP. The chlorambucil dose of the conjugate and free drug required for 50% cellular growth inhibition were 75 and 50 microg/mL, respectively, according to MTT assay against an MCF-7 breast cancer cell line in vitro. This high activity of the conjugate may be attributed to the biodegradability of HPHEEP so as to release the chlorambucil in cells. Therefore, on the basis of its biocompatibility and biodegradability, HPHEEP could provide a charming opportunity to design some excellent drug delivery systems for therapeutic applications.


Diagnosis of infection of implantable central venous catheters by [18F]fluorodeoxyglucose positron emission tomography.
The aim of this study was to evaluate the role of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the diagnosis of infection of implantable vascular catheters. We evaluated six patients with haematological cancer and infection of their implantable vascular catheter and who underwent FDG PET imaging around the time of their infection. Six patients with multiple myeloma who developed infection of their implantable device (five port pocket infections and one tunnel infection) were identified. FDG PET revealed increased uptake at the site of the implantable catheter (SUV 2.7-4.5) in all six patients, even in the absence of signs or symptoms of infection at the site of the device (three), and the presence of severe neutropenia (four). The three patients who did not have local inflammation at the site of the device were profoundly neutropenic. The FDG PET diagnosis led to removal of the device in two patients. FDG PET is a safe, rapid and accurate tool for diagnosing infection of an implantable catheter, including among those patients not exhibiting local signs and symptoms of infection, and in whom the diagnosis of infected device may be difficult. FDG PET may help prevent the unnecessary removal of implantable intravascular catheters and the unwarranted use of antibiotics.


A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.
We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.


All-solution-processed Si films with broadband and omnidirectional light absorption.
Silicon photonic structures have attracted a great deal of attention due to their potential benefits of efficient light management in optoelectronic applications. In this paper, we demonstrate broadband optical absorption enhancement in solution-processed amorphous silicon (a-Si) by leveraging the advantages of silicon photonic structures. Graded refractive index silicon multi-layer structures are employed by modulating optical constants with simple process optimization, resulting in significantly improved reflectance over a broad range of visible wavelengths. In addition, nanopatterning flexibility of solution-processed silicon provides benefits for tailoring silicon optical properties. With the incorporation of the two-dimensional submicron pattern into silicon films, the absorptivity of silicon films improves considerably below the wavelength of the bandgap (λ ∼ 800 nm), and the limited bandwidth of absorptivity in silicon films can be extended to near-infrared wavelengths by coating with a thin gold layer. The methodology is generally applicable to a platform for improving the broadband optical absorption of photonic and optoelectronic devices.


[Static and dynamic volumes after myocardial infarction/clinical and radiological correlation].
A study was made of pulmonary function tests in patients averaging 2 years post MI, who did not present evidence of chronic bronchitis or other types of primary pneumopathy. The influence of smoking and moderate pulmonary congestion due to heart failure were studied. We found a significant inverse relation between dyspnea and the forced one second expiratory volume, as an expression of bronchial obstruction. There was a significant increase in the respiratory volume in patients after MI. This alteration was particularly evident in patients who smoked. On the contrary, in pulmonary congestion the tendency was towards a decrease in respiratory volume. We confirmed the importance of pulmonary function tests for the evaluation of subjective symptoms, this was confirmed by the finding of a decrease in the dynamic pulmonary volumes, specially in smokers, which demonstrates the unfavorable influence of smoking. Heart failure did not significantly influence static or dynamic parameters, although the residual functional capacity showed a tendency to decrease with the degree of congestion.


Antithymocyte globulin is associated with complement deposition in cardiac transplant biopsies.
Polyclonal antithymocyte globulin preparations contain antibodies with reactivity to endothelial cells. Therefore, we investigated whether treatment with this reagent caused complement deposition in human cardiac transplants. Frozen tissue was available from endomyocardial biopsies of 75 patients, who were transplanted between April 1995 and April 2000. Nine of these patients were converted from cyclosporin A (CsA) to horse antithymocyte globulin (ATGAM) in the first month after transplantation. All of the biopsies were stained by immunofluorescence for C4d as evidence of activation of the classical pathway of complement. In addition, biopsies from patients treated with ATGAM and control patients were stained for deposition of horse immunoglobulin (Ig)G. All nine patients who received ATGAM had deposition of horse IgG and C4d. Two color stains demonstrated that the horse IgG colocalized with the C4d staining. No staining for horse IgG or C4d was evident in biopsies obtained before ATGAM treatment. Likewise, no staining for horse IgG was detected in seven control patients who had C4d staining. Most patients treated with ATGAM had no histologic evidence of rejection, but did have myocyte damage and macrophage infiltration. Thus prophylactic treatment with ATGAM is associated with the deposition of horse IgG and activation of complement in the transplant.


The temperament and character personality profile of the glaucoma patient.
To determine the temperament and character profile of glaucoma patients. A total of 234 patients (104 with primary open angle glaucoma, and 130 control subjects without any ocular disease) were selected for this prospective, cross-sectional study. All the participants underwent a comprehensive ophthalmological examination, including the best corrected visual acuity, intraocular pressure measurement, gonioscopy, and visual field analysis. All the participants were given the Turkish version of the Temperament and Character Inventory (TCI). The TCI is a self-reported evaluate, with 240 true/false items measuring four domains of temperament; harm avoidance (HA), persistence (PS), novelty seeking (NS), reward dependence (RD), and three domains of character; self-transcendence (ST), cooperativeness (C), self-directedness (SD). The glaucoma patients achieved the higher scores than the controls for the HA and SD dimensions (p < 0.001 and p = 0.033). The glaucoma patients scored lower than the controls for the NS, P and ST dimensions (p < 0.001, p < 0.001 and p = 0.002). There were no differences in the RD and C scores between the patients and the controls (p = 0.944 and p = 0.343). There was no correlation between the duration of illness and the TCI dimensions. Disease severity was positively associated with HA (r = 0,220, p = 0,025) and the anticipatory worry (r = 0.227, p = 0.021) dimension. Glaucoma patients had a different personality profile to healthy individuals. This may affect treatment compliance and is also important when coping with maladaptive patient attitudes.


Toxicity of Bacillus thuringiensis Cry2Ab and the inheritance of Cry2Ab resistance in the Pink bollworm, Pectinophora gossypiella (Saunders).
Though the insecticidal crystal (Cry) proteins produced by Bacillus thuringiensis (Bt) are effective against insect pests, evolution of resistance remains an issue of great concern. Here, we explored the ability of pink bollworm, Pectinophora gossypiella (Lepidoptera: Gelechiidae), a key pest of cotton, to evolve resistance to Cry2Ab and characterized it in terms of inheritance. Sixteen day bioassay of Bt Cry2Ab toxin against 5-day old pink bollworm larvae showed median lethal concentration (LC(50)) ranging 0.16-1.44 µg/g diet for five different populations collected from Srivilliputtur (Tamil Nadu), Jalgaon (Maharashtra), Bharuch (Gujarat), New Delhi (Delhi) and Sri Ganganagar (Rajasthan). Selection of pink bollworm for evolution of Cry2Ab resistance led to the maximal of 37.75-fold resistance vis-à-vis the most susceptible strain. Further studies on inheritance using above parental populations showed autosomal and semidominant nature of Cry2Ab resistance, with dominance h values of 0.69 and 0.79 for two reciprocal crosses. The inheritance of Cry2Ab resistance appeared to be governed by multiple alleles/genes. Cry2Ab resistance was associated with fitness costs in terms of prolonged larval and pupal period when resistant parent population was reared on the diet without toxin. Fitness cost in terms of larval period appeared to be inherited in F(1), F(2) and backcross progenies. F(2) progeny also inherited these differences in larval and pupal periods. These studies clearly advocate rigorous monitoring of Cry2Ab resistance and compliance of resistance management in the pink bollworm for ensuring Bt cotton sustainability.


Decreased quinolinic acid in the hippocampus of depressive patients: evidence for local anti-inflammatory and neuroprotective responses?
Disturbances of glutamatergic neurotransmission and mononuclear phagocyte system activation have been described uni- and bipolar depression (UD/BD). Linking the glutamate and immune hypotheses of depression, quinolinic acid (QUIN) is synthesized by activated microglia and acts as an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist with neurotoxic properties. Recently, we observed an increased microglial QUIN expression in the subgenual and supracallosal, but not in the pregenual part of the anterior cingulate cortex in postmortem brains of suicide cases with severe depression. Since several hints point to a role of the hippocampus in depression, we extended our study and addressed the question whether microglial QUIN is also changed in subregions of the hippocampus (CA1 and CA2/3 areas) in these patients. Postmortem brains of 12 acutely depressed patients (UD, n = 6; BD, n = 6) and 10 neuropsychiatric healthy age- and gender-matched control subjects were analyzed using QUIN-immunohistochemistry. Hippocampal volumes were determined in order to assess possible neurotoxic or neurodegenerative aspects. Microglial QUIN expression in the whole group of depressed patients was either comparable (left CA1, right CA2/3) or decreased (right CA1: p = 0.004, left CA2/3: p = 0.044) relative to controls. Post hoc tests showed that QUIN was reduced both in UD and BD in the right CA1 field (UD, p = 0.048; BD, p = 0.031). No loss of hippocampal volume was detected. Our data indicate that UD and BD are associated with a local reduction in QUIN-immunoreactive microglia in the hippocampus and underline the importance of the NMDA-R signaling in depressive disorders.


Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus.
Although pruritus is the predominant and commonest feature of atopic dermatitis, its clinical characteristics have not been explored. To characterize the clinical pattern and sensory and affective dimensions of the itch experience utilizing a comprehensive itch questionnaire. A structured itch questionnaire based on the McGill pain questionnaire was given to 102 Chinese patients with known atopic dermatitis. There were 100 patients with atopic dermatitis who fully filled the questionnaire. In 87% of the patients pruritus appeared on a daily basis. It had a prolonged duration (mean duration 10.7 7.3 years). It involved all body areas mostly in the lower limbs (83%), flexures (76%), upper limbs (71%) and neck (65%). Itch intensity during its peak was nearly twice higher than the itch of a mosquito bite. Itching was most frequent at night (65%), and 84% of patients reported of difficulty falling asleep. Daily life activities which increased the severity of itch were sweat in 96%, dryness in 71%, stress in 71% and physical effort in 73%. The major factors which were found to reduce the intensity of pruritus included: bathing with cold water in 55% and cold ambient environment in 56%. Associated symptoms were heat sensation (51%), sweating (40%) and pain in the pruritic area (45%). The various anti-pruritic therapies had limited long-term effect. The pruritus was bothersome (52%) and a major distress to the patient. The affective score correlated to itch intensity during its peak (r = 0.4, P < 0.001). The study provided a detailed description of pruritus in atopic dermatitis with new data on affective and sensory dimensions and associated symptoms. The questionnaire was found to be a useful tool in characterization of itch.


Reconstitution of membrane proteins: sequential incorporation of integral membrane proteins into preformed lipid bilayers.
Several integral membrane proteins can be inserted sequentially into preformed unilamellar vesicles (ULV's) composed of dimyristoylphosphatidylcholine (DMPC) and cholesterol in a gel phase. Thus, proteoliposomes of DMPC, cholesterol, and bacteriorhodopsin from Halobacterium halobium rapidly incorporate UDPglucuronosyltransferase (EC 22.214.171.124) from pig liver microsomes, cytochrome oxidase from beef heart mitochondria, and additional bacteriorhodopsin, added sequentially. This process of spontaneous incorporation can be regulated to produce complex artificial membranes that contain phospholipids and proteins at ratios (mol/mol) equivalent to what is found in biological membranes. The ability of the lipid-protein bilayers to incorporate additional integral membrane proteins is not affected by annealing of the proteoliposomes at 37 degrees C nor by the order of addition of the proteins. Bacteriorhodopsin-containing vesicles formed by the sequential addition of integral membrane proteins demonstrate light-driven proton pumping. Therefore, they have retained a vesicular structure. Vesicles containing one or two different proteins will fuse with each other at 21 degrees C or with ULV's devoid of proteins. Incorporation of bacteriorhodopsin or UDPglucuronosyltransferase into proteoliposomes containing DMPC, with or without cholesterol as impurity, also occurs above the phase transition for DMPC. The presence of a protein in a liquid-crystalline bilayer provides the necessary condition for promoting the spontaneous incorporation of other membrane proteins into preformed bilayers.


Telehealth: Synopsis.
The COVID-19 pandemic has changed the Australian medical landscape, especially in relation to how we need to provide clinical care in general practice.


Anatomical variability of median nerve formation in human foetuses in clinical aspect.
The median nerve is an important nerve leaving the brachial plexus. Median nerve damages may result from tunnel syndromes or injuries. The nerve anatomical variants are of great clinical importance in hand surgery. Clinical evaluation of median nerve divergence from brachial plexus morphological variability in foetal period. The material consisted of 220 brachial plexus sections derived from 110 foetuses aged 14-32 weeks of foetal life (50 females and 60 males, in CRL: 80-233 mm). The survey incorporated the following methods: dissection, anthropological, image digital acquisition, Image J computer transformation system, GIMP programme and statistical methods. Typology assessment was based on 0/1 system. Sexual dimorphism and symmetry were examined. Median nerve left directly lateral cord in 5 cases. In 59 (26.81%) plexuses, anterior division of middle trunk co-created median nerves anomalies. The total of 9 types of anterior division of middle trunk as well as of median nerve were distinguished. Median nerve double root leaving lateral cord was observed in 10 (9.09%) cases, whereas triple lateral root was seen in one case. In 1/3 of the examined plexuses, median nerve roots combined to form the nerve beneath humeral bone head and even in ½ of the bone distal length (type II and III). Type II prevailed more often on the left side. Median nerve roots as well as the median nerve itself are characteristic for significant morphological variability. Nerve roots low junction into median nerve is clinically favourable as it can prevent nerve damage during injuries.


Use of autologous blood as part of the perfusate for cardiopulmonary bypass: a priming technique.
In an attempt to replace the oncotic and protein coating capabilities of serum albumin in the perfusate, we established a priming protocol that used autologous blood as part of the perfusate solution. Prior to March 1, 1999, our standard priming protocol was 1650 ml of crystalloid with 250 ml of 5% serum albumin and 5,000 units of heparin. After removing albumin from our prime, our standard protocol was altered to include 40 ml of the patient's autologous blood in 1,800 ml of crystalloid and 10,000 units of heparin. To determine the intraoperative effects of using albumin/crystalloid primes (Group A), autologous blood/crystalloid primes (Group B) and crystalloid primes (Group C), a total of 178 patients were sequentially evaluated. Intraoperative parameters evaluated were total protein (TP), colloid osmotic pressure (COP), platelets (Plts) and fluid requirements during cardiopulmonary bypass (CPB). During an overlapping 12-month period of time, 1,092 consecutive cardiac surgical cases using CPB (584 albumin prime; 508 autologous blood prime) were evaluated for clinical outcomes in terms of mortality and length of hospitalization. In addition, over a period of 15 months, 1,458 patients in both the autologous blood/crystalloid group and the crystalloid only group were evaluated for the incidence of high-pressure excursions (HPE) after going on bypass. Comparative reviews of TP, COP and Plts demonstrated no significant difference 10 min after the start of bypass between Groups A and B. However, in Group C, there was a statistically significant increase in the intraoperative fluid requirements during CPB, compared to both of the other groups. There was no significant difference in the incidence of HPE, with an occurrence of 1.04% in the crystalloid only group and 1.11% in the autologous blood/crystalloid group. Autologous blood perfusates were identical to albumin perfusates in their platelet protection and reduction of fluid shifts during the intraoperative period.


Identification of antigenically related polypeptides at centrioles and basal bodies.
An antigen localized at the centriolar region has been identified by indirect immunofluorescence studies in African green monkey kidney, human, hamster, rat, and mouse cells. The antigen consists of two polypeptides of 14,000 and 17,000 daltons. A related antigen is also present at the basal body region in ciliated cells from chicken, cat, mouse, pig, steer, and rabbit trachea and from rabbit fimbria. Immunoelectron microscopy shows that the immunoreactive antigen is indeed located in the region around the basal bodies of ciliated cat tracheal cells. Thus, we have found an antigen that is common to a variety of cell types from many different animal sources and is specifically associated with both centrioles and basal bodies. The possible role of the antigen in differentiation is discussed.


The influence of diabetes mellitus on short-term outcomes of patients with bleeding peptic ulcers.
Little information is available on the influence of diabetes mellitus on the short-term clinical outcomes of patients with bleeding peptic ulcers. The aim of this study is to investigate whether diabetes mellitus influences the short-term clinical outcomes of patients with bleeding peptic ulcers using a Japanese national administrative database. A total of 4863 patients treated by endoscopic hemostasis on admission for bleeding peptic ulcers were referred to 586 participating hospitals in Japan. We collected their data to compare the risk-adjusted length of stay (LOS) and in-hospital mortality of patients with and without diabetes mellitus within 30 days. Patients were divided into two groups: patients with diabetes mellitus (n=434) and patients without diabetes mellitus (n=4429). Mean LOS in patients with diabetes mellitus was significantly longer than those without diabetes mellitus (15.8 days vs. 12.5 days, p<0.001). Also, higher in-hospital mortality within 30 days was observed in patients with diabetes mellitus compared with those without diabetes mellitus (2.7% vs. 1.1%, p=0.004). Multiple linear regression analysis revealed that diabetes mellitus was significantly associated with an increase in risk-adjusted LOS. The standardized coefficient was 0.036 days (p=0.01). Furthermore, the analysis revealed that diabetes mellitus significantly increased the risk of in-hospital mortality within 30 days (odds ratio=2.285, 95% CI=1.161-4.497, p=0.017). This study demonstrated that presence of diabetes mellitus significantly influences the short-term clinical outcomes of patients with bleeding peptic ulcers.


Convergence behavior of iterative SENSE reconstruction with non-Cartesian trajectories.
In non-Cartesian SENSE reconstruction based on the conjugate gradient (CG) iteration method, the iteration very often exhibits a "semi-convergence" behavior, which can be characterized as initial convergence toward the exact solution and later divergence. This phenomenon causes difficulties in automatic implementation of this reconstruction strategy. In this study, the convergence behavior of the iterative SENSE reconstruction is analyzed based on the mathematical principle of the CG method. It is revealed that the semi-convergence behavior is caused by the ill-conditioning of the underlying generalized encoding matrix (GEM) and the intrinsic regularization effect of CG iteration. From the perspective of regularization, each iteration vector is a regularized solution and the number of iterations plays the role of the regularization parameter. Therefore, the iteration count controls the compromise between the SNR and the residual aliasing artifact. Based on this theory, suggestions with respect to the stopping rule for well-behaved reconstructions are provided. Simulated radial imaging and in vivo spiral imaging are performed to demonstrate the theoretical analysis on the semi-convergence phenomenon and the stopping criterion. The dependence of convergence behavior on the undersampling rate and the noise level in samples is also qualitatively investigated.


Factors affecting survival of uncemented total hip arthroplasty in patients 50 years or younger.
Providing a long-lasting total hip arthroplasty for patients younger than 50 years remains one of the greatest challenges for modern arthroplasty surgery. We retrospectively reviewed 221 patients younger than 50 years who underwent 299 uncemented total hip arthroplasties from 1983 to 2000. We assessed 5- to 15-year survival with revision as the endpoint. Femoral stem survival was 99.3% (range, 98.4-100%), 98.9% (range, 97.7-100%), and 96.8% (92.5-100%) at 5, 10, and 15 years, respectively. Including all component designs acetabular survival was 98.7% (range, 97.4-100%), 84.6% (78.8-90.4%), and 52.5% (40.7-64.3%) at 5, 10, and 15 years, respectively. Overall survival was 46.8% (33.5-58.1%) at 15 years. Total hip arthroplasties performed for hip dysplasia had lower 10-year and 15-year survival. Zirconium-on-polyethylene articulations had lower acetabular revision rates compared with cobalt-chrome-on-polyethylene. Sixty-nine revisions were performed, most commonly for polyethylene wear. Uncemented femoral stems resulted in 90% survival at 15 years followup in patients younger than 50 years at index operation. Contemporary bearing surfaces in association with such stems may provide long-lasting total hip arthroplasties, even in young, active patients.


Acute arthritis of the right temporomandibular joint due to Lyme disease: a case report and literature review.
Lyme disease is the most frequent tick-borne infectious disease in Europe. It often presents with a wide variety of symptoms. For this reason, affection of the temporomandibular joint (TMJ) caused by Lyme disease (LD) can be misdiagnosed as a common temporomandibular disorder (TMD). The purpose of this case report of a 25-year-old woman presenting to the Departments of Orthodontics and Oral and Maxillofacial Surgery with extensive symptoms of temporomandibular disorder is to illustrate the delayed diagnosis of Lyme disease which was only made after extensive therapy of the temporomandibular joint. The specialist literature only reports a few cases of patients suffering from Lyme disease with TMJ manifestations. This case report and the relevant literature review aim to emphasize the importance of accurate request of medical history and differential diagnosis of acute TMJ arthritis and arthralgia. Early interdisciplinary diagnosis of Lyme disease and early antibiotic therapy are essential to avoid misdiagnosis and unnecessary, sometimes invasive, therapies.


Menaquinone-7 production from maize meal hydrolysate by Bacillus isolates with diphenylamine and analogue resistance.
A menaquinone-7 (MK-7) high-producing strain needs to be isolated to increase MK-7 production, in order to meet a requirement of MK-7 given the low MK-7 content in food products. This article focuses on developing MK-7 high-producing strains via screening and mutagenesis by an atmospheric and room temperature plasma (ARTP) mutation breeding system. We isolated an MK-7-producing strain Y-2 and identified it as Bacillus amyloliquefaciens, which produced (7.1±0.5) mg/L of MK-7 with maize meal hydrolysate as carbon source. Then, an MK-7 high-producing strain B. amyloliquefaciens H.β.D.R.-5 with resistance to 1-hydroxy-2-naphthoic acid, β-2-thienylalanine, and diphenylamine was obtained from the mutation of the strain Y-2 using an ARTP mutation breeding system. Using strain H.β.D.R.-5, efficient production of MK-7 was achieved ((30.2±2.7) mg/L). In addition, the effects of nitrogen sources, prenyl alcohols, and MgSO4 on MK-7 production were investigated, suggesting that soymeal extract combined with yeast extract, isopentenol, and MgSO4 was beneficial. Under the optimized condition, the MK-7 production and biomass-specific yield reached (61.3±5.2) mg/L and 2.59 mg/L per OD600 unit respectively in a 7-L fermenter. These results demonstrated that strain H.β.D.R.-5 has the capacity to produce MK-7 from maize meal hydrolysate, which could reduce the substrate cost.


Molecular Signatures of JMJD10/MINA53 in Gastric Cancer.
The JMJD10 gene and its encoded protein MYC-induced nuclear antigen (MINA53) are associated with multiple cancers. Besides having both an oncogenic and tumor suppressor function, the intricate role of JMJD10 in cancer is complex as it depends on the cancer type. In particular, the functional role of JMJD10/MINA53 in gastric cancer has been poorly understood. In this study, we have unraveled the molecular signatures and functional roles of JMJD10/MINA53 in gastric cancer by multiple approaches, i.e., multi-omics bioinformatics study, analysis of human gastric cancer tissues, and studies in vitro using knockdown or overexpression strategies in gastric cancer cell lines. The results indicated that the JMJD10 gene and MINA53 protein are commonly overexpressed in cancer patients. JMJD10/MINA53 is involved in the regulation of proliferation and survival of gastric cancer by controlling cell cycle gene expression. These processes are highly associated with MINA53 enzymatic activity in the regulation of H3K9me3 methylation status and controlling activation of AP-1 signaling pathways. This highlights the oncogenic role of JMJD10/MINA53 in gastric cancer and opens the opportunity to develop therapeutic targeting of JMJD10/MINA53 in gastric cancer.


Exposure to gamma-irradiation increases phorbol myristate acetate-induced H2O2 production in human macrophages.
Cell number, protein, and phorbol myristate acetate (PMA)-induced H2O2 production were measured in cultured human peripheral blood monocytes for six days after exposure to varying doses of gamma-radiation. Both the number of adherent cells and the protein per dish decreased with increasing radiation doses. The dose of radiation decreasing the number of adherent cells by 37% on days 4 and 6 postirradiation was 29 Gy. Four hours postirradiation there was a small decrease in PMA-induced H2O2 production for doses of 7.5 Gy or greater; levels returned to normal by eight hours and increased at 24 hours postirradiation. By day 4 postirradiation significant increases in PMA-induced H2O2 production were noted at all radiation doses (2.5 to 50 Gy). This increase was not due to a shift in the PMA dose-response curve, a change in the time course of the PMA response, or an effect of decreased cell density on the assay system. Superoxide levels were not significantly changed in cells exposed to 20 Gy. Catalase, glutathione peroxidase, and superoxide dismutase levels also were unchanged. Culturing irradiated cells with gamma-interferon increased PMA-induced H2O2 release, which indicated that irradiated cells retained their capacity to respond to gamma-interferon. These data demonstrate that irradiation affects the PMA-induced H2O2 production of human monocytes in a time- and dose-dependent manner. An increase in the release of reactive oxygen intermediates by the macrophage may play a role in enhancing the deleterious effects of radiation in vivo.


2-Iminohomopiperidinium salts as selective inhibitors of inducible nitric oxide synthase (iNOS).
An attractive approach to the treatment of inflammatory conditions such as osteo- and rheumatoid arthritis, inflammatory bowel disease, and sepsis is through the selective inhibition of human inducible nitric oxide synthase (hiNOS) since localized excess nitric oxide (NO) release has been implicated in the pathology of these diseases. A series of monosubstituted iminohomopiperidinium salts possessing lipophilic functionality at ring positions 3, 5, 6, and 7 has been synthesized, and series members have demonstrated the ability to inhibit the hiNOS isoform with an IC50 as low as 160 nM (7). Compounds were found that selectively inhibit hiNOS over the human endothelial constitutive enzyme (heNOS) with a heNOS/hiNOS IC50 ratio in excess of 100 and as high as 314 (9). Potencies for inhibition of hiNOS and the human neuronal constitutive enzyme (hnNOS) are comparable. Substitution in the 3 and 7 positions provides compounds that exhibit the greatest degree of selectivity for hiNOS and hnNOS over heNOS. Submicromolar potencies for 6 and 7 in a mouse RAW cell assay demonstrated the ability of these compounds to inhibit iNOS in a cellular environment. These latter compounds were also found to be orally bioavailable and efficacious due to their ability to inhibit the increase in plasma nitrite/nitrate levels in a rat LPS model.


Characterization of reentrant circuits in left atrial macroreentrant tachycardia: critical isthmus block can prevent atrial tachycardia recurrence.
Left atrial macroreentrant tachycardia (LAMRT) has not been characterized in detail. Twenty-eight patients with LAMRT, including 4 patients with ablated typical atrial flutter (AFL), underwent electroanatomic mapping of the left atrium (LA) between February 1999 and October 2001. LA maps were performed during LAMRT in 26 patients and during sinus rhythm in 2 patients. Electrically silent areas or continuous lines of double potentials were identified as acquired anatomic barriers in all patients. In 23 of 26 patients with LAMRT mapping, 42 reentry circuits with a protected isthmus were identified. The isthmus was 11.8+/-5.9 mm wide, with the maximal amplitude of 0.07 to 3.61 mV. Radiofrequency pulses terminated all LAMRTs in 23 patients and resulted in conduction block across the isthmus in 20 patients. In 2 patients with sinus mapping, all identified isthmuses were ablated. Additionally, AFL was induced and ablated in 6 patients. Atrial tachycardia recurred in 4 patients: 3 patients without validated block across the isthmus presented with recurrence of the same LAMRT, and 1 patient without ablated cavotricuspid isthmus presented with AFL. All tachycardias were abolished during a second procedure. Of 25 patients with identified isthmuses, 20 patients were without atrial arrhythmia and 5 had only atrial fibrillation during a median follow-up of 14 months. The reentry circuit with a protected isthmus can be identified in 89% patients with LAMRT by electroanatomic mapping. The isthmuses were amenable to radiofrequency applications in most patients. No atrial tachycardia recurred in any patients with isthmus block.


Psychological effects on patient's relatives regarding their presence during resuscitation.
Introduction: Presence of family and patients' relatives throughout resuscitation procedure is one of the most challenging concerns. Methods: In an interventional (quasi-experimental) study that was conducted during a 6 months period, the patients' relatives were randomly divided into two groups of intervention (the relatives who were eager to be present throughout the resuscitation procedure- under the family protection protocol, all of the procedure steps were explained to the relatives by an expert nurse who was not involved in the resuscitation procedure and control group (those who were not invited routinely to be present throughout the resuscitation procedure. However, if the control group were eager to be present, they were allowed to observe the procedure (these people were not supported by the protocol). After 90 days, subjects were contacted through telephone and filled standard questionnaires (Hospital Anxiety and Depression Scale [HADS]) and Impact of Event Scale (IES) were completed for all subjects. These questionnaires focus on anxiety, depression and post-traumatic stress disorder (PTSD). The obtained data were analyzed. Results: One hundred thirty three relatives were divided into two groups of control (59 subjects) and intervention (74 people). No significant difference was observed between two groups regarding demographic features. The evaluation after 90 days revealed depression, anxiety disorders and PTSD to be significantly more prevalent in control group than the intervention group (P < 0.0001 ). Conclusion: Emotional and psychological support and intervention on the patients' relatives are efficient and can prevent the emergence of psychological disorders.


Continuous Renal Replacement Therapy: Forty-year Anniversary.
In 1977 Peter Kramer performed the first CAVH (continuous arteriovenous hemofiltration) treatment in Gottingen, Germany. CAVH soon became a reliable alternative to hemo- or peritoneal dialysis in critically ill patients. The limitations of CAVH spurred new research and the discovery of new treatments such as CVVH and CVVHD (continuous veno-venous hemofiltration and continuous veno-venous hemodialysis). The alliance with industry led to development of new specialized equipment with improved accuracy and performance in delivering continuous renal replacement therapies (CRRTs). Machines and filters have progressively undergone a series of technological steps, reaching a high level of sophistication. The evolution of technology has continued, leading to the development and clinical application of new membranes, new techniques and new treatment modalities. With the progress of technology, the entire field of critical care nephrology moved forward, expanding the areas of application of extracorporeal therapies to cardiac, liver and pulmonary support. A great deal of research made extracorporeal therapies an interesting option for the treatment of sepsis and intoxication and the additional use of sorbents was explored. With the progress in understanding the pathophysiology of acute kidney injury (AKI), new guidelines were developed, driving indications, modalities of prescription, monitoring techniques and quality assurance programs. Information technology and precision medicine have recently contributed to further evolution of CRRT, with the possibility of collecting data in large databases and evaluating policies and practice patterns. This is likely to ultimately result in improved patient care. CRRTs are 40 years old today, but they are still young and full of potential for further evolution.


Minimalistic Ditopic Ligands: An α-S,N-Donor-Substituted Alkyne as Effective Intermetallic Conjugation Linker.
The capability of donor-substituted alkynes to link different metal ions in a side-on carbon donor-chelate coordination mode is extended from the donor centers S and P to the second period element N. The complex [Tp'W(CO)2 {η(2) -C2 (S)(NHBn)}] (Tp'=hydrido-tris(3,5-dimethylpyrazolyl)borate, Bn=benzyl) bearing a terminal sulfur atom and a secondary amine substituent is accessible by a metal-template synthesis. Subsequent deprotonation allowed the formation of remarkably stable heterobimetallic complexes with the [(η(5) -C5 H5 )Ru(PPh3 )] and the [Ir(ppy)2 ] moiety. Electrochemical and spectroscopic investigations (cyclic voltammetry, IR, UV/Vis, luminescence, EPR), as well as DFT calculations, and X-ray structure determinations of the W-Ru complex in two oxidation states reveal a strong metal-metal coupling but also a limited delocalization of excited states.


Assessing the putative roles of X-autosome and X-Y interactions in hybrid male sterility of the Drosophila bipectinata species complex.
Interspecific F1 hybrid males of the Drosophila bipectinata species complex are sterile, while females are fertile, following Haldane's rule. A backcross scheme involving a single recessive visible marker on the X chromosome has been used to assess the putative roles of X-autosome and X-Y interactions in hybrid male sterility in the D. bipectinata species complex. The results suggest that X-Y interactions are playing the major role in hybrid male sterility in the crosses D. bipectinata x D. parabipectinata and D. bipectinata x D. pseudoananassae, while X-autosome interactions are largely involved in hybrid male sterility in the crosses D. malerkotliana x D. bipectinata and D. malerkotliana x D. parabipectinata. However, by using this single marker it is not possible to rule out the involvement of autosome-autosome interactions in hybrid male sterility. These findings also lend further support to the phylogenetic relationships among 4 species of the D. bipectinata complex.


[Distribution and size of the cleavage nuclei in fragmented eggs ofAcheta domesticus L. (Orthopteroidea) during early differentiation].
In the egg ofAcheta domesticus L., peripheral streaming alters the originally equidistant distribution of early (plasmodial) blastoderm nuclei. Nuclei accumulate in the egg region between 10 and 50% of egg length measured from the posterior pole, while in other egg regions the distance between nuclei increases. The crowded nuclei will form the germ anlage proper. As a first step they reduce their volumes considerably. In the present study, whole mounts of eggs separated during cleavage into 2 fragments were scored for nuclei of reduced volume. The results were compared to the capability of similar egg fragments to form complete or partial germ bands.In eggs separated at 30% egg length, most nuclei in the posterior fragment will suffer size reduction and, if development is allowed to proceed, will form complete germ bands. In the anterior fragments, nuclei which normally will participate in head formation are carried backwards by peripheral streaming and accumulate near the rear end of the fragment. However, their volumes do not decrease, and no germ bands parts will be formed in such fragments during further development; instead, the blastoderm is converted exclusively into extraembryonic covers. These results show that the streaming and crowding of nuclei as such are not sufficient to induce size reduction and the switch towards germ band formation. It is concluded that for these changes to occur some additional influence is needed. This should in normal development be exerted by the posterior egg region which was separated from the anterior fragment in the experiment.