Expression kinetics and mapping of the thymidine kinase transcript and an immediate-early transcript from channel catfish virus.
Three transcripts from the terminal repeat of the channel catfish virus (CCV; also known as ictalurid herpesvirus 1) genome were mapped by S1 nuclease and primer extension analyses as well as by cDNA sequencing. These transcripts, TR3, TR5/6, and TR6, are encoded by open reading frame (ORF) 3, ORFs 5 and 6, and ORF 6, respectively, and correspond to those previously identified by sequence analysis (A. J. Davison, Virology 186:9-14, 1992). ORF 5 has previously been determined to encode thymidine kinase, but ORF 3 and ORF 6 encode proteins of unknown function. Although all three transcripts accumulate to high levels in cells infected in the presence of cycloheximide, kinetic analysis demonstrates that TR5/6 and TR6 are either early or late transcripts that leak through the cycloheximide block. In addition, two transcripts from the terminal repeat of the CCV genome that were mapped previously and were thought to be immediate-early in character, TR8a/9 and TR9, exhibit kinetics characteristic of early or late transcripts. TR3 is an immediate-early transcript that appears to have a very short half-life. In the 3' untranslated region of TR3, there are three copies of an AU-rich element which has previously been shown to be involved in destabilization of the oncogene c-fos and granulocyte/macrophage colony-stimulating factor mRNAs. mRNA destabilization may represent another mechanism by which herpesviruses regulate the rapid switch in expression from immediate-early genes to early genes during the transition to the early phase of infection.


Maternal micronutrient consumption periconceptionally and during pregnancy: a prospective cohort study.
To examine overall micronutrient intake periconceptionally and throughout pregnancy in a population-based cohort of Australian women. In a prospective cohort study, micronutrient dosages were extracted from self-reported maternal supplement use, recorded pre-conception, and for each trimester of pregnancy. A food frequency scale (DQESv2) captured usual maternal diet for gestational weeks 14-26. The influence of sociodemographic and lifestyle factors associated with supplement use was examined using logistic regression, and changes in micronutrient intakes prior to and throughout pregnancy were assessed using repeated-measures ANOVA analyses. Metropolitan hospital sites in Melbourne, Australia. Women with a viable singleton pregnancy were recruited at less than 19 weeks' gestation (n 2146). Compared with non-users, women using supplements during pregnancy were more likely to have planned their pregnancy, be >25 years old, primiparous, Caucasian, non-smokers, have a tertiary education and be consuming a folate-rich diet. Intakes of folate, Fe and Zn were significantly lower in the periconceptional period, compared with other periods (P<0·001). Intakes below Recommended Daily Intake levels were common both periconceptionally and throughout pregnancy, with 19-46 % of women not meeting the Recommended Daily Intake for folate, 68-82 % for Fe and 17-36 % for Zn. Conversely, 15-19 % of women consumed beyond the recommended Upper Limit for folate and 11-24 % for Fe. The study highlights the need for improved public health education on nutritional needs during pregnancy, especially among women with lower educational achievements and income.


Low Grade Ovarian Serous Carcinoma - A Clinical-Morphologic Study.
Low grade ovarian serous carcinomas (LGSC) are rare tumors, representing only a small part of all ovarian carcinomas. The study included six LGSC cases for which we followed the clinical-epidemiological and morphological parameters depending on the tumoral stages. The tumors corresponded to stage I in four cases, in one case to stage II and in another case to stage III. The majority of the analyzed histopathological parameters were present in all tumoral stages. The accuracy of the diagnostic and the correct staging of the LGSC affected patients is very important, because the grade and stage of the serous ovarian tumors impose the therapy and the prognosis.


Chitotriosidase is a biomarker for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) leads to rapidly progressive dementia and is caused by mutations in the gene CSF1R. Neurodegeneration is driven by dysfunction of microglia, the predominant cell type expressing CSF1R in the brain. We assessed chitotriosidase, an enzyme secreted by microglia, in serum and cerebrospinal fluid of patients with ALSP. Chitotriosidase activity was highly increased in cerebrospinal fluid of patients and correlated inversely with disease duration. Of interest, presymptomatic CSF1R mutation carriers did not show elevated chitotriosidase levels. This makes chitotriosidase a promising new biomarker of disease activity for this rare disease.


Quantitative biokinetics of titanium dioxide nanoparticles after intravenous injection in rats: Part 1.
Submicrometer TiO2 particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also drug delivery applications are envisaged. Beyond exposure of occupational groups, this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs are poorly understood and in many investigations excessive doses are applied. The present study investigates the biokinetics and clearance of a low single dose (typically 40-400 μg/kg BW) of 48V-radiolabeled, pure TiO2 anatase nanoparticles ([48V]TiO2NP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous (IV) injection into female Wistar rats. Biokinetics and clearance were followed from one-hour to 4-weeks. The use of radiolabeled nanoparticles allowed a quantitative [48V]TiO2NP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chemical background levels possibly caused by dietary or environmental titanium exposure. Highest [48V]TiO2NP accumulations were found in liver (95.5%ID after one day), followed by spleen (2.5%), carcass (1%), skeleton (0.7%) and blood (0.4%). Detectable nanoparticle levels were found in all other organs. The [48V]TiO2NP content in blood decreased rapidly after 24 h while the distribution in other organs and tissues remained rather constant until day-28. The present biokinetics study is part 1 of a series of studies comparing biokinetics after three classical routes of intake (IV injection (part 1), ingestion (part 2), intratracheal instillation (part 3)) under identical laboratory conditions, in order to test the common hypothesis that IV-injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes. This hypothesis is disproved by this series of studies.


Down-regulation of miR-10a-5p promotes proliferation and restricts apoptosis via targeting T-box transcription factor 5 in inflamed synoviocytes.
Synoviocytes from rheumatoid arthritis (RA) patients share certain features with tumor cells, such as over proliferation and invasion. Anomalous microRNA (miRNA) expression may participate in the pathogenesis of RA in different ways. The objective of the present study was to observe the role of miR-10a-5p targeting T-box transcription factor 5 (TBX5) gene on synoviocyte proliferation and apoptosis in RA. Human synovial sarcoma cell line, SW982 cells stimulating with interleukin-1β (IL-1β) were transfected with miR-10a-5p mimic and siRNA of TBX5. The real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis were used to evaluate the expression level of miR-10a-5p and TBX5 in SW982 cells respectively. Further, the proliferation and apoptosis of SW982 cells after treatment were determined by cell counting kit (CCK-8) and flow cytometry analysis respectively. We found that the miR-10a-5p showed down-regulated while TBX5 showed up-regulated expression in synoviocytes after stimulation with IL-1β. The miR-10a-5p mimic treatment showed a decline in cell proliferation while the increased rate of cell apoptosis as compared with control. Moreover, knockdown of TBX5 favored the apoptosis and reduced the cell proliferation as compared with control group. We conclude that down-regulation of miR-10a-5p promotes proliferation and restricts apoptosis via targeting TBX5 in inflamed synoviocytes.


Two cysteines in plant R2R3 MYB domains participate in REDOX-dependent DNA binding.
Plant R2R3 MYB domain proteins comprise one of the largest known families of transcription factors. Discrete evolutionary steps have shaped the plant-specific R2R3 MYB family from the broadly distributed R1R2R3 MYB proteins. R1R2R3 MYB domains have a single Cys residue (Cys-130) that needs to be reduced for DNA binding and transcriptional activity. In contrast, most R2R3 MYB domains contain two cysteines, Cys-49 and Cys-53, with Cys-53 at the equivalent position as Cys-130 in R1R2R3 MYB. Using the maize P1 regulator of flavonoid biosynthesis as a typical R2R3 MYB-domain protein, we investigated here the in vitro REDOX requirement for DNA binding by P1. We show that the C53S mutation requires reducing conditions for DNA-binding, whereas C53A binds DNA under oxidizing and reducing conditions. Neither mutation impairs the in vivo regulatory activity of P1. The C49S and C49A mutants bind DNA in vitro irrespective of the REDOX conditions. A C49I mutant, which simulates the MYB domain of c-MYB, binds DNA only under reducing conditions, and its binding is significantly affected by the C53S replacement. It is interesting that under non-reducing conditions, Cys-49 and Cys-53 form a disulfide bond that prevents the R2R3 MYB domain from binding DNA. Together, our results suggest that the evolutionary origin of Cys-49 within the plants has provided R2R3 MYB domains with a regulatory feature not present in animal MYB domains, highlighting fundamental structural and functional differences between similar DNA-binding domains from plants and animals.


Symptoms of pervasive developmental disorders as observed in prediagnostic home videos of infants and toddlers.
The objectives of this study were (1) to show prediagnostic abnormalities in social and communicative behaviors on home videos of children who later received a diagnosis of one of the pervasive developmental disorders (PDD) and (2) to demonstrate that prediagnostic abnormalities in social and communicative behaviors for children with PDD not otherwise specified will be less prominent than those in children with autistic disorder but still distinguishable from those of typically developing peers. Parents of children with PDD each submitted home videos of social events that were made when their child was between the ages of 12 and 30 months, before diagnosis. Two independent observers, unaware of the subjects' diagnoses or purpose of the study, scored the rates of specific anomalies in social and communicative behavior. Two additional observers scored the percentage of time the children were engaged socially or with objects. Data from the experimental group were compared with those of 25 age-matched children with no developmental disabilities. Significant differences were found between the rates of social engagement and 8 of the 25 specific behaviors of the children in whom PDD was later diagnosed and those of the typical children. The children later given the diagnosis of PDD not otherwise specified had mean frequencies of some social interactions and communicative skills that fell between those of children later given the diagnosis of autistic disorder and those of children with typical development. In our sample children in whom PDD was later diagnosed could be differentiated from their typically developing peers on the basis of specific anomalies noted in their social and communicative behaviors, especially joint attention. In our sample children with PDD not otherwise specified could have been further differentiated on the basis of the rates of social interaction. Careful assessment of social interaction and communicative behaviors may help to identify children with PDD before the age of 30 months.


Radiation Exposure of Interventional Radiologists during Computed Tomography Fluoroscopy-Guided Percutaneous Cryoablation.
The principal aim of this study was to evaluate radiation exposure of interventionalists during computed tomography (CT) fluoroscopy-guided percutaneous cryoablation (PCA) using radiophotoluminescent glass dosimeters (RPLDs). The radioprotective effects of safety glasses and lead apron were also evaluated. Radiation exposure of interventionalists during 46 CT fluoroscopy-guided PCA procedures was evaluated. Entrance surface dose (ESD) was measured using RPLDs on multiple sites: five sites, representing eye lens exposure; five sites, representing body exposure; and four sites, representing skin exposure. The ESD values on multiple sites were compared between different PCA procedures (renal, liver, and bone). The mean ESD on the X-ray-side hand exhibited the highest value (358.8 μGy). Regarding evaluation sites representing exposure to the eye lens, the highest ESD inside the radiation protective glasses was detected on the X-ray-side cheek (167.1 μGy). Most ESD values among multiple sites (10/14) were linearly correlated with CT fluoroscopy time. Among them, the ESD values measured during renal and liver PCA were relatively higher than those measured during bone PCA, especially on the chest area outside the lead apron, and on the X-ray tube-side elbow and hand during renal and bone PCA. Radioprotective effects of safety glasses and lead apron ranged from 44.6 to 50.6% and from 30.2 to 79.6%, respectively, on each evaluation site. The site with the highest radiation exposure on interventionalists during CT fluoroscopy-guided PCA was the X-ray tube-side hand. Radiation exposure of interventionalists was at acceptable levels and consistent with the recommended dose limits.


HomoplasyFinder: a simple tool to identify homoplasies on a phylogeny.
A homoplasy is a nucleotide identity resulting from a process other than inheritance from a common ancestor. Importantly, by distorting the ancestral relationships between nucleotide sequences, homoplasies can change the structure of the phylogeny. Homoplasies can emerge naturally, especially under high selection pressures and/or high mutation rates, or be created during the generation and processing of sequencing data. Identification of homoplasies is critical, both to understand their influence on the analyses of phylogenetic data and to allow an investigation into how they arose. Here we present HomoplasyFinder, a java application that can be used as a stand-a-lone tool or within the statistical programming environment R. Within R and Java, HomoplasyFinder is shown to be able to automatically, and quickly, identify any homoplasies present in simulated and real phylogenetic data. HomoplasyFinder can easily be incorporated into existing analysis pipelines, either within or outside of R, allowing the user to quickly identify homoplasies to inform downstream analyses and interpretation.


Antibacterial Effect of Chrysanthemum Buds' Crude Extract Against Salmonella Typhimurium and Potential Application in Cooked Chicken.
The objective of this study was to clarify the antibacterial activity and mechanism of Chrysanthemum buds' crude extract (CBCE) against Salmonella Typhimurium, and explore the potential application in cooked chicken. The zone of inhibition (ZI), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were used to assess the in vitro antibacterial activity of CBCE against Salmonella Typhimurium. The antibacterial mechanism was elucidated by revealing the changes in intracellular adenosine 5'-triphosphate (ATP) concentration, membrane potential, content of biomacromolecule, and cell morphology. Furthermore, the effect of CBCE on the counts of Salmonella Typhimurium and color of cooked chicken during storage was studied. The results showed that the ZI, MIC, and MBC of CBCE against Salmonella Typhimurium were 12.9 ± 0.53-13.6 ± 0.14 mm, 40, and 80 mg/mL, respectively. In the process of inhibiting Salmonella Typhimurium by CBCE, the reduction of intracellular ATP concentration, cell membrane depolarization, leakage of protein and nucleic acid, and destruction of cell morphology were observed. Moreover, after treatments with CBCE, the growth of Salmonella Typhimurium in cooked chicken was significantly inhibited (p < 0.05) compared with the control group. No significant differences (p > 0.05) in lightness (L*), redness (a*), and yellowness (b*) values of cooked chicken were found between untreated and treated samples, as well as the color of cooked chicken treated with CBCE did not change significantly (p > 0.05) during the six days of storage. Overall, our findings suggested that CBCE exhibited the antibacterial effect against Salmonella Typhimurium, and had the potential to be used as a natural food preservative for the control of Salmonella Typhimurium in chicken products.


Genetic profiling of hepatocellular carcinoma using next-generation sequencing.
Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, both clinically and from a molecular standpoint. The advent of next-generation sequencing technologies has provided new opportunities to extensively analyze molecular defects in HCC samples. This has uncovered major cancer driver genes and associated oncogenic pathways operating in HCC. More sophisticated analyses of sequencing data have linked specific nucleotide patterns to external toxic agents and defined so-called 'mutational signatures' in HCC. Molecular signatures, taking into account intra- and inter-tumor heterogeneity, and their functional validation could provide useful data to predict treatment response to molecular therapies. In this review we will focus on the current knowledge of deep sequencing in HCC and its foreseeable clinical impact.


Measuring the electron temperature and identifying plasma detachment using machine learning and spectroscopy.
A machine learning approach has been implemented to measure the electron temperature directly from the emission spectra of a tokamak plasma. This approach utilized a neural network (NN) trained on a dataset of 1865 time slices from operation of the DIII-D tokamak using extreme ultraviolet/vacuum ultraviolet emission spectroscopy matched with high-accuracy divertor Thomson scattering measurements of the electron temperature, Te. This NN is shown to be particularly good at predicting Te at low temperatures (Te < 10 eV) where the NN demonstrated a mean average error of less than 1 eV. Trained to detect plasma detachment in the tokamak divertor, a NN classifier was able to correctly identify detached states (Te < 5 eV) with a 99% accuracy (an F1 score of 0.96) at an acquisition rate 10× faster than the Thomson scattering measurement. The performance of the model is understood by examining a set of 4800 theoretical spectra generated using collisional radiative modeling that was also used to predict the performance of a low-cost spectrometer viewing nitrogen emission in the visible wavelengths. These results provide a proof-of-principle that low-cost spectrometers leveraged with machine learning can be used to boost the performance of more expensive diagnostics on fusion devices and be used independently as a fast and accurate Te measurement and detachment classifier.


Paraparesis caused by an angiolipomatous hamartoma in an adolescent with Proteus syndrome and scoliosis.
This 16-year-old boy with Proteus syndrome suffered acute spinal cord compression secondary to hemorrhage into an extradural paraspinal angiolipomatous hamartoma. A magnetic resonance (MR) imaging study performed 12 years earlier had revealed the presence of this tumor at the apex of a mild thoracic scoliosis, which had been stable during the intervening decade. Spinal cord neurological deficit in Proteus syndrome is rare. It can arise either from vertebral abnormalities and kyphoscoliotic deformities or from tumor encroachment. The authors describe the temporal evolution of scoliosis and acute spinal cord compression caused by a paraspinal angiolipomatous hamartoma over a period of 12 years. A review of the literature suggests that regular follow up, including serial MR imaging, is indicated in children with Proteus syndrome and scoliosis. Earlier resection of extradural tumor mass encroaching on the cord is warranted in the treatment of these children.


FOXM1 nuclear transcription factor translocates into mitochondria and inhibits oxidative phosphorylation.
Forkhead box M1 (FOXM1), a nuclear transcription factor that activates cell cycle regulatory genes, is highly expressed in a majority of human cancers. The function of FOXM1 independent of nuclear transcription is unknown. In the present study, we found the FOXM1 protein inside the mitochondria. Using site-directed mutagenesis, we generated FOXM1 mutant proteins that localized to distinct cellular compartments, uncoupling the nuclear and mitochondrial functions of FOXM1. Directing FOXM1 into the mitochondria decreased mitochondrial mass, membrane potential, respiration, and electron transport chain (ETC) activity. In mitochondria, the FOXM1 directly bound to and increased the pentatricopeptide repeat domain 1 (PTCD1) protein, a mitochondrial leucine-specific tRNA binding protein that inhibits leucine-rich ETC complexes. Mitochondrial FOXM1 did not change cellular proliferation. Thus, FOXM1 translocates into mitochondria and inhibits mitochondrial respiration by increasing PTCD1. We identify a new paradigm that FOXM1 regulates mitochondrial homeostasis in a process independent of nuclear transcription.


The role of cellular susceptibility in the declining severity of respiratory influenza of ferrets with age.
A comparison was made, both in vivo and in organ culture, between newborn (1-day-old) and suckling (15-day-old) ferrets of lower respiratory tract tissue infected with a virulent strain (clone 7a) of influenza virus. Newborn ferrets were killed by influenza virus following intranasal inoculation but suckling ferrets were almost as resistant as adult ferrets. In newborn ferrets there was a rapid, severe and progressive infection of lung tissue with infection of alveolar cells as well as those of bronchial and bronchiolar epithelium (assessed by monitoring virus infectivity and by fluorescent antibody staining). In suckling ferrets, as previously shown for adult animals, the lung infection was less severe, less persistent and confined to the epithelium of bronchi with only a small bronchiolar involvement and even less alveolar cell infection. These differences observed in vivo were repeated in organ cultures obtained from various areas of the lung. i.e. alveolar and airway epithelial cells of newborn ferrets exhibited a greater susceptibility than those of older ferrets. Thus, it appears that one factor determining the greater susceptibility of the lower respiratory tract of newborn ferrets is a greater inherent susceptibility of alveolar and airway epithelial cells to infection with influenza virus. Other factors may also be involved and have yet to be investigated.


Electrophysiological evaluation of genito-sphincteric dysfunction in multiple system atrophy.
Thirteen patients with multiple system atrophy underwent multimodality neurophysiological evaluation, including sphincteric needle electromyography (EMG), sacral reflexes, pudendal nerve terminal latency, pudendal (PSEPs) and tibialis posterior nerve somatosensory evoked potentials (TPSEPs), and perineal motor evoked potentials (PMEPs). EMG revealed denervation or neurogenic changes, with reduction in spontaneous tonic activity at rest and abnormal pudendal nerve terminal latency in 10 patients (76.9%); anal reflex was delayed in 7 patients (53.8%). TPSEPs scalp responses were clearly abnormal in 4 patients (30.7%), whereas PSEPs exhibited changes in 9 (69.2%): in 6 patients responses were delayed at lumbar level (46.2%), and in 5 over the scalp (38.4%). PMEPs showed an increase in latency with a mild prolongation of central motor conduction time (CMCT) in 2 cases (15.3%); 1 patient had prolonged latencies following both cortical and sacral stimulation, but a normal CMCT. Even if diagnostic yield is not improved using these investigations they provide evidence of multiple lesion sites other than Onuf's nucleus.


Solid residues from Italian municipal solid waste incinerators: A source for "critical" raw materials.
The incineration of municipal solid wastes is an important part of the waste management system along with recycling and waste disposal, and the solid residues produced after the thermal process have received attention for environmental concerns and the recovery of valuable metals. This study focuses on the Critical Raw Materials (CRM) content in solid residues from two Italian municipal waste incinerator (MSWI) plants. We sampled untreated bottom ash and fly ash residues, i.e. the two main outputs of common grate-furnace incinerators, and determined their total elemental composition with sensitive analytical techniques such as XRF and ICP-MS. After the removal of a few coarse metallic objects from bottom ashes, the corresponding ICP solutions were obtained using strong digestion methods, to ensure the dissolution of the most refractory components that could host significant amounts of precious metals and CRM. The integration of accurate chemical data with a substance flow analysis, which takes into account the mass balance and uncertainties assessment, indicates that bottom and fly ashes can be considered as a low concentration stream of precious and high-tech metals. The magnesium, copper, antimony and zinc contents are close to the corresponding values of a low-grade ore. The distribution of the elements flow between bottom and fly ash, and within different grain size fractions of bottom ash, is appraised. Most elements are enriched in the bottom ash flow, especially in the fine grained fractions. However, the calculated transfer coefficients indicate that Sb and Zn strongly partition into the fly ashes. The comparison with available studies indicates that the CRM concentrations in the untreated solid residues are comparable with those residues that undergo post-treatment beneficiations, e.g. separation between ferrous and non-ferrous fractions. The suggested separate collection of "fresh" bottom ash, which could be processed for further mineral upgrading, can constitute an attractive option of the waste management system, when physical-mechanical devices are not available or could not be implemented in old MSWI systems. The suggested procedure may lead to the improvement of recovery efficiency up to 83% for CRM and 94% for other valuable metals.


Assessment of diabetic autonomic neuropathy using twenty-four-hour spectral analysis of heart rate variability: a comparison with the findings of the Ewing battery.
A power spectral analysis of heart rate variability has been applied in order to assess diabetic autonomic neuropathy and high frequency spectra are thus considered to possibly reflect vagal nerve integrity in patients with diabetes mellitus. The purpose of this study was to investigate the relationship between the findings of high frequency spectra analysis and the results of the Ewing battery. We performed 24-hour power spectral analysis using an ambulatory ECG monitoring system and standard tests in order to assess diabetic autonomic neuropathy (Ewing battery) in 18 diabetic patients to compare their diagnostic values for diabetic autonomic neuropathy. We used the high frequency amplitude (high frequency spectra; 0.15-0.40 Hz) as a direct measure of vagal nerve integrity from each hourly spectral plot. All hourly high frequency spectra decreased along with the impaired assessment of the battery, especially during the night when the high frequency spectra showed a manifest increase in patients classified as normal according to the battery. High frequency spectra during the night while asleep (22:00-05:00) and during a 24-hour period significantly correlated with the results of the battery. These values markedly decreased even in patients classified as having early vagal damage when compared with those classified as normal. High frequency spectra during night closely reflected the intrinsic vagal nerve integrity in patients with diabetes mellitus. High frequency spectra during night or a 24-hour period is a simple and sensitive measure of diabetic autonomic neuropathy and is considered to be a useful modality for detecting even early changes in autonomic dysfunction.


Evaluation of clinical effectiveness of MIST ultrasound therapy for the healing of chronic wounds.
(1) To determine the incidence of wound closure for chronic nonhealing lower extremity wounds of various etiologies using MIST ultrasound therapy, a 510(K)-approved, low-frequency, noncontact ultrasound device indicated for the cleansing and debridement of chronic wounds. (2) To determine the optimum treatment duration for therapy with this low-frequency, noncontact ultrasound device, quantifying end points that correlate with a maximal clinical response and identifying potential synergistic therapies that could be used in conjunction with this therapy. (3) To analyze the impact of low-frequency noncontact ultrasound therapy on the microcirculatory flow patterns within the wound bed. A noncomparative clinical outcomes trial utilizing low-frequency, noncontact ultrasound. A tertiary-referral hospital-based wound clinic. Twenty-three patients from a single tertiary-referral hospital-based wound clinic. Control data were obtained from a previously published, prospectively collected database from the same clinic. During an 8-month period, a total of 29 lower extremity wounds in 23 patients who met criteria for inclusion were treated with low-frequency, noncontact ultrasound therapy. Standard of care was provided for 2 weeks for all wounds screened for the study. A failure to achieve an area reduction greater than 15% qualified the patient for enrollment to the trial and the addition of low-frequency, noncontact ultrasound therapy to the current treatment regimen. Wound healing, area and volume reduction, and laser Doppler-derived mean voltage (a marker for microcirculatory flow) are the main outcome measures for the study. Overall, 69% of the wounds in the study were healed using an intent-to-treat model. When low-frequency, noncontact ultrasound was used as a stand-alone device, median time to healing was 7 weeks. Historic controls were healed with a median time to healing of 10 weeks; however, a statistically significant number of these patients required wound-related hospitalization and surgical procedures to achieve closure compared with the wounds in the present study. Treatment with low-frequency, noncontact ultrasound achieved healing in chronic wounds when used as a stand-alone device or in combination with moist wound care in 69% of cases. Response to low-frequency, noncontact ultrasound was evident within 4 weeks of therapy. Earlier transition to secondary procedures and decreased utilization of inpatient care might result in more cost-effective wound healing than the current standard of care. A well-designed health economic-based trial is warranted to assess this technology.


DNA topoisomerase II sites in the histone H4 gene during the highly synchronous cell cycle of Physarum polycephalum.
The nearly perfect synchrony of nuclear division in a plasmodium of Physarum polycephalum provides a powerful system to analyze topoisomerase II cleavage sites in the course of the cell cycle. The histone H4 locus, whose schedule of replication and transcription is precisely known, was chosen for this analysis. Drug-induced topoisomerase II sites are clustered downstream of the histone H4 gene and appear highly dependent on cell cycle stage. They were only detected in mitosis and at the very beginning of S phase, precisely at the time of replication of the histone H4 region. The sites, which were absent in G2 phase, reappeared at the next mitosis. Remarkably, DNase I hypersensitive sites occurred in nearly the same location, but their schedule was totally different: they were absent in mitosis and present in G2. This schedule follows H4 transcription, which peaks in mid-S phase and in the second part of G2 phase and is off during mitosis. These results suggest that topoisomerase II may not be involved in transcription, but plays a role in remodeling chromatin structure, both during chromosome condensation in prophase/metaphase to allow their decatenation and during chromosome decondensation after metaphase to allow replication fork passage throughout the region.


A rare case of medullary carcinoma of the colon presenting as intussusception in an adult with rectal bleeding.
Medullary carcinoma is a recently recognized rare subtype of colorectal cancer resembling both poorly differentiated adenocarcinoma and neuroendocrine tumors. Medullary carcinoma most commonly presents in the proximal colon and can be differentiated from other right-sided malignant lesions by histology and immunochemical markers. We present here a rare case of an adult patient with rectal bleeding who was found to have an intussusception due to underlying medullary carcinoma of the splenic flexure. A 72-year-old woman presented to our GI clinic with rectal bleeding. Colonoscopy revealed a necrotic mass of the sigmoid colon, later determined by CT to be a colo-colonic intussusception at the level of the splenic flexure. Patient underwent diagnostic laparoscopy with findings of a large splenic flexure mass, which was resected and found to be medullary carcinoma of the colon. The tumor was poorly differentiated and exhibited microsatellite instability but was discovered at an early stage and thus did not require any adjuvant chemotherapy. Unlike most previously reported cases of medullary carcinoma, our patient presented with a left sided tumor. To our knowledge, this is the first report of a medullary colon cancer presenting with intussusception.


Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I.
Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by the occurrence of nerve sheath tumors and considerable clinical heterogeneity. Some translational studies have been limited by the lack of animal models available for assessing patient-specific mutations. In order to test therapeutic approaches that might restore function to the mutated gene or gene product, we developed mice harboring NF1 patient-specific mutations including a nonsense mutation (c.2041C>T; p.Arg681*) and a missense mutation (c.2542G>C; p.Gly848Arg). The latter is associated with the development of multiple plexiform neurofibromas along spinal nerve roots. We demonstrate that the human nonsense NF1(Arg681*) and missense NF1(Gly848Arg) mutations have different effects on neurofibromin expression in the mouse and each recapitulates unique aspects of the NF1 phenotype, depending upon the genetic context when assessed in the homozygous state or when paired with a conditional knockout allele. Whereas the missense Nf1(Gly848Arg) mutation fails to produce an overt phenotype in the mouse, animals homozygous for the nonsense Nf1(Arg681*) mutation are not viable. Mice with one Nf1(Arg681*) allele in combination with a conditional floxed Nf1 allele and the DhhCre transgene (Nf1(4F/Arg681*); DhhCre) display disorganized nonmyelinating axons and neurofibromas along the spinal column, which leads to compression of the spinal cord and paralysis. This model will be valuable for preclinical testing of novel nonsense suppression therapies using drugs to target in-frame point mutations that create premature termination codons in individuals with NF1.


Phototoxicity in an ultraviolet ink manufacturing plant.
Ultraviolet (UV) dyes are used as inks in garment printing. Hypersensitivity reactions to these compounds have been reported in the literature. The authors report a case of reaction to UV ink in a patient already on corticosteroid therapy. The patient's clinical course was reviewed along with images of wounds that subsequently developed. The affected areas were debrided and covered with Vaseline gauze and silver impregnated dressings. Epithelium was salvaged in many areas, and regrowth occurred over several weeks in regions of deeper injury. The concurrent use of steroids and the rapidity of the onset of symptoms were not characteristic of hypersensitivity dermatitis, which has previously been reported. The cause of the wounds was likely phototoxicity from radical subtypes in the ink that catalyze the reaction when exposed to UV light.


A generalized strategy for immobilizing uniformly oriented membrane proteins at solid interfaces.
We have developed a method based on self-assembly of thiols on Au substrates to immobilize membrane proteins at interfaces. Using water soluble nitrilotriacetic acid (NTA)-terminated oligo(ethylene glycol) thiols, a histidine-tagged G protein-coupled membrane receptor (GPCR) was captured in a defined orientation with little nonspecific binding.


Role of common gamma chain utilizing cytokines for immune reconstitution in HIV infection.
Many cytokines that utilize the common gamma (Cgamma) chain signaling pathway, viz Interleukin (IL)-2, IL-15, and IL-7 are known to be important for inducing T cell maturation, proliferation, or survival. Untreated chronic HIV infection is associated with profound quantitative and qualitative deficiency of CD4 T cells, which is partially reversed following highly active antiretroviral therapy (HAART). A subset of patients, however, fail to recover CD4 T cells despite virologic suppression. The role of Cgamma chain cytokines in influencing immune reconstitution following potent antiretroviral therapy is discussed. Maturation markers (naïve, central memory, effector memory, and effector), cytokine receptors IL-2Rbeta, Cgamma chain, IL-7Ralpha, IL-15Ralpha, and cytokine-induced proliferative responses of T cells in a cohort of HIV-infected pediatric patients and adults classified on the basis of immunologic and virologic response to antiretroviral therapy were examined. The studies indicated that patients had increased percentages of effector memory CD8+ T cells in comparison to healthy volunteers. While patients with partially controlled viremia and poor CD4 T cell reconstitution manifested poor proliferative responses to anti-CD3 or HIV gag antigen stimulation, proliferative responses to Cgamma chain utilizing cytokines IL-2, IL-7, and IL-15 were robust. Another Cgamma chain utilizing cytokine, IL-21 had no influence on cellular proliferation but enhanced perforin expression in effector CD8 T cells. Thus, cytokine receptor deficiencies may contribute to immune deficiency in HIV-infected patients, and Cgamma chain cytokines may play an important role in vivo in immune homeostasis in lymphopenic patients by maintaining the memory subsets of T cells in patients with CD4 T cell deficiency.


Design Principles for Using Amphiphilic Polymers To Create Microporous Water.
Aqueous dispersions of microporous nanocrystals with dry, gas-accessible pores─referred to as "microporous water"─enable high densities of gas molecules to be transported through water. For many applications of microporous water, generalizable strategies are required to functionalize the external surface of microporous particles to control their dispersibility, stability, and interactions with other solution-phase components─including catalysts, proteins, and cells─while retaining as much of their internal pore volume as possible. Here, we establish design principles for the noncovalent surface functionalization of hydrophobic metal-organic frameworks with amphiphilic polymers that render the particles dispersible in water and enhance their hydrolytic stability. Specifically, we show that block co-polymers with persistence lengths that exceed the micropore aperture size of zeolitic imidazolate frameworks (ZIFs) can dramatically enhance ZIF particle dispersibility and stability while preserving porosity and >80% of the theoretical O2 carrying capacity. Moreover, enhancements in hydrolytic stability are greatest when the polymer can form strong bonds to exposed metal sites on the external particle surface. More broadly, our insights provide guidelines for controlling the interface between polymers and metal-organic framework particles in aqueous environments to augment the properties of microporous water.


Pseudoxanthoma Elasticum-Like Papillary Dermal Elastolysis: A Single Case Report.
Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-PDE), a rare acquired elastolytic disorder, occurs in postmenopausal, elderly women and is characterized by soft, white-yellow papules that localize on the neck and supraclavicular regions and often coalesce into cobblestone plaques. It has no systemic involvement and is histologically distinct from the clinically similar inherited pseudoxanthoma elasticum. A 64-year-old Caucasian woman presented with a 2-year history of multiple, asymptomatic soft yellow 1- to 2-mm papules on her neck, which were increasing in number. On histopathology, haemotoxylin and eosin stain showed a normal-appearing papillary dermis; however, Verhoeff-van Gieson elastic stain showed absent elastic fibres in the papillary dermis. Papular elastorrhexis was suggested, but given its clinical picture, PXE-PDE was also considered. There was no resolution after 2 courses of intralesional triamcinolone acetonide (0.1 mL of 5 mg/mL). PXE-PDE, which is characterized by complete loss or significant reduction of elastic fibres in the papillary dermis, was consistent with our patient's presentation and histologic findings. Papular elastorrhexis, a paediatric cutaneous disorder, was initially considered, but clinicopathologic correlation led to a diagnosis of PXE-PDE. Intralesional corticosteroids was tried as a treatment but was ineffective at improving the condition. This report documents the importance of histopathology and clinicopathologic correlation when differentiating the overlapping variants of fibroelastolytic disease.


[Xin'an Dispensaries and its role in medicine in the Ming-Qing dynasties].
The Xin'an Dispensaries were set up in the Song dynasty, completed in the Ming dynasty and reached its peak of development at the end of the Qing dynasty. The representative ones of the dispensaries include Lu's Baohetang of the Song dynasty, Xu's Baoyuantang, Zhengtian dispensary, and Baoyutang of the Ming dynasty, Hu Xian Chun, Zhongdetang of the Qing dynasty. All these dispensaries were mostly run by the physicians themselves in the Ming dynasty, while they were run by Anhui businessmen in the Qing dynasty. As a union embodying health care, production and trading of traditional handicraft, not a few of them had become famous pharmaceutical factories today, such as Hu Qing Yu Tang, Jianmin Pharmaceutical Factory of Wuhan. Rich experience on production and management were accumulated, alongside achievements on prescription, drug processing, storage, collection and ready-made drug manufacturing.


The brain and computer: The neurosurgical interface.
Neurosurgery has always had a strong interest in innovating new technologies to improve neurological function and quality of life. Now, novel interventions that modulate central nervous system activity at the nanoparticle, molecular, genetic, cellular, and network level all seem to be on the horizon. Advances in biomedical engineering, including imaging techniques, sensor technologies, bio-signal analyses and classification, and prosthetics, have particularly accelerated the development brain-computer interfaces (BCI). Clinical translation of BCI technology will require multidisciplinary collaboration and effort to develop all necessary components, including advanced sensor technologies, sophisticated and real-time signal analyses and classifications, and complex effector technologies. Although the field has primarily been driven by basic scientists, neurosurgeons need to play a critical role in the further development of each component of these technologies because of our unique access to the awake and behaving human brain, our perspective with respect to the practicalities of technology implementation in the clinical setting, and because of our historical commitment to improving neurological function and quality-of-life. The current state of BCI research, the challenges, and the critical role that neurosurgeons must play in BCI development are briefly reviewed to advocate for increased neurosurgical involvement and commitment to this emerging translational field.


'A man can be destroyed but not defeated': Ernest Hemingway's near-death experience and declining health.
Ernest Hemingway is one of the most popular and widely acclaimed American writers of the 20th century. His works and life epitomize the image of the hyper-masculine hero, facing the cruelties of life with 'grace under pressure'. Most of his writings have a quasi-autobiographical quality, which allowed many commentators to draw comparisons between his personality and his art. Here, we examine the psychological and physical burdens that hindered Hemingway's life and contributed to his suicide. We first take a look at his early years, and review his psychopathology as an adult. A number of authors have postulated specific diagnoses to explain Hemingway's behavior: borderline personality disorder, bipolar disorder, major depression, multiple head trauma, and alcoholism. The presence of hemochromatosis, an inherited metabolic disorder, has also been suggested. We describe the circumstances of his suicide at 61 as the outcome of accumulated physical deterioration, emotional distress and cognitive decline. Special attention is paid to the war wound he suffered in 1918, which seemed to involve a peculiar altered state of consciousness sometimes called 'near-death experience'. The out-of-body experience, paradoxical analgesia and conviction that dying is 'the easiest thing' seemed to infl uence his future work. The constant presence of danger, death, and violence in his works, as well as the emphasis on the typical Hemingway 'code hero', can all be traced to particular psychological and neurological disorders, as well as his early brush with death.


Central Metabolism in Mammals and Plants as a Hub for Controlling Cell Fate.
Significance: The importance of oxidoreductases in energy metabolism together with the occurrence of enzymes of central metabolism in the nucleus gave rise to the active research field aiming to understand moonlighting enzymes that undergo post-translational modifications (PTMs) before carrying out new tasks. Recent Advances: Cytosolic enzymes were shown to induce gene transcription after PTM and concomitant translocation to the nucleus. Changed properties of the oxidized forms of cytosolic glyceraldehyde 3-phosphate dehydrogenase, and also malate dehydrogenases and others, are the basis for a hypothesis suggesting moonlighting functions that directly link energy metabolism to adaptive responses required for maintenance of redox-homeostasis in all eukaryotes. Critical Issues: Small molecules, such as metabolic intermediates, coenzymes, or reduced glutathione, were shown to fine-tune the redox switches, interlinking redox state, metabolism, and induction of new functions via nuclear gene expression. The cytosol with its metabolic enzymes connecting energy fluxes between the various cell compartments can be seen as a hub for redox signaling, integrating the different signals for graded and directed responses in stressful situations. Future Directions: Enzymes of central metabolism were shown to interact with p53 or the assumed plant homologue suppressor of gamma response 1 (SOG1), an NAM, ATAF, and CUC transcription factor involved in the stress response upon ultraviolet exposure. Metabolic enzymes serve as sensors for imbalances, their inhibition leading to changed energy metabolism, and the adoption of transcriptional coactivator activities. Depending on the intensity of the impact, rerouting of energy metabolism, proliferation, DNA repair, cell cycle arrest, immune responses, or cell death will be induced. Antioxid. Redox Signal. 34, 1025-1047.


Comparison of antibacterial effects of a carrier produced in microemulsion system from aqueous extract of Aloe vera with selected antibiotics on Enterobacteriacea.
Antibiotics resistance has recently increased. The aim of this study was the evaluation of antibacterial efficacy of Aloe vera carrier produced in microemulsion system in comparison with ordinary antibiotics against some Enterobacteriacea. The aquatic extract of Aleo vera was produced by the Soxhlet method and a nonocarrier in the microemulsion system was prepared by two emulsifiers. The clinical isolates of Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Shigella dysenteriae, Salmonella Typhimurium, Salmonella Paratyphi, Serratia marcescens, Proteus mirabilis, Enterobacter aerogenes, Citrobacter freundii and Morganella morganii were obtained from patients and were identified by microbiological methods. Diffusion disk was used for evaluation of antibacterial properties in comparison with selected ordinary antibiotics. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) for tested materials were determined using MTT in the Micro Broth dilution method. The results proved that effect of carrier on studied isolates is dependent on concentration level. The inhibitory effect of carrier in concentration of 15 μg/ml by 18 mm zone of inhibition for Klebsiella pneumoniae was comparable to Ceftazidime and Cefalothin. The lowest MIC and MBC determined by the Microbroth dilution method with MTT belonged to Klebsiella pneumoniae as 0.1 and 3 μg/ml and higher concentrations belonged to Enterobacter aerogenes at 7 and 15 μg/ml. The greatest effect of carrier of Aleo vera aquatic extract was observed for Klebsiella pneumoniae and the lowest effect belonged to Enterobacter aerogenes, Citrobacter freundii and Morganella morganii. It was concluded that the carrier of Aloe vera produced in microemulsion system was most effective and had equal effects in comparison with ordinary antibiotics against Enterobacteriacea.


Lysosome calcium in ROS regulation of autophagy.
Lysosomes, the cell's recycling center, undergo nutrient-sensitive adaptive changes in function and biogenesis, i.e., lysosomal adaptation. We recently discovered that lysosomes also mediate the cell's "survival" response (i.e., autophagy) to oxidative stress through the activation of TFEB (transcription factor EB), a master regulator of lysosome biogenesis and autophagy. MCOLN1/TRPML1, the principal Ca2+ release channel on the lysosomal membrane, serves as the redox sensor in this process. Increasing reactive oxygen species (ROS) levels, either endogenously by mitochondrial damage or exogenously, directly activates MCOLN1 to induce lysosomal Ca2+ release, triggering PPP3/calcineurin-dependent TFEB nuclear translocation to enhance autophagy. Hence, ROS may induce autophagy by activating the MCOLN1-lysosome Ca2+-TFEB pathway, facilitating the removal of damaged mitochondria and excess ROS. Our findings have revealed a lysosomal signaling mechanism for cells to respond to oxidative bursts and adapt to oxidative stress.


Nearly monodispersed MoS2 hierarchical architectures as superior anodes for electrochemical lithium-storage.
In this paper, we developed a facile approach to synthesize well-dispersed 3D hierarchical porous MoS2 architectures with assistance of polyacrylate and demonstrated their applications in lithium ion batteries (LIBs). It was confirmed that the uniform flower-like MoS2 architectures were assembled by nanosheets comprising about ∼10 stacking layers. Polyacrylate was revealed to have a significant impact on controlling the formation of the uniform hierarchical flower-like architectures with desirable dispersity. It was believed that the polyacrylate could direct assembly of the MoS2 nanosheets into hierarchical structures and could well stabilize and disperse MoS2 architectures. Furthermore, a stable cycling capability (839 mAh g-1 at 0.1 A g-1 after 120 cycles) and superior rate ability of the MoS2 architectures were achieved as anodes for LIBs. This remarkably enhanced electrochemical property could be ascribed to their beneficial structural features and surface-dominated capacitive contribution.


β-Cell Ca(2+) dynamics and function are compromised in aging.
Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of β-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse β-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased β-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype.


Radiation protection by Ex-RAD: a systematic review.
Protection of normal tissues against ionizing radiation-induced damages is a critical issue in clinical and environmental radiobiology. One of the ways of accomplishing radiation protection is through the use of radioprotectors. In the search for the most effective radioprotective agent, factors such as toxicity, effect on tumors, number of tissues protected, ease of administration, long-term stability, and compatibility with other drugs need to be assessed. Thus, in the present study, we systematically review existing studies on a chemical radioprotector, Ex-RAD, with the aim of examining its efficacy of radiation protection as well as underlying mechanisms. To this end, a systematic search of the electronic databases including Pubmed, Scopus, Embase, and Google Scholar was conducted to retrieve articles investigating the radioprotective effect of Ex-RAD. From an initial search of 268 articles, and after removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 10 articles were finally included for this systematic review. Findings from the reviewed studies indicated that Ex-RAD showed potentials for effective radioprotection of the studied organs with no side effect. Furthermore, the inhibition of apoptosis through p53 signaling pathway was the main mechanism of radioprotection by Ex-RAD. However, its radioprotective effect would need to be investigated for more organs in future studies.


Synthesis of CuPF6 -(S)-BINAP loaded resin and its enantioselectivity toward phenylalanine enantiomers.
A type of resin-anchored CuPF6 -(S)-BINAP was synthesized and identified. The PS-CuPF6 -(S)-BINAP resin was used to adsorb the phenylalanine enantiomers. The results showed that the adsorption capacity of PS-CuPF6 -(S)-BINAP resin toward L-phenylalanine was higher than that of resin toward D-phenylalanine. PS-CuPF6 -(S)-BINAP resin exhibited good enantioselectivity toward L-phenylalanine and D-phenylalanine. The influence of phenylalanine concentration, pH, adsorption time, and temperature on the enantioselectivity of the resin were investigated. The results showed that the enantioselectivity of the resin increased with increasing the phenylalanine concentration, pH, and adsorption time, while it decreased with an increase in temperature. The causes for these influences are discussed. The highest enantioselectivity (α = 2.81) was obtained when the condition of phenylalanine concentration was 0.05 mmol/mL, pH was 8, adsorption time was 12 h, and temperature 5°C. The desorption test for removing D/L-phenylalanine on PS-CuPF6 -(S)-BINAP resin was also investigated. The desorption ratios of D-phenylalanine and L-phenylalanine at pH of 1 were 95.7% and 94.3%, respectively. This result indicated that the PS-CuPF6 -(S)-BINAP resin could be regenerated by shaking with an acidic solution. The reusability of the PS-CuPF6 -(S)-BINAP resin was also assessed and the resin exhibited considerable reusability.


Association between Minimal Change Esophagitis and Gastric Dysmotility: A Single-Center Electrogastrography and Endoscopy Study in Children.
Minimal change esophagitis (MCE) is a reflux disease without mucosal breaks, known to be partially associated with abnormal gastric motor function. Electrogastrography (EGG) is commonly applied to assess gastric motor function in a noninvasive fashion. We aimed to determine the relationship between MCE and gastric myoelectrical activity (GME) recorded on EGG in children. We retrospectively assessed the records of 157 children without underlying disease who underwent both EGG and upper gastrointestinal endoscopy at Gachon University Gil Medical Center between January 2010 and June 2015. The children were stratified according to the appearance of the esophagus (normal vs. MCE). Between-group differences in EGG parameters and their correlation with each MCE finding were statistically analyzed. Only the power ratio, one of the EGG parameters analyzed, differed significantly between the two groups (MCE, 1.68±3.37 vs. normal, 0.76±1.06; p<0.05), whereas the other parameters, such as dominant frequency, dominant power, and the ratio of abnormal rhythm, showed no differences. Among children with MCE, significant correlations were noted between erythema and power ratio (p<0.05), friability and postprandial dominant frequency (p<0.05), and edema and/or accentuation of mucosal folds and pre-prandial frequency (p<0.05). Helicobacter pylori infection correlated with postprandial arrhythmia (MCE, 33.59±15.52 vs. normal, 28.10±17.23; p<0.05). EGG parameters did not differ between children with normal esophagus and those with biopsy-proven chronic esophagitis. In children with MCE, gastric dysmotility may affect the development of MCE, manifesting as EGG abnormalities. H. pylori infection may also affect GME. However, larger prospective investigations are needed to confirm these findings.


Microsporum canis infection in calves.
Microsporum canis infection, seldom reported in calves, is described. The organism was isolated from skin scrapings collected from ringworm lesions mainly on the heads of 2 naturally infected calves. The organism was studied in vitro, and experimentally on guinea-pigs.


Carbon source utilization and accumulation of respiration-related substances by freshwater Thioploca species.
Carbon source utilization of Thioploca species from freshwater and brackish lakes in Japan was investigated. Microautoradiography demonstrated that freshwater and brackish Thioploca samples assimilate acetate. In addition, vertical nitrate transportation by freshwater Thioploca was examined by measuring substances accumulated in Thioploca filaments. The filaments of Thioploca sp. from Lake Biwa, a Japanese mesotrophic lake, contained nitrate at concentrations higher than ambient by two to three orders of magnitude. They also accumulated high concentrations of sulfate and abundant elemental sulfur. The results suggest that the Thioploca-specific strategy for sulfur oxidation, migration with accumulated nitrate, is effective even in freshwater habitats of lower sulfide supply.


RNAi of arcRNA hsrω affects sub-cellular localization of Drosophila FUS to drive neurodiseases.
Defective RNA metabolism is common pathogenic mechanisms involved in neurological disorders. Indeed, a conspicuous feature of some neurodegenerative diseases is the loss of nuclear activities of RNA-binding proteins (RBPs) like Fused in sarcoma (FUS) and eventually, their accumulation in cytoplasmic proteinaceous inclusions. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes, including neurological disorders. A subset of these lncRNAs is the core of nuclear bodies (NBs), which are the sites of RNA processing and sequestration of specific ribonucleoproteins (RNPs) complexes. In Drosophila melanogaster the lncRNA hsrω is the architectural RNA (arcRNA) of the NB omega speckles (ω-speckles). Here, we show that the neuron-specific and motor neuron-specific knockdown of hsrω impairs locomotion in larval and adult flies and induces anatomical defects in presynaptic terminals of motor neurons, suggesting a novel role of arcRNA hsrω in development of neuromuscular junctions. Since RBPs are recognized as important regulators of neuronal activities, to examine the molecular mechanism of such neurodegeneration, we analysed interaction between hsrω and Drosophila orthologue of human FUS (dFUS). Strictly, we found that dFUS genetically and physically interacts with the arcRNA hsrω. Moreover, we revealed that a fine regulation of gene expression occurs between hsrω and dFUS and surprisingly, we uncover that depletion of hsrω affects the sub-cellular compartmentalization of dFUS thus, enhancing its cytoplasmic localization and inducing its loss of nuclear function. The model we propose shows the role of arcRNA in diseases affecting the nervous system and in particular it elucidates the molecular mechanism underlying the loss of dFUS nuclear function in the absence of its mutations. Our new findings could provide new insights into the pathogenesis of neurodegenerative disease dependent on mis-function or mis-localization of aggregation prone RNA binding proteins like FUS in Amyotrophic Lateral Sclerosis.


Syndecan-1 in Cancer: Implications for Cell Signaling, Differentiation, and Prognostication.
Syndecan-1, a cell surface heparan sulfate proteoglycan, is critically involved in the differentiation and prognosis of various tumors. In this review, we highlight the synthesis, cellular interactions, and the signalling pathways regulated by syndecan-1. The basal syndecan-1 level is also crucial for understanding the sequential changes involving malignant transformation, tumor progression, and advanced or disseminated cancer stages. Moreover, we focus on the cellular localization of this proteoglycan as cell membrane anchored and/or shed, soluble syndecan-1 with stromal or nuclear accumulation and how this may carry different, highly tissue specific prognostic information for individual tumor types.


Contextual empowerment: the impact of Health Brigade involvement on the women of Miraflor, Nicaragua.
This qualitative, descriptive study investigated how working with Health Brigades influenced a sense of empowerment and a resultant shifting of gender-power relationships for women in a rural Nicaraguan community. A convenience sample of 10 women aged 18 to 65 years who had worked with the Brigades were interviewed. Open and axial coding were used to determine core categories and theoretical concepts. From this emerged a grounded theory of contextual empowerment. Key findings included that within this collectivist culture, the concept of contextual empowerment includes psychosocial and structural dimensions. Implications for nursing practice include the impact of unintentional role modeling.


Efficacy and safety of moxibustion in the treatment of infertility with polycystic ovary syndrome: A protocol of systematic review and meta-analysis.
Polycystic ovary syndrome (PCOS) is one of the common diseases of reproductive endocrine metabolism in gynecology, and it is also a common and difficult disease affecting female reproductive endocrine health. PCOS characterized by insulin resistance and hyperandrogenemia, the clinical manifestations are polychaemia, acne, obesity, infertility, menstrual disorders and so on. Clinical treatment of patients with PCOS ovulatory dysfunction infertility is mainly treated with ovulation-promoting drugs, insulin sensitizer, hyperandrogenemia drugs and other drugs Healing. It is found that the sensitivity of patients to ovulation promotion is poor, and it is often necessary to increase the dosage of drugs to increase ovulation rate, thus increasing the risk of ovarian hyperstimulation syndrome, and the recurrence rate is higher after withdrawal. Moxibustion therapy has shown strong advantages in the treatment of PCOS, and the curative effect is accurate. Therefore, this paper will carry out a systematic evaluation and meta-analysis of the efficacy and safety of moxibustion therapy in the treatment of PCOS. We will search 8 electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database (WF), and Chinese Biomedical Literature Database (CBM). We will search above electronic databases from the beginning to January 2021, without any language restriction. Ovulation rate and pregnancy rate will be accepted as the primary outcomes. The changes of Sex hormone levels, including Luteinizing hormone, follicle-stimulating hormone, serum estradiol, total testosterone will be used as secondary outcomes. RevMan 5.3 software will be used for statistical analysis. The result about the curative effect and safety of moxibustion therapy for PCOS will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. Only when we finish this meta-analysis can we get the result. The results of this study will provide reliable evidence for the efficacy and safety of moxibustion therapy in the treatment of PCOS.


Rewired Metabolism Caused by the Oncogenic Deregulation of MYC as an Attractive Therapeutic Target in Cancers.
MYC is one of the most deregulated oncogenes on multiple levels in cancer. As a node transcription factor, MYC plays a diverse regulatory role in many cellular processes, including cell cycle and metabolism, both in physiological and pathological conditions. The relentless growth and proliferation of tumor cells lead to an insatiable demand for energy and nutrients, which requires the rewiring of cellular metabolism. As MYC can orchestrate all aspects of cellular metabolism, its altered regulation plays a central role in these processes, such as the Warburg effect, and is a well-established hallmark of cancer development. However, our current knowledge of MYC suggests that its spatial- and concentration-dependent contribution to tumorigenesis depends more on changes in the global or relative expression of target genes. As the direct targeting of MYC is proven to be challenging due to its relatively high toxicity, understanding its underlying regulatory mechanisms is essential for the development of tumor-selective targeted therapies. The aim of this review is to comprehensively summarize the diverse forms of MYC oncogenic deregulation, including DNA-, transcriptional- and post-translational level alterations, and their consequences for cellular metabolism. Furthermore, we also review the currently available and potentially attractive therapeutic options that exploit the vulnerability arising from the metabolic rearrangement of MYC-driven tumors.


Clinical trials for polyneuropathy: the role of nerve conduction studies, quantitative sensory testing, and autonomic function testing.
Clinical trials to assess the treatment of diabetic and other forms of polyneuropathy are becoming increasingly common. Nerve conduction studies, quantitative sensory testing, and autonomic function testing are often used in these trials. This article reviews the sensitivity and reproducibility of these measures to detect change in peripheral nerve function during long-term trials. The attributes of nerve conduction studies that are likely to be most useful are summated or averaged sensory nerve action potential amplitudes and averaged motor nerve conduction velocities. Summated or averaged compound muscle action potential amplitude and mean F-wave latencies are also highly informative. Vibratory detection thresholds are sensitive, specific, and highly reproducible for assessment of large myelinated sensory fibers, with cooling and warming detection thresholds also having good sensitivity for small myelinated sensory fibers. Although less well validated for longitudinal trials, visual analogue scale scoring of heat pain provides assessment of unmyelinated sensory fibers. Heart rate variation to deep breathing, Valsalva, or standing are useful to assess cardiac autonomic function. Based on these data that are reviewed and consistent with the conclusions of previous consensus conferences, a combination of these studies is recommended.


[EPIDEMIOLOGICAL CHARACTERISTICS OF TETANUS IN THE REPUBLIC OF CROATIA].
The aim of the study was to determine the epidemiological characteristics of tetanus in Croatia and to determine changes in the age and sex structure, morbidity and mortality after the introduction of mandatory immunization and after the introduction of additional immunization for persons aged ≥ 60. The retrospective study was undertaken and the data on the number of patients and deaths from tetanus in the period 1946–2014 in Croatia were analyzed. The data considering age, gender and geographical location of disease occurrence were also analyzed. The study confirmed the reduction of morbidity, mortality and fatality rate from tetanus after the introduction of mandatory immunization. In the last twenty years the average morbidity rate was 1.68/1 000 000 population. A higher incidence of tetanus was observed in female patients. During the last ten years all patients were in the age group of 60 and above. The distribution of patients according to the geographical location showed a higher incidence of tetanus in continental Croatia (26/31; 84%) than in coastal area. The less reported number occurred during the winter months. This preventive measure is very effective and economically justified.


Non-delaminating Polymer Hydrogel Coatings via C,H-Insertion Crosslinking (CHic) - A Case Study of Poly(oxanorbornenes).
Robust, non-delaminating polymer coatings and hydrogels are needed for technical and biomedical applications. This study focusses on surface-attached poly(oxanorbornene) hydrogels obtained by simultaneous UV-activated crosslinking and surface-immobilization. The synthesis and copolymerization of two oxanorbornene monomers carrying the UV-crosslinkers malonic acid diazoester or benzophenone, which can both undergo UV-triggered C,H-insertion crosslinking (CHic), is presented. The crosslinking efficiency and network stability of hydrogels made from these self-crosslinkable polymers are studied and compared to the properties of poly(oxanorbornene) networks obtained by UV-triggered thiol-ene-reactions involving a low molecular weight crosslinker. Smooth, defect-free, non-delaminating hydrogel coatings were obtained by CHic, not only on laboratory model surfaces but also on a technical product.


Prevalence, clinical phenotype, and outcomes associated with normal B-type natriuretic peptide levels in heart failure with preserved ejection fraction.
B-type natriuretic peptide (BNP) is used widely to exclude heart failure (HF) in patients with dyspnea. However, most studies of BNP have focused on diagnosing HF with reduced ejection fraction (EF). The aim of this study was to test the hypothesis that a normal BNP level (≤100 pg/ml) is relatively common in HF with preserved EF (HFpEF), a heterogenous disorder commonly associated with obesity. A total of 159 consecutive patients enrolled in the Northwestern University HFpEF Program were prospectively studied. All subjects had symptomatic HF with EF >50% and elevated pulmonary capillary wedge pressure. BNP was tested at baseline in all subjects. Clinical characteristics, echocardiographic parameters, invasive hemodynamics, and outcomes were compared among patients with HFpEF with normal (≤100 pg/ml) versus elevated (>100 pg/ml) BNP. Of the 159 patients with HFpEF, 46 (29%) had BNP ≤100 pg/ml. Subjects with normal BNP were younger, were more often women, had higher rates of obesity and higher body mass index, and less commonly had chronic kidney disease and atrial fibrillation. EFs and pulmonary capillary wedge pressures were similar in the normal and elevated BNP groups (62 ± 7% vs 61 ± 7%, p = 0.67, and 25 ± 8 vs 27 ± 9 mm Hg, p = 0.42, respectively). Elevated BNP was associated with enlarged left atrial volume, worse diastolic function, abnormal right ventricular structure and function, and worse outcomes (e.g., adjusted hazard ratio for HF hospitalization 4.0, 95% confidence interval 1.6 to 9.7, p = 0.003). In conclusion, normal BNP levels were present in 29% of symptomatic outpatients with HFpEF who had elevated pulmonary capillary wedge pressures, and although BNP is useful as a prognostic marker in HFpEF, normal BNP does not exclude the outpatient diagnosis of HFpEF.


Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients.
A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial. Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined. A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase. Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.


[Screening of pyrene degradation bacteria strain from the Kochia scoparia roots and its potential for promoting growth].
The endophytic bacteria were isolated from the roots of polycyclic aromatic hydrocarbon (PAHs)-tolerant plant. We investigated their ability of PAHs degradation and plant growth promo-ting, with the aim to provide theoretical support for bacterial-plant cooperative soil remediation. Kochia scoparia living in coking plant area were selected for strains isolation. Eight endophytic bacteria strains, which used pyrene and 1-aminocyclopropane-1-carboxylic acid (ACC) as sole carbon and nitrogen source, were isolated from the roots of K. scoparia. Three endophytic bacteria, KSE4, KSE7 and KSE8, displayed high degradation efficiency in pyrene degradation experiment. They were identified as Bacillus sp., Pseudomonas sp., and Sphingobacterium sp., respectively. The abili-ties of those three strains to produce ACC deaminase and their effects on seed germination of K. scoparia were examined under pyrene stress through liquid culture tests. The results showed that the activity of ACC deaminase decreased with increasing pyrene concentration (0-15 mg·L-1). KSE7 had the strongest promotion effect. When pyrene concentration reached to 15 mg·L-1, the germination rate and bud length of K. scoparia increased by 44.8% and 61.1%, respectively. Our results indicated that KSE7 is a promising bacterial strain for soil remediation in coking plant area.


Sudden Infant Death Syndrome: Risk Factors and Newer Risk Reduction Strategies.
Sudden infant death syndrome (SIDS) continues to be one of the top causes of infant death in the U.S. Despite significant public health initiatives focused on high-risk populations to enhance sleep environments and techniques. The SIDS rate has remained stable in recent years. Risk factors and newer risk reduction strategies for SIDS are the focus of this review article. We conducted a comprehensive literature search on Medline, Cochrane, Embase, and Google Scholar until July 2022. The following search strings and Medical Subject Heading (MeSH) terms were used: "SIDS," "Sudden Infant Death" and "SUID". We explored the literature on SIDS for its epidemiology, pathophysiology, the role of various etiologies and their influence, associated complications leading to SIDS, and preventive and treatment modalities. Despite a more than 50% drop-in rates since the start of the "Back to Sleep" campaign in 1994, sudden infant death syndrome (SIDS) continues to be the top cause of post-neonatal mortality in the United States, despite continued educational initiatives that support safe sleep and other risk reduction strategies. The new American Academy of Pediatrics guidelines for lowering the risk of SIDS include a lot of emphasis on sleeping habits, bedding, and environment but also include elements that are frequently ignored (i.e., prenatal care, smoking, alcohol and drug use, and childhood vaccinations). This study highlights these less-frequently discussed aspects and identifies treatments that have produced beneficial behavioral shifts that benefit newborns as well as their mothers' health and wellbeing.


Erythropoietin gene expression in vitro and in vivo detected by in situ hybridization.
Macrophages derived from unstimulated and unseparated mouse bone marrow cells have been shown to release erythropoietin into the extracellular fluid. Additional proof that macrophages can produce the hormone would be a demonstration that the gene is expressed and the mature protein released. In situ hybridization using a 1.2 kb biotinylated erythropoietin DNA probe demonstrates that both cultured macrophages and those present in normal mouse bone marrow express the gene. These results are discussed in terms of the role played by the macrophage in the hemopoietic cellular microenvironment and indicate that a subpopulation is responsible for this function and that cell interactions play an important role in hemopoietic differentiation.


[Head and neck cancers in HIV patients].
Among HIV-infected patients, head and neck cancer incidence has increased over the last few years. Head and neck cancer treatment in HIV-infected patients does not differ from the general population but those patients are exposed more frequently to radiation severe toxic effects and need close monitoring during chemoradiotherapy treatment. Close cooperation between oncologist and infectiologist is crucial to eventually adjust antiretroviral therapy. Like general population, HIV-infected patients should be advised to avoid excessive alcohol consumption and tobacco smoking.


High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients.
The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients. As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months. In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.


Deep Convolutional Neural Network With Adversarial Training for Denoising Digital Breast Tomosynthesis Images.
Digital breast tomosynthesis (DBT) is a quasi-three-dimensional imaging modality that can reduce false negatives and false positives in mass lesion detection caused by overlapping breast tissue in conventional two-dimensional (2D) mammography. The patient dose of a DBT scan is similar to that of a single 2D mammogram, while acquisition of each projection view adds detector readout noise. The noise is propagated to the reconstructed DBT volume, possibly obscuring subtle signs of breast cancer such as microcalcifications (MCs). This study developed a deep convolutional neural network (DCNN) framework for denoising DBT images with a focus on improving the conspicuity of MCs as well as preserving the ill-defined margins of spiculated masses and normal tissue textures. We trained the DCNN using a weighted combination of mean squared error (MSE) loss and adversarial loss. We configured a dedicated x-ray imaging simulator in combination with digital breast phantoms to generate realistic in silico DBT data for training. We compared the DCNN training between using digital phantoms and using real physical phantoms. The proposed denoising method improved the contrast-to-noise ratio (CNR) and detectability index (d') of the simulated MCs in the validation phantom DBTs. These performance measures improved with increasing training target dose and training sample size. Promising denoising results were observed on the transferability of the digital-phantom-trained denoiser to DBT reconstructed with different techniques and on a small independent test set of human subject DBT images.


[Leiomyosarcoma of the stomach].
A case of gastric leiomyosarcoma (primary maliganant mesenchymal neoplasia of non-lymphoblastic origin) personally observed, is presented. The pathological anatomy, aetiopathogensis, symptomatology and diagnosis of this disease are described as well as the surgical treatment of the case.


Clinical value of miR-145-5p in NSCLC and potential molecular mechanism exploration: A retrospective study based on GEO, qRT-PCR, and TCGA data.
MicroRNAs have been reported to be involved in various biological processes. Here, we performed a systematic analysis to explore the clinical value and potential molecular mechanism of miR-145-5p in non-small cell lung cancer. First, a meta-analysis was performed with eligible literature, followed by microRNA microarrays in the Gene Expression Omnibus database, to verify the diagnostic and prognostic values of miR-145-5p. A cohort of 125 clinical paired non-small cell lung cancer samples was next used to detect the level of miR-145-5p and to explore the relationship of miR-145-5p with clinicopathological parameters. The Cancer Genome Atlas database was additionally applied to investigate the role of miR-145-5p in non-small cell lung cancer. The potential targets of miR-145-5p were predicted using 12 online prediction databases to explore the prospective molecular mechanism of miR-145-5p in non-small cell lung cancer. The expression of miR-145-5p in non-small cell lung cancer was significantly lower than that in healthy tissues. And miR-145-5p tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma. Furthermore, the expression of miR-145-5p was closely associated with lymph node metastasis in non-small cell lung cancer. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched with enzyme-linked receptor protein signaling pathways, SH3 domain binding, cell leading edge, and adherens junction. The protein-protein interaction network showed that eight hub genes (SMAD4, SMAD2, IRS1, FOXO1, ERBB4, NRAS, ACTB, and ACTG1) might be the key target genes of miR-145-5p in non-small cell lung cancer. The information we obtained might offer new perspectives for clinical diagnosis and treatment for non-small cell lung cancer.


Massive hemoperitoneum due to a ruptured corpus luteum cyst in a patient with congenital hypofibrinogenemia.
Congenital afibrinogenemia/hypofibrinogenemia is a rare inherited hematologic disorder in which a patient lacks or has insufficient level of fibrinogen, the blood coagulation factor I. The incidence of this uncommon disease is 1 to 2 per 1 million individuals. Hence, massive hemoperitoneum caused by ovulation in a woman with congenital afibrogenemia is also a very rare clinical condition. Massive hemoperitoneum usually presents as acute abdominal pain with potential findings of peritonitis including abdominal distention, hypotension and tachycardia with critical consequences. We performed emergent endoscopic surgery for hemoperitoneum caused by a ruptured corpus luteum cyst in a patient with congenital hypofibrinogenemia. To the best of our knowledge, this was the first case report of such treatment in Korea.


Prostate cancer abdominal metastases detected with indium-111 capromab pendetide.
To provide appropriate therapy for prostate cancer, accurate staging of the patient's disease is essential. Determination of tumor size, location, periprostatic extension and metastatic disease in the skeleton and soft tissue are needed to stage properly. Current diagnostic modalities may lead to understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both at the time of initial diagnosis and in patients with suspected local recurrence, can significantly alter the type of therapy given. Clinical studies using the (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab pendetide), have shown the superiority of radioimmunoscintigraphy over other diagnostic modalities in the detection of both primary and metastatic prostate cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of tumor-associated antigen rather than lesion size. Earlier detection of extraprostatic invasion and metastases by means of radioimmunoscintigraphy provides valuable information for treatment decisions. A case of metastatic prostate cancer in the abdomen of a patient without local disease, in which the extent of disease was confirmed at autopsy after sudden cardiac arrest, is presented.


Visceral tissue vascularization: an adaptive response to high temperature.
Electrical heat sources implanted in the abdominal cavities of sheep were heated to give initial temperatures of 42 degrees and 45 degrees C at the surfaces of the heaters. During 18 days of constant heating, a vascularized connective-tissue envelope encapsulated the heat sources, and the temperatures at the surfaces of the heaters declined 0.8 degrees and 1.8 degrees C, respectively. The degree of vascularization and the magnitude of the decrease in the surface temperature appeared to be related to the proximity of the tissue's initial temperature to 45 degrees C, a temperature ordinarily considered detrimental to cell structure. The vascularization thus appears to be adaptive.


Structure of the catalytic chain of Methanococcus jannaschii aspartate transcarbamoylase in a hexagonal crystal form: insights into the path of carbamoyl phosphate to the active site of the enzyme.
Crystals of the catalytic chain of Methanococcus jannaschii aspartate transcarbamoylase (ATCase) grew in the presence of the regulatory chain in the hexagonal space group P6(3)22, with one monomer per asymmetric unit. This is the first time that crystals with only one monomer in the asymmetric unit have been obtained; all known structures of the catalytic subunit contain several crystallographically independent monomers. The symmetry-related chains form the staggered dimer of trimers observed in the other known structures of the catalytic subunit. The central channel of the catalytic subunit contains a sulfate ion and a K(+) ion as well as a glycerol molecule at its entrance. It is possible that it is involved in channeling carbamoyl phosphate (CP) to the active site of the enzyme. A second sulfate ion near Arg164 is near the second CP position in the wild-type Escherichia coli ATCase structure complexed with CP. It is suggested that this position may also be in the path that CP takes when binding to the active site in a partial diffusion process at 310 K. Additional biochemical studies of carbamoylation and the molecular organization of this enzyme in M. jannaschii will provide further insight into these points.


Hash-MAC-DSDV: Mutual Authentication for Intelligent IoT-Based Cyber-Physical Systems.
Cyber-Physical Systems (CPS) connected in the form of Internet of Things (IoT) are vulnerable to various security threats, due to the infrastructure-less deployment of IoT devices. Device-to-Device (D2D) authentication of these networks ensures the integrity, authenticity, and confidentiality of information in the deployed area. The literature suggests different approaches to address security issues in CPS technologies. However, they are mostly based on centralized techniques or specific system deployments with higher cost of computation and communication. It is therefore necessary to develop an effective scheme that can resolve the security problems in CPS technologies of IoT devices. In this paper, a lightweight Hash-MAC-DSDV (Hash Media Access Control Destination Sequence Distance Vector) routing scheme is proposed to resolve authentication issues in CPS technologies, connected in the form of IoT networks. For this purpose, a CPS of IoT devices (multi-WSNs) is developed from the local-chain and public chain, respectively. The proposed scheme ensures D2D authentication by the Hash-MAC-DSDV mutual scheme, where the MAC addresses of individual devices are registered in the first phase and advertised in the network in the second phase. The proposed scheme allows legitimate devices to modify their routing table and unicast the one-way hash authentication mechanism to transfer their captured data from source towards the destination. Our evaluation results demonstrate that Hash-MAC-DSDV outweighs the existing schemes in terms of attack detection, energy consumption and communication metrics.


Flavonoids from Koelreuteria henryi and other sources as protein-tyrosine kinase inhibitors.
The EtOH extract of Koelreuteria henryi was investigated in a search for natural products with potential protein-tryrosine kinase (PTK) inhibitory activity. The PTK inhibitory activity of the crude fractions was determined by measuring their inhibition of p56lck partially purified from bovine thymus using angiotensin I as a substrate. Analysis of those fractions that exhibited significant activity led to the isolation of kaempferol and quercetin, in addition to two kaempferol glycosides, kaempferol-O3-alpha-rhamnopyranoside [1] and kaempferol-O3-alpha-arabinopyranoside [2]. This study represents the first report on the isolation of flavonols and their PTK inhibitory activities from the genus Koelreuteria. Eight other flavonoids were also examined to study the role of the hydroxy groups on the B ring on PTK inhibitory activity.


ROLE OF SPOUSAL INVOLVEMENT IN CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) ADHERENCE IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA (OSA).
Little is known about the impact of spousal involvement on continuous positive airway pressure (CPAP) adherence. The aim of this study was to determine whether spouse involvement affects adherence with CPAP therapy, and how this association varies with gender. 194 subjects recruited from Apnea Positive Pressure Long Term Efficacy Study (APPLES) completed the Dyadic Adjustment Scale (DAS). The majority of participants were Caucasian (83%), and males (73%), with mean age of 56 years, mean BMI of 31 kg/m2. & 62% had severe OSA. The DAS is a validated 32-item self-report instrument measuring dyadic consensus, satisfaction, cohesion, and affectional expression. A high score in the DAS is indicative of a person's adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked. CPAP use was downloaded from the device and self-report, and compliance was defined as usage ≥ 4 h per night. There were no significant differences in overall marital quality between the compliant and noncompliant subjects. However, level of spousal involvement was associated with increased CPAP adherence at 6 months (p=0.01). After stratifying for gender these results were significant only among males (p=0.03). Three years after completing APPLES, level of spousal involvement was not associated with CPAP compliance even after gender stratification. Spousal involvement is important in determining CPAP compliance in males in the 1st 6 months after initiation of therapy but is not predictive of longer-term adherence. Involvement of the spouse should be considered an integral part of CPAP initiation procedures. HL068060.


Molecular epidemiology and drug resistance of Mycobacterium tuberculosis isolates from Ethiopian pulmonary tuberculosis patients with and without human immunodeficiency virus infection.
We have analyzed the molecular epidemiology and drug resistance of 121 Mycobacterium tuberculosis isolates from consecutive patients with culture-positive pulmonary tuberculosis attending a university hospital outpatient department in Addis Ababa, Ethiopia. Restriction fragment length polymorphism analysis and spoligotyping were used to analyze the DNA fingerprinting patterns. Fifty-one (41.2%) of the isolates were found in 13 clusters with two or more identical DNA patterns. Two such clusters contained 49.0% of all clustered isolates. In a multivariate logistic regression model, human immunodeficiency virus (HIV)-positive serostatus was significantly associated with clustering of isolates for patients of both sexes (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.17 to 5.80). There was a trend toward increased clustering of isolates from tuberculous women residing in Addis Ababa (OR, 2.10; 95% CI, 0.85 to 5.25). In total, 17 of 121 isolates (14.0%) were resistant to one or more of the antituberculosis drugs isoniazid (8.3%), streptomycin (7.4%), rifampin (2.5%), and ethambutol (1.7%). The high rate of drug-resistant isolates (29.6%) coincided with the peak prevalence of HIV infection (77.8%) in patients 35 to 44 years old. The majority (62.5%) of resistant isolates in this group were found within clusters. The simultaneous accumulation of certain bacterial clones in a patient population likely reflects recent transmission. Hence, we conclude that tuberculosis is commonly caused by recent infection with M. tuberculosis in HIV-positive Ethiopian patients. Furthermore, with the rapidly increasing prevalence of HIV infection in Ethiopia, the burden of tuberculosis, including drug-resistant tuberculosis, is likely to increase. Strengthening of classical tuberculosis control measures by promoting active case finding among HIV-positive adults with tuberculosis is warranted to reduce rates of transmission.


Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis.
Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-gamma. The role of these cytokines in the pathogenesis of AD is not known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-gamma cytokine genes to assess the role of these cytokines in this model.OVA-sensitized skin from IL-5(-/-) mice had no detectable eosinophils and exhibited decreased epidermal and dermal thickening. Sensitized skin from IL-4(-/-) mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells. These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1beta, and RANTES. Sensitized skin from IFN-gamma-/- mice was characterized by reduced dermal thickening. These results suggest that both the TH2 cytokines IL-4 and IL-5 and the TH1 cytokine IFN-gamma play important roles in the inflammation and hypertrophy of the skin in AD.