Long-term metabolic effects of truncal vagotomy and gastrojejunostomy for chronic duodenal ulcer.
In a review of 305 consecutive patients who had undergone truncal vagotomy and gastrojejunostomy for duodenal ulceration 5-15 (mean 10.5) years before, symptomatic and metabolic sequelae were related to a dietary survey in 109 patients. The incidence of post vagotomy symptoms was related to the incidence of weight loss and reduced dietary energy intake. The dietary survey did not show any trends in the incidence of weight loss since operation. Biochemical steatorrhoea occurred in 48% of 96 patients, but this was not related to dietary fat intake, or to weight loss unless diarrhoea was also present. Anaemia was noted in 13% of patients, but the incidence was not related to dietary survey, age, symptoms or post-vagotomy gastric acid output.


Electrosorption capacitance of nanostructured carbon-based materials.
The fundamental mechanism of electrosorption of ions developing a double layer inside nanopores was studied via a combination of experimental and theoretical studies. A novel graphitized-carbon monolithic material has proven to be a good electrical double-layer capacitor that can be applied in the separation of ions from aqueous solutions. An extended electrical double-layer model indicated that the pore size distribution plays a key role in determining the double-layer capacitance in an electrosorption process. Because of the occurrence of double-layer overlapping in narrow pores, mesopores and micropores make significantly different contributions to the double-layer capacitance. Mesopores show good electrochemical accessibility. Micropores present a slow mass transfer of ions and a considerable loss of double-layer capacitance, associated with a shallow potential distribution inside pores. The formation of the diffuse layer inside the micropores determines the magnitude of the double-layer capacitance at low electrolyte concentrations and at conditions close to the point of zero charge of the material. The effect of the double-layer overlapping on the electrosorption capacitance can be reduced by increasing the pore size, electrolyte concentration, and applied potential. The results are relevant to water deionization.


4-(Di-phenyl-meth-oxy)-3-eth-oxy-benzaldehyde.
In the title compound, C22H20O3, the dihedral angle between the aromatic rings linked by the methine group is 81.265 (4)° and the eth-oxy side chain adopts an extended conformation [C-O-C-C = 177.24 (10)°]. In the crystal, weak C-H⋯π and C-H⋯O inter-actions link the mol-ecules into sheets.


An approach to local immunotoxicity induced by adjuvanted vaccines.
The occurrence of injection site reactions following immunization is the most frequently reported toxicity manifestation of vaccines; however, the different types of local reactions and the different mechanisms involved are still unclear. Here, the current advances in adjuvants and the role that adjuvants play in local reactions are reviewed. The role of adjuvants in the formation of the loco-regional complex (LRC), which consists of the injection site, draining lymphatic vessels and regional lymph nodes, is also discussed. Finally, strategies and recommendations for the rational design of adjuvanted vaccines are discussed, with a particular interest in the reduction of local inflammation.


Bilateral symmetry embedded in noise is detected accurately only at fixation.
Bilateral or mirror symmetry is a ubiquitous feature of biological forms that the visual system could exploit for segmenting an object from a cluttered background. If this is so, the visual system may be prepared to detect symmetry at all retinal locations in parallel. Indeed, a biologically plausible model that responds optimally at axes of symmetry is quite easy to construct. Our data show, however, that if such a mechanism exists, it works with high efficiency only at the fovea. The detection of vertical bilateral symmetry embedded in random noise is very poor unless the axis of symmetry is very close to the point of fixation. This leads to the conclusion that symmetry does not play an important role in image segmentation and that it is important to the visual system only after it is fixated.


Effect of carboxymethyl groups on degradation of modified pullulan by pullulanase from Klebsiella pneumoniae.
Pullulanase is an enzyme that hydrolyses the α-1,6 linkages of pullulan (Pull) to produce maltotriose units. We studied the capacity of pullulanase to cleave its modified substrate: carboxymethylpullulan (CMPull), synthesized with two different degrees of substitution (DS=0.16 and 0.8). Size exclusion chromatography with on line multi angle light scattering and differential refractive index detection (SEC/MALS/DRI) was used to estimate both number and weight average molar masses, respectively, Mn and Mw, of pullulan and CMPulls together with the percentage of maltotriose formed during hydrolysis. Determination of reduced sugars gave also a Mn that is compared to data obtained by SEC. It revealed that CMPull is partially degraded by pullulanase and the rate of hydrolysis decreased with increased DS. At the end of the hydrolysis, Mn is decreased by a factor of 23 and 1.7 for CMPull with a DS of 0.16 and 0.8 respectively. The percentage of produced maltotriose decreased also when increasing DS (24% and 7% for CMPull DS 0.16 and 0.8 respectively). The kinetic properties of pullulanase were also investigated with Pull and CMPulls by isothermal titration calorimetry (ITC) using simple injection method. Based on Michaelis-Menten kinetics, Vmax (maximal velocity) decreased and KM (Michaelis constant) increased when DS of modified pullulan CMPull increased.


The polishability of posterior composites.
The polishability of six brands of posterior composites was evaluated by means of a stylus profile instrumentation and scanning electron microscopy and was compared with that of an anterior microfilled composite. A sedigraphic study was performed to estimate the size and distribution of their inorganic particles. The extent of the filler loading as well as the hardness values were also assessed to determine any relevant characteristics. Some of the findings indicated that posterior composites with large particles produced significantly higher surface roughness than those with small fiber particles. A direct correlation was also found between the hardness value and surface roughness value, indicating that a composite with higher hardness value yielded a higher roughness value.


Hot boning of intact carcasses: a procedure to avoid central nervous system self-contamination in beef and beef products.
Compared with traditional boning of split refrigerated carcasses, hot boning of intact carcasses (the removal of meat from the skeleton prerigor) provides several commercially important cuts, may improve quality and reduce refrigeration costs, and may reduce the contamination of carcasses with central nervous system (CNS) tissue. In a comparative study of hot boning of intact and split carcasses, the CNS tissue contamination of intact carcasses was negligible (as measured with the CNS-related proteins glial fibrillary acidic protein and S-100 protein), but split carcasses were highly contaminated. The same trends were observed for dissection worktables used during the boning process. Most current boning plants have processing lines that are organized for boning carcass quarters, where the carcasses, in addition to transversal division, also are split horizontally. This part of the boning process was incorporated in the design of our study. Nine of the 18 intact carcasses were split horizontally between thoracic vertebrae 10 and 11 before they were hot boned. CNS tissue contamination was not detected on the carcass site related to this procedure. The amount of CNS tissue contamination was similar in boned cuts and minced meat from split and intact carcasses, except in the forerib. Boning of split carcasses appears to reduce CNS tissue contamination significantly to a level comparable to that of intact hot-boned carcasses.


Protective effects of a selective L-type voltage-sensitive calcium channel blocker, S-312-d, on neuronal cell death.
Amyloid beta protein (Abeta)- and human group IIA secretory phospholipase A(2) (sPLA(2)-IIA)-induced neuronal cell death have been established as in vitro models for Alzheimer's disease (AD) and stroke. Both sPLA(2)-IIA and Abeta causes neuronal apoptosis by increasing the influx of Ca(2+) through L-type voltage-sensitive Ca(2+) channel (L-VSCC). In the present study, we evaluated effects of a selective L-VSCC blocker, S-(+)-methyl 4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitro-phenyl)thieno[2,3-b]pyridine-5-carboxylate (S-312-d), on Abeta- and sPLA(2)-IIA-induced neuronal apoptosis in primary cultures of rat cortical neurons. S-312-d significantly rescued cortical neurons from Abeta- and sPLA(2)-IIA-induced cell death. Both cell death stimuli caused the appearance of apoptotic features such as plasma membrane blebs, chromatin condensation, and DNA fragmentation. S-312-d completely suppressed these apoptotic features. Before apoptosis, the two death ligands markedly enhanced an influx of Ca(2+) into neurons. S-312-d significantly prevented neurons from sPLA(2)-IIA- and Abeta-induced Ca(2+) influx. Furthermore, the neuroprotective effect of S-312-d was more potent than that of another L-VSCC blocker, nimodipine. On the other hand, blockers of other VSCCs such as the N-type and P/Q-type calcium channels had no effect on the neuronal cell death, apoptotic features and Ca(2+) influx. In conclusion, we demonstrated that S-312-d rescues cortical neurons from Abeta- and sPLA(2)-IIA-induced apoptosis.


Optimising the selection of outcomes for healthy ageing trials: a mixed methods study.
Advancing age is associated with chronic diseases which are the largest cause of death and disability in developed countries. With increasing life expectancy and an ageing population, there is a need to conduct trials to extend healthy ageing, including targeting biological ageing processes, and prevent ageing-related diseases. The main objectives of the study are as follows: (i) to review outcome measures utilised in healthy ageing trials focusing on pharmacological therapies, nutritional supplements and medical devices; (ii) to summarise the views of key stakeholders on outcome selection for healthy ageing trials. An analysis of records from the Clinicaltrials.gov database pertaining to healthy ageing trials from inception to May 2022 was conducted. In addition, the findings of a workshop attended by key stakeholders at the 2022 annual UKSPINE conference were qualitatively analysed. Substantial heterogeneity was found in the interventions evaluated and the outcomes utilised by the included studies. Recruitment of participants with diverse backgrounds and the confounding effects of multi-morbidity in older adults were identified as the main challenges of measuring outcomes in healthy ageing trials by the workshop participants. The development of a core outcome set for healthy ageing trials can aid comparability across interventions and within different settings. The workshop provided an important platform to garner a range of perspectives on the challenges with measuring outcomes in this setting. It is critical to initiate such discussions to progress this field and provide practical answers to how healthy ageing trials are designed and structured in the future.


Exercise Interventions for Improving Flexibility in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.
Background and objectives: People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of this study was to conduct a systematic review and a meta-analysis aimed at identifying the characteristics and methodological quality of investigations studying the effects of exercise interventions on the flexibility levels of people with MS. Materials and Methods: Three electronic databases (MEDLINE/PubMed, SPORTDiscus and Scopus) were systematically searched up to May 2019 for intervention studies focused on the effects of exercise on the flexibility levels of people with MS. A meta-analysis, including randomized controlled trials (RCT), which reported information regarding the effects of exercise on flexibility, was also conducted. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database, and the Quality Assessment Tool for Before-After Studies, with no control group. The quality of the information reported, regarding the programs conducted, was assessed by means of the Consensus on Exercise Reporting Template (CERT) scale. Results: Seven studies, four RCTs and three uncontrolled investigations were finally selected. The methodological quality of the RCTs was considered "poor" in one study, and "good" and "excellent" in two studies and one investigation, respectively. The three uncontrolled studies showed a methodological quality between "fair" and "poor". Following the CERT scale, four studies were graded as "high" and three as "low". Findings from the meta-analysis indicated no significant effects on hamstring flexibility, or the range of motion in the hips, knees or ankles. Conclusions: There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following participation in physical exercise programs, but the meta-analysis did not confirm these findings.


The 4S binding protein acts as a trans-regulator of the polycyclic hydrocarbon-inducible cytochrome P450.
A model has been proposed for the induction of cytochrome P450c in liver by polycyclic hydrocarbons such as benzo(a)pyrene (BaP) and 3-methylcholanthrene (3MC). The polycyclic hydrocarbon interacts in specific, saturable, and high-affinity fashion with a rat liver cytosolic 4s binding protein. The latter enters the nucleus, complexes to 5' upstream regions of the cytochrome P450c gene, and stimulates the transcription. The 4s binding protein has been purified from rat liver and its substrate specificity has been determined. The affinity for 3MC or BaP is 1-2 mM. The binding protein has been demonstrated to complex with specific 5'-upstream regions of the P450c gene by using a filtration assay as well as exonuclease footprinting. In addition, the binding protein stimulates in vitro transcription with upstream regions of the P450c gene as template; these data confirm the hypotheses.


Cross-sectional dietary deficiencies among a prison population in Papua New Guinea.
To investigate the dietary adequacy of prisoners of Beon Prison, Madang, Papua New Guinea in response to a report of possible nutritional deficiency. We undertook an observational, cross-sectional study. All 254 male inmates (May 2010) were eligible to answer a validated interview-based questionnaire; to have a comprehensive dietary assessment; and to provide blood for biochemical analysis (α-tocopherol, β-carotene, lutein, thiamin, riboflavin, niacin, folate, homocysteine, zinc, ferritin, and vitamins A, B12 and C). Prison guards were invited to participate as a comparison group. 148 male prisoners (58.3%) and 13 male prison guards participated. Prison rations consisted of white rice fortified with thiamin, niacin, and iron, tinned tuna, tinned corned beef, water crackers, and black tea, with occasional intakes of fruit and vegetables. Some prisoners received supplementary food from weekend visitors. From assessment of the prisoners dietary data, median intakes of calcium (137 mg), potassium (677 mg), magnesium (182 mg), riboflavin (0.308 mg), vitamin A (54.1 μg), vitamin E (1.68 mg), vitamin C (5.7 mg) and folate (76.4 μg) were found to be below estimated average requirements (EAR). The prisoners diets are likely lacking in several micronutrients and recommendations for dietary change have been made to the prison authorities. Ongoing vigilance is required in prisons to ensure the basic human right of access to a nutritionally adequate diet is being observed.


A mini-invasive surgical technique for Carlevale IOL implantation: case series study and description of concomitant surgery.
To examine the feasibility and outcomes of a modified technique for the implantation of scleral fixated Carlevale intraocular lens (IOL) (I71 FIL SSF. Soleko IOL Division, Pontecorvo, Italy), and to analyze the occurrence of adverse events. This is a retrospective observational study conducted revising patients charts from 2018 to 2023. Thirty-five eyes of 33 patients were included. Patients requiring IOL explantation had either IOL dislocation or opacification. The implantation of the Carlevale IOL was performed with the subconjunctival positioning of the anchors without any scleral flap. All maneuvers were performed transconjunctivally. The anatomical outcomes considered were IOL positioning, and the absence of postoperative complications. The functional outcomes analyzed were best correctedvisual acuity (BCVA) and refraction. In all the cases, the IOL was well positioned and centered postoperatively. No cases of conjunctival erosion were recorded. The best corrected visual acuity (BCVA) was 0.9±0.6 logMar (mean±standard deviation) preoperatively and 0.5±0.5 logMar (mean±standard deviation) postoperatively. The mean preoperative spherical equivalent was +6.8±7.7 dioptres, while postoperatively it was -1.1±1.6 dioptres. The most frequent procedure associated to secondary IOL implantation was posterior vitrectomy (25 eyes, 71.4%), which was performed with 25-gauge transconjunctival cannulas in the ciliary sulcus. The follow-up period was 24.5±16.9 months (mean±standard deviation). The described mini-invasive technique for Carlevale IOL implantation is safe and effective. It can be recommended either as a stand-alone operation or associated to concurrent surgical procedures.


Current and emerging pharmacological treatments for respiratory syncytial virus infection in high-risk infants.
The human respiratory syncytial virus (hRSV) is the leading cause of respiratory infections in children, older adults, and patients with comorbidities. Since the hRSV discovery, multiple efforts have been made to generate therapies that control the devastating effects on the population at risk in winter. This article describes the development of different drugs and treatments approved for use in the risk-population against hRSV infection. In addition, an exhaustive bibliographical review is presented here describing new candidate molecules under evaluation and showing promising results in different assays in animal models and clinical studies. Additionally, we highlight antiviral molecules, monoclonal antibodies, and nanobodies among the new candidate treatments. hRSV is a major burden for the health systems, promoting their collapse worldwide. Therefore, developing new therapies is an essential goal to decrease hospitalization rates caused by hRSV infection in high-risk populations. For this, injecting resources and exploring new targets in addition to the F protein is an interesting alternative to achieve this goal.


A functional genomic study on NCI's anticancer drug screen.
Pharmacogenomics requires massive computer exploration on heterogeneous databases. COMPARE, the gateway to the NCI's anticancer drug screen database, allows users to correlate drug-sensitivity profiles with a functional genomic database. However, most drugs of known molecular mechanism turn out to be uncorrelated with their molecular-target gene expression. Based on a novel statistical concept, liquid association, we develop an on-line system to identify candidate genes that intervene, confound and weaken the drug-gene correlation. The system takes queries and returns button-clickable tables of functionally associated genes for rerouting to knowledgebases such as Locus Link, OMIM and PubMed. We report results that link methotrexate resistance to DNA component biosynthesis, and taxol sensitivity to genes associated with human immunodeficiency virus infection. The drug-sensitivity database can be synergistically coanalyzed with gene expression data to study proteins of poorly understood physiological roles. When applied to the human prion, a cellular context embroidered with the gene expression network of Alzheimer disease is revealed.


Transcriptional response of human microglial cells to interferon-gamma.
Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-gamma, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-gamma signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-gamma induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia-T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-gamma-a key to understanding cell-mediated immunity of the CNS.


DIAGNOSTIC Classification Analysis of Problem-Solving Competence using Process Data: An Item Expansion Method.
Process data refer to data recorded in computer-based assessments (CBAs) that reflect respondents' problem-solving processes and provide greater insight into how respondents solve problems, in addition to how well they solve them. Using the rich information contained in process data, this study proposed an item expansion method to analyze action-level process data from the perspective of diagnostic classification in order to comprehensively understand respondents' problem-solving competence. The proposed method cannot only estimate respondents' problem-solving ability along a continuum, but also classify respondents according to their problem-solving skills. To illustrate the application and advantages of the proposed method, a Programme for International Student Assessment (PISA) problem-solving item was used. The results indicated that (a) the estimated latent classes provided more detailed diagnoses of respondents' problem-solving skills than the observed score categories; (b) although only one item was used, the estimated higher-order latent ability reflected the respondents' problem-solving ability more accurately than the unidimensional latent ability estimated from the outcome data; and (c) interactions among problem-solving skills followed the conjunctive condensation rule, which indicated that the specific action sequence appeared only when a respondent mastered all required problem solving skills. In conclusion, the proposed diagnostic classification approach is feasible and promising analyzing process data.


[Improvement of arteriography technics by new thin catheters].
New, small, polyurethane French 4 and French 5 sized catheters with a commensurately large lumen are described. In combination with DSA they allow low doses of contrast media in renal insufficiency and facilitate selective and superselective manipulations. The high flow specification also permits use in "conventional" angiography.


[Facultative wound myiasis of man in Austria (author's transl)].
Three cases of contingent wound myiasis (traumatic myiasis) in man in Austria caused by Lucilia sericata (2 cases) and Sarcophaga argyrostoma and Lucilia sericata (1 case) are reported.


Sliding Sign and Gel Sonovaginography: A Sneak Peek Prior to Laparoscopy in Patients with Endometriosis.
The rising incidence of endometriosis may be due to improvisation in the diagnostic techniques. Transvaginal sonography has proven to be very useful in the diagnosis of complexity of the disease and in turn to predict the intraoperative findings on laparoscopy. The aim was to study the use of sliding sign for detecting the status of the pouch of Douglas (POD) and to check for the presence of bowel and nonbowel deep infiltrating endometriosis (DIE) by gel sonovaginography. This is a prospective observational study carried out patient division of Department of OBG in Kasturba Hospital Manipal. The study was carried out over a period of 2 years and included 136 women. After written informed consent, a detailed history and clinical examination was done. A detailed transvaginal sonography was done for each of the patients by a single observer on the Philips HD11XE machine two-dimensional transvaginal probe which included gel sonovaginography and real-time dynamic test called sliding sign. Chi-square test was used in this study. Sliding sign is highly specific, sensitive, and accurate for the detection of POD obliteration. It is 96.6% sensitive and 89.5% specific. It is 94.1% accurate and 94.5% positively predictive for the same. Transvaginal sonography is >92% specific for the detection of bowel and nonbowel DIE. The accuracy is over 91%. The negative predictability is 93.6% and 94.6%, respectively. Sliding sign is a useful, easy-to-perform, reproducible, and noninvasive modality for assessing the status of POD. Gel sonovaginography is also useful in accurately detecting the presence of deep infiltrating endometriotic deposits.


Role of cellular superoxide dismutase against reactive oxygen metabolite injury in cultured bovine aortic endothelial cells.
We examined the protective effect of cellular superoxide dismutase against extracellular hydrogen peroxide in cultured bovine aortic endothelial cells. 51Cr-labeled cells were exposed to hydrogen peroxide generated by glucose oxidase/glucose. Glucose oxidase caused a dose-dependent increase of 51Cr release. Pretreatment with diethyldithiocarbamate enhanced injury induced by glucose oxidase, corresponding with the degree of inhibition of endogenous superoxide dismutase activity. Inhibition of cellular superoxide dismutase by diethyldithiocarbamate was not associated either with alteration of other antioxidant defenses or with potentiation of nonoxidant injury. Enhanced glucose oxidase damage by diethyldithiocarbamate was prevented by chelating cellular iron. Inhibition of cellular xanthine oxidase neither prevented lysis by hydrogen peroxide nor diminished enhanced susceptibility by diethyldithiocarbamate. These results suggest that, in cultured endothelial cells: 1) cellular superoxide is involved in mediating hydrogen peroxide-induced damage; 2) superoxide, which would be generated upon exposure to excess hydrogen peroxide independently of cellular xanthine oxidase, promotes the Haber-Weiss reaction by initiating reduction of stored iron (Fe3+) to Fe2+; 3) cellular iron catalyzes the production of a more toxic species from these two oxygen metabolites; 4) cellular superoxide dismutase plays a critical role in preventing hydrogen peroxide damage by scavenging superoxide and consequently by inhibiting the generation of the toxic species.


Chiral diboranes as catalysts for the stereoselective organopolymerization of epoxides.
It is demonstrated that stereoselective polymerization of epoxides, long a domain of metal-based compounds, can also be achieved via the application of organocatalysts. A simple two-step synthesis starting from widely available 1,1'-bi-2-naphthol (BINOL) backbones yields diboranes which, in tandem with organobases, deliver isotactic-enriched (it) polyethers from the homopolymerization of racemic propylene oxide (PO) and other epoxides. Thereby, isotactic diad contents of up to 88% can be achieved, resulting in well-defined (1.1 < Đ M < 1.3) polyethers with high molar masses (M n > 100 000 g mol-1). Notably, it is also possible to grow it-enriched sequences of PPO on aliphatic polyester-type initiators, thus enabling the incorporation of stereocontrolled polyether blocks in more complex polymer architectures. It is expected that this ability will greatly benefit the preparation of polyether-containing additives. The BINOL-type diboranes can be readily modified, suggesting further potential as a platform from which optimized catalysts can be developed.


Functional and dynamic properties of visual peripersonal space.
In order to code visual peripersonal space, human and non-human primates need an integrated system that controls both visual and tactile inputs within peripersonal space around the face and the hand, based on visual experience of body parts. The existence of such a system in humans has been demonstrated, and there is evidence showing that visual peripersonal space relating to the hand has important dynamic properties, for example, it can be expanded and contracted depending on tool use. There is also evidence for a high degree of functional similarity between the characteristics of the visual peripersonal space in humans and in monkeys.


Continuous Dynamic Modeling of Regulated Cell Adhesion: Sorting, Intercalation, and Involution.
Cell-cell adhesion is essential for tissue growth and multicellular pattern formation and crucial for the cellular dynamics during embryogenesis and cancer progression. Understanding the dynamical gene regulation of cell adhesion molecules (CAMs) responsible for the emerging spatial tissue behaviors is a current challenge because of the complexity of these nonlinear interactions and feedback loops at different levels of abstraction-from genetic regulation to whole-organism shape formation. To extend our understanding of cell and tissue behaviors due to the regulation of adhesion molecules, here we present a novel, to our knowledge, model for the spatial dynamics of cellular patterning, growth, and shape formation due to the differential expression of CAMs and their regulation. Capturing the dynamic interplay between genetic regulation, CAM expression, and differential cell adhesion, the proposed continuous model can explain the complex and emergent spatial behaviors of cell populations that change their adhesion properties dynamically because of inter- and intracellular genetic regulation. This approach can demonstrate the mechanisms responsible for classical cell-sorting behaviors, cell intercalation in proliferating populations, and the involution of germ layer cells induced by a diffusing morphogen during gastrulation. The model makes predictions on the physical parameters controlling the amplitude and wavelength of a cellular intercalation interface, as well as the crucial role of N-cadherin regulation for the involution and migration of cells beyond the gradient of the morphogen Nodal during zebrafish gastrulation. Integrating the emergent spatial tissue behaviors with the regulation of genes responsible for essential cellular properties such as adhesion will pave the way toward understanding the genetic regulation of large-scale complex patterns and shapes formation in developmental, regenerative, and cancer biology.


Effects of 1,1,1-trichloroethane on enzymatic activity and bacterial community in anaerobic microcosm form sequencing batch reactors.
1,1,1-Trichloroethane (TCA), a major organic and groundwater contaminant, has very strong toxic effects on humans, plants and microorganisms. Effects of TCA on enzymatic activity and microbial diversity were investigated in the anaerobic sequencing batch reactor (ASBR) under methanogenic, nitrate-reducing, sulfate-reducing and benzene/toluene degrading conditions. The activities of three enzymes (lactate dehydrogenase, phosphatase and protease) were significantly decreased in the presence of 5 mg/L TCA. Within these three affected enzymes, phosphatase activity may serve as a noteworthy marker of bacterial toxicity. The activity of phosphatase was 0.2 U/L in methanogenic conditions with 5 mg/L TCA, which was 99% lower than the controls, and the enzyme activity was 18.6 U/L in methanogenic conditions with 1 mg/L TCA, which was 7% lower than the controls. DGGE profiles showed that TCA altered the bacterial community distribution and diversity obviously during the 21 day of TCA exposure. The enzyme activities decreased second lowest but TCA degrading strains Clostridium sp. DhR-2/LM-G01, Bacterial clone DCE25 and Bacterial clone DPHB06 were enriched in the methanogenic ASBR amended TCA.


Rhizobial and fungal symbioses show different requirements for calmodulin binding to calcium calmodulin-dependent protein kinase in Lotus japonicus.
Ca(2+)/calmodulin (CaM)-dependent protein kinase (CCaMK) is a key regulator of root nodule and arbuscular mycorrhizal symbioses and is believed to be a decoder for Ca(2+) signals induced by microbial symbionts. However, it is unclear how CCaMK is activated by these microbes. Here, we investigated in vivo activation of CCaMK in symbiotic signaling, focusing mainly on the significance of and epistatic relationships among functional domains of CCaMK. Loss-of-function mutations in EF-hand motifs revealed the critical importance of the third EF hand for CCaMK activation to promote infection of endosymbionts. However, a gain-of-function mutation (T265D) in the kinase domain compensated for these loss-of-function mutations in the EF hands. Mutation of the CaM binding domain abolished CaM binding and suppressed CCaMK(T265D) activity in rhizobial infection, but not in mycorrhization, indicating that the requirement for CaM binding to CCaMK differs between root nodule and arbuscular mycorrhizal symbioses. Homology modeling and mutagenesis studies showed that the hydrogen bond network including Thr265 has an important role in the regulation of CCaMK. Based on these genetic, biochemical, and structural studies, we propose an activation mechanism of CCaMK in which root nodule and arbuscular mycorrhizal symbioses are distinguished by differential regulation of CCaMK by CaM binding.


Cognitive distortions mediate depression and affective response to social acceptance and rejection.
The emotional context insensitivity (ECI) hypothesis suggests individuals with depression have blunted affective responses to both positive and negative events. We tested ECI in a social context to examine how depression relates to affective responses to social acceptance and rejection outcomes. Furthermore, we aimed to identify cognitive mechanisms linking depression with affective response to social feedback. Finally, we tested whether these processes are similar for social anxiety. 90 participants (age 18-26 years; 53 women) completed the two-visit Chatroom task. At Visit 1 they rated their expectations about being liked by 60 peers. At Visit 2 they completed self-reports of depressive and social anxiety symptoms, and of cognitive flexibility, then received acceptance or rejection feedback from each peer and rated their affective response. Greater depressive symptoms related to negative expectancy bias, lower cognitive flexibility, and less positive affective response to acceptance, but did not relate to rejection. Negative expectations and cognitive flexibility mediated the relationship between depressive symptoms and affective response for acceptance; only negative expectations mediated rejection responses. These cognitive mechanisms were not related to social anxiety. A community sample was used to assess depression. Rumination and current mood state were omitted as potential predictors of affective response. Findings support the ECI framework. Depression but not social anxiety interferes with positive and negative affect through cognitively mediated dampening of emotional response to social acceptance and rejection. Emotion regulation strategies in depression therapy can target social flexibility to improve alignment of affective reactions to social outcomes.


The linker histone Hho1 modulates the activity of ATP-dependent chromatin remodeling complexes.
Diverse factors play roles in chromatin dynamics, including linker proteins. Among them are high mobility group (HMG) box family proteins and linker histones. In the yeast Saccharomyces cerevisiae, Hmo1 has been identified as an HMG-box protein. This protein displays properties that are in agreement with this allocation. However, a number of studies have postulated that Hmo1 functions as a linker histone in yeast. On the other hand, when discovered, the Hho1 protein was identified as a linker histone. While multiple studies support this classification, some findings point to characteristics of Hho1 that are dissimilar to those commonly assigned to linker histones. In order to better understand the roles played by Hmo1 and Hho1 in chromatin dynamics and transcriptional regulation, we performed several analyses directly comparing these two proteins. Our analyses of genome-wide binding profiles support the belonging of Hmo1 to the HMGB family and Hho1 to the linker histones family. Interestingly, by performing protein-protein interaction analyses we found that both Hmo1 and Hho1 display physical interaction with the ATP-dependent chromatin remodeling complexes RSC, ISW1a and SWI/SNF. Moreover, by carrying out nucleosome remodeling assays, we found that both proteins stimulate the activity of the ISW1a complex. However, in the case of RSC, Hmo1 and Hho1 displayed differential properties, with Hho1 mainly showing an inhibitory effect. Our results are in agreement with the opposite roles played by RSC and ISW1a in chromatin dynamics and transcriptional regulation, and expand the view for the roles played by Hho1 and linker histones.


Bayesian Inference of Allelic Inclusion Rates in the Human T Cell Receptor Repertoire.
A small population of αβ T cells is characterized by the expression of more than one unique T cell receptor (TCR); this outcome is the result of "allelic inclusion," that is, inclusion of both α- or β-chain alleles during V(D)J recombination. Limitations in single-cell sequencing technology, however, have precluded comprehensive enumeration of these dual receptor T cells. Here, we develop and experimentally validate a fully Bayesian inference model capable of reliably estimating the true rate of α and β TCR allelic inclusion across two different emulsion-barcoding single-cell sequencing platforms. We provide a database composed of over 51,000 previously unpublished allelic inclusion TCR sequence sets drawn from eight healthy individuals and show that allelic inclusion contributes a distinct and functionally important set of sequences to the human TCR repertoire. This database and a Python implementation of our statistical inference model are freely available at our Github repository (https://github.com/JasonACarter/Allelic_inclusion).


Does omega-3 supplementation improve the inflammatory profile of patients with heart failure? a systematic review and meta-analysis.
Omega-3 fatty acids are potential anti-inflammatory agents that may exert beneficial outcomes in diseases characterised by increased inflammatory profile. The purpose of this study was to comprehensively evaluate the existing research on the effectiveness of n-3 fatty acid supplementation in lowering levels of circulating inflammatory cytokines in patients with heart failure (HF). From the beginning until October 2022, randomised controlled trials (RCTs) were the subject of PubMed, Scopus, Web of Science, and Cochrane Library literature search. Omega-3 fatty acid supplementation vs. placebo were compared in eligible RCTs to see how they affected patients with HF in terms of inflammation, primarily of tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and c-reactive protein (CRP). A meta-analysis employing the random effects inverse-variance model and standardised mean differences was performed to assess group differences. Ten studies were included in this systematic review and meta-analysis. Our main analysis (k = 5) revealed a beneficial response of n-3 fatty acid supplementation on serum TNF-a (SMD: - 1.13, 95% CI: - 1.75- - 0.50, I2 = 81%, P = 0.0004) and IL-6 levels (k = 4; SMD: - 1.27, 95% CI: - 1.88- - 0.66, I2 = 81%, P < 0.0001) compared to placebo; however, no changes were observed in relation to CRP (k = 6; SMD: - 0.14, 95% CI: - 0.35-0.07, I2 = 0%, P = 0.20). Omega-3 fatty acid supplementation may be a useful strategy for reducing inflammation in patients with HF, but given the paucity of current studies, future studies may increase the reliability of these findings.


Everolimus reduces BK polyomavirus infection by suppressing its replication and spread of infection.
BK polyomavirus-associated nephropathy is one of serious complications in transplant recipients. Everolimus-a mammalian target of rapamycin inhibitor-has been shown to reduce the incidence of BK polyomavirus infection in transplant recipients. In this study, the effects of everolimus were examined on viral replication and the spread of infection in BK polyomavirus-infected cultures. BK polyomavirus replicated in renal and pulmonary cells, contrary to that in hepatocytes, and spread as diffusely scattered patterns of infected cells, unlike plaque formation through the cell-to-cell mode. BK polyomavirus is stable to heat up to 65 °C with a particle per infectivity ratio of 5000, and the replication cycle was for approximately 34 h. Everolimus administration remarkably reduced the viral replication to 20% in cells treated with 0.1-10 ng/mL, the concentration at which everolimus reached the serum of transplant recipients. In addition, it reduced the amount of viral capsid protein 1 at 5 ng/mL without reducing the ratio of viral capsid protein 1 versus β-actin, and it also retained the pattern of viral capsid protein 1 localization in the nuclei. Everolimus suppressed the number of infected cells to 32.8% during a 14-day treatment, indicating the reduction of BK polyomavirus-infected cell mass to 18.8% of untreated cultures by modifying cellular functions. The reduction in the total number of BK polyomavirus infected cells by everolimus indicates that everolimus alleviates BK polyomavirus infection, including nephropathy in transplant recipients.


Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol.
Gender is considered as a pivotal determinant of mental health. Indeed, several psychiatric disorders such as anxiety and depression are more common and persistent in women than in men. In the past two decades, impaired brain energy metabolism has been highlighted as a risk factor for the development of these psychiatric disorders. However, comprehensive behavioural and neurobiological studies in brain regions relevant to anxiety and depression symptomatology are scarce. In the present study, we summarize findings describing cannabidiol effects on anxiety and depression in maternally separated female mice as a well-established rodent model of early-life stress associated with many mental disorders. Our results indicate that cannabidiol could prevent anxiolytic- and depressive-related behaviour in early-life stressed female mice. Additionally, maternal separation with early weaning (MSEW) caused long-term changes in brain oxidative metabolism in both nucleus accumbens and amygdalar complex measured by cytochrome c oxidase quantitative histochemistry. However, cannabidiol treatment could not revert brain oxidative metabolism impairment. Moreover, we identified hyperphosphorylation of mTOR and ERK 1/2 proteins in the amygdala but not in the striatum, that could also reflect altered brain intracellular signalling related with to bioenergetic impairment. Altogether, our study supports the hypothesis that MSEW induces profound long-lasting molecular changes in mTOR signalling and brain energy metabolism related to depressive-like and anxiety-like behaviours in female mice, which were partially ameliorated by CBD administration.


Effects of bilirubin on potassium (86Rb+) influx and ionic content in Ehrlich ascites cells.
Potassium influx, intracellular potassium and sodium content and cellular volume were determined in vitro in Ehrlich ascites cells in the presence of up to 0.8 mM bilirubin in the incubation medium. Bilirubin uptake into cells as a function of bilirubin concentration in the incubation medium increased linearly with a molar bilirubin/albumin ratio of 20 : 1. Potassium influx and intracellular content decreased while cellular volume increased after 180 min of incubation of cells in bilirubin at a molar bilirubin/albumin ratio of 20 : 1. At a bilirubin/albumin ratio 2 : 1, potassium influx decreased, cellular volume remained unchanged, and bilirubin uptake into cells became saturated at bilirubin concentrations greater than 0.3 mM. It is suggested that bilirubin-induced alterations in potassium gradients across cell membranes may play a role in toxic effects of bilirubin on cells.


Choroid plexus papilloma: light and electron microscopic study of three cases.
Three cases of choroid plexus papilloma were studied by light and electron microscopy. All had the typical papillary pattern, and, in addition, two exhibited solid areas of tumor growth which predominated in one case. PAS positive (diastase resistant) and argyrophilic cytoplasmic inclusions were present in all three tumors but were particularly abundant in the predominantly solid one. Ultrastructurally, the inclusions appeared as irregularly shaped structures containing lipid droplets, filamentous material and microtubules, and resembled the "silver bodies" of Biondi found in normal choroid plexus. Along with other ultrastructural features of normal choroid plexus, these cytoplasmic inclusions may be helpful in the differential diagnosis of papillary tumors involving the ventricular system.


Toxoplasma gondii: redistribution of monoclonal antibodies on tachyzoites during host cell invasion.
Immunodetection of protein P30, a major surface antigen of Toxoplasma gondii tachyzoites, by a specific monoclonal antibody has demonstrated a homogenous distribution of this antigen on the surface of intra- and extracellular tachyzoites at all stages of their endodyogenic development. On living zoites, no redistribution of anti-P30 was obtained, contrasting with the capping obtained with antiserum to T. gondii. Upon invasion of a host cell, however, most of the coat of anti-P30 was shed from preincubated zoites at the level of the moving junction governing the entry of the parasite into the host cell.


A simple, rapid method for the extraction of whole fire ant venom (Insecta: Formicidae: Solenopsis).
The invasive fire ant Solenopsis invicta is medically important because its venom is highly potent. However, almost nothing is known about fire ant venom proteins because obtaining even milligram-amounts of these proteins has been prohibitively challenging. We present a simple and fast method of obtaining whole venom compounds from large quantities of fire ants. For this, we separate the ants are from the nest soil, immerse them in dual-phase mixture of apolar organic solvent and water, and evaporate each solvent phase in separate. The remaining extract from the aqueous phase is largely made up of ant venom proteins. We confirmed this by using 2D gel electrophoresis while also demonstrating that our new approach yields the same proteins obtained by other authors using less efficient traditional methods.


A 12-month, randomized, controlled study to evaluate exposure and cardiovascular risk factors in adult smokers switching from conventional cigarettes to a second-generation electrically heated cigarette smoking system.
This randomized, controlled, forced-switching, open-label, parallel-group study in 97 adult male and female smokers of conventional cigarettes evaluated biomarkers of tobacco smoke exposure and cardiovascular risk factors. After baseline measurements, smokers were either switched to a second-generation electrically heated cigarette smoking system (EHCSS) or continued smoking conventional cigarettes for 12 months. Biomarkers of exposure and cardiovascular risk factors were measured at 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 months. There was a rapid and sustained reduction in all biomarkers of exposure after switching to the EHCSS, with statistically significant reductions from baseline in nicotine equivalents (-18%), plasma cotinine (-16%), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (-73%), total 1-hydroxypyrene (-53%), urine mutagenicity (-52%), 4-aminobiphenyl hemoglobin adducts (-43%), carboxyhemoglobin AUC7-23 h (-80%), and 3-hydroxypropylmercapturic acid (-35%). These reductions in exposure in the EHCSS group were associated with statistically significant and pathophysiologically favorable changes in several cardiovascular risk factors, including white blood cell count (-0.78 x 10(3)/microL), hemoglobin (-0.16 g/dL), hematocrit (-0.44%), urine 11-dehydrothromboxane B2 (-374 ng/24 h), and high-density lipoprotein cholesterol (+5 mg/dL).


A gene harvest revealing the archeology and complexity of human disease.
An inflection point in genetics has been reached and was witnessed at the Genomics of Common Diseases meeting (http://www.nature.com/ng/meetings/genomics) co-sponsored by the Wellcome Trust, held at the Wellcome Trust Hinxton Conference Centre July 7-10, 2007 and co-organized by Tim Aitman, David Altshuler and Eddy Rubin.


Ethylene, ACC, and the Plant Growth-Promoting Enzyme ACC Deaminase.
Here, a brief summary of the biosynthesis of 1-aminocyclopropane-1-carboxylate (ACC) and ethylene in plants, as well as overviews of how ACC and ethylene act as signaling molecules in plants, is presented. Next, how the bacterial enzyme ACC deaminase cleaves plant-produced ACC and thereby decreases or prevents the ethylene or ACC modulation of plant gene expression is considered. A detailed model of ACC deaminase functioning, including the role of indoleacetic acid (IAA), is presented. Given that ACC is a signaling molecule under some circumstances, this suggests that ACC, which appears to have evolved prior to ethylene, may have been a major signaling molecule in primitive plants prior to the evolution of ethylene and ethylene signaling. Due to their involvement in stimulating ethylene production, the role of D-amino acids in plants is then considered. The enzyme D-cysteine desulfhydrase, which is structurally very similar to ACC deaminase, is briefly discussed and the possibility that ACC deaminase arose as a variant of D-cysteine desulfhydrase is suggested.


Rit signaling contributes to interferon-gamma-induced dendritic retraction via p38 mitogen-activated protein kinase activation.
The proinflammatory cytokine interferon-gamma (IFNgamma) alters neuronal connectivity via selective regressive effects on dendrites but the signaling pathways that mediate this effect are poorly understood. We recently demonstrated that signaling by Rit, a member of the Ras family of GTPases, modulates dendritic growth in primary cultures of sympathetic and hippocampal neurons. In this study, we investigated a role for Rit signaling in IFNgamma-induced dendritic retraction. Expression of a dominant negative Rit mutant inhibited IFNgamma-induced dendritic retraction in cultured embryonic rat sympathetic and hippocampal neurons. In pheochromacytoma cells and hippocampal neurons, IFNgamma caused rapid Rit activation as indicated by increased GTP binding to Rit. Silencing of Rit by RNA interference suppressed IFNgamma-elicited activation of p38 MAPK in pheochromacytoma cells, and pharmacological inhibition of p38 MAPK significantly attenuated the dendrite-inhibiting effects of IFNgamma in cultured sympathetic and hippocampal neurons without altering signal transducer and activator of transcription 1 activation. These observations identify Rit as a downstream target of IFNgamma and suggest that a novel IFNgamma-Rit-p38 signaling pathway contributes to dendritic retraction and may, therefore, represent a potential therapeutic target in diseases with a significant neuroinflammatory component.


Divisional role of quantitative HER2 testing in breast cancer.
Human epidermal growth factor receptor 2 (HER2) is amplified in human breast cancers in which therapy targeted to HER2 significantly improves patient outcome. We re-visited the use of real-time quantitative polymerase chain reaction (qPCR)-based assays using formalin-fixed paraffin-embedded (FFPE) tissues as alternative methods and investigated their particular clinical relevance. DNA and RNA were isolated from FFPE specimens and HER2 status was assessed by qPCR in 249 consecutive patients with primary breast cancer. Concordance with results forg immunohistochemistry (IHC) and in situ hybridization (ISH), clinical characteristics and survival was assessed. HER2 gene copy number had a stronger correlation with clinicopathological characteristics and excellent concordance with IHC/ISH results (Sensitivity: 96.7 %; concordance: 99.2 %). HER2 gene expression showed inadequate sensitivity, rendering it unsuitable to determine HER2 status (Sensitivity: 46.7 %; concordance: 92.1 %), but lower HER2 gene expression, leading to the classification of many cases as "false negative", contributed to a prediction of better prognosis within the HER2-amplified subpopulation. Quantitative HER2 assessments are suggested to have evolved their accuracy in this decade, which can be a potential alternative for HER2 diagnosis in line with the in situ method, while HER2 gene expression levels could provide additional information regarding prognosis or therapeutic strategy within a HER2-amplified subpopulation.


Role of radiotherapy in the management of rare solid thoracic tumors of the adults.
Thoracic tumors include more than one hundred histopathological subtypes. Rare thoracic malignancies can be defined as representing less than 1% of all thoracic tumors. The European Rare Cancer Surveillance Project (RARECARE) identified rarity as an incidence less than 6 for 100,000 people, with significant difference of prevalence between them. Modalities of treatment for these pathologies include surgery, radiotherapy, and systemic therapies. In this article, we aim to discuss role and techniques of radiotherapy in management of rare solid thoracic tumors in adults, focusing on different anatomical locations such as lung parenchyma, mediastinum, vessels, chest wall and pleural cavity.


Fetal lamb lung lavage and its effect on lung phosphatidylcholine.
The lungs of intrauterine 135--136-day-old lambs were lavaged with amnionic fluid, with or without meconium, to determine the effect on lung phosphatidylcholine (PC) concentration, synthesis, and function. No differences were apparent between animals lavaged with amnionic fluid or amnionic fluid with meconium. When lavaged lungs were compared to nonlavaged controls, no detectable differences were observed in histology or the quantity of saturated (SPC) and unsaturated phosphatidylcholine (UPC). However, the lavaged lungs retained a larger fraction of maximal lung volume at 5 cm H2O distending pressure and the incorporation of (32P) orthophosphate into lung PC was significantly reduced. In addition, two lavaged animals who became acidotic (pH less than 7.20) exhibited decreased incorporation of 14C) palmitate into whole lung unsaturated, and saturated phosphatidylcholine. These data indicate that amnionic fluid can reduce lamb lung de novo synthesis of PC and may contribute to the alterations in lung PC found in neonatal syndromes of respiratory distress. Acidosis may accentuate this effect.


Revealing the functionality of hypothetical protein KPN00728 from Klebsiella pneumoniae MGH78578: molecular dynamics simulation approaches.
Previously, the hypothetical protein, KPN00728 from Klebsiella pneumoniae MGH78578 was the Succinate dehydrogenase (SDH) chain C subunit via structural prediction and molecular docking simulation studies. However, due to limitation in docking simulation, an in-depth understanding of how SDH interaction occurs across the transmembrane of mitochondria could not be provided. In this present study, molecular dynamics (MD) simulation of KPN00728 and SDH chain D in a membrane was performed in order to gain a deeper insight into its molecular role as SDH. Structural stability was successfully obtained in the calculation for area per lipid, tail order parameter, thickness of lipid and secondary structural properties. Interestingly, water molecules were found to be highly possible in mediating the interaction between Ubiquinone (UQ) and SDH chain C via interaction with Ser27 and Arg31 residues as compared with earlier docking study. Polar residues such as Asp95 and Glu101 (KPN00728), Asp15 and Glu78 (SDH chain D) might have contributed in the creation of a polar environment which is essential for electron transport chain in Krebs cycle. As a conclusion, a part from the structural stability comparability, the dynamic of the interacting residues and hydrogen bonding analysis had further proved that the interaction of KPN00728 as SDH is preserved and well agreed with our postulation earlier.


Improvement of Refractory Ulcerative Proctitis With Sacral Nerve Stimulation.
Sacral nerve stimulation (SNS) is recognized for its efficiency and safety for anal incontinence, preventing high morbidity. Evidence from the literature suggests extending SNS to diseases associated with problems of intestinal barrier permeability. The aim of this study was to highlight clinical evidence of the beneficial impact of SNS in a refractory proctitis case report. A permanent SNS was performed successfully in a patient with proctitis after implantation of the neuromodulator. Despite immunosuppressive drugs, the patient was experiencing mucus and blood discharge, pain, and fecal incontinence. To relieve fecal incontinence, SNS was tested without modification of medications. Disease activity, endoscopic and histologic score, ex vivo barrier permeability, expression of inflammatory cytokines (transforming growth factor-β, tumor necrosis factor α, Interleukin-6, Interleukin-8), and junctional proteins (ZO-1, claudin-1, occludin) were assessed before and after SNS to observe the impact of SNS other than for incontinence. After a 3-week period of temporary stimulation, the patient experienced significant improvement with a decrease in fecal incontinence and disease activity scores. Both endoscopic and histologic scores showed improvement. The rectal barrier permeability decreased with SNS, whereas junctional protein mRNA expression transiently increased. Clinical and histologic improvement was sustained over time. After 18 months of permanent stimulation, the patient remained improved by SNS. This work demonstrates the relevance to explore further indications of SNS beyond fecal incontinence.


Case report 809: Squamous cell carcinoma of the skin invading the shoulder.
Bone invasion by squamous cell carcinoma (SCC) is very rare in locations other than the head and neck region. The case of a 30-year-old man with slow-growing SCC of the shoulder region, aggressively invading neighboring bony structures, was presented.


Allergic skin inflammation and S. aureus skin colonization are mutually reinforcing.
Atopic dermatitis (AD) lesional skin is often colonized with S. aureus, and the load of S. aureus correlates with disease severity. However, a causative and mechanistic link between S. aureus skin colonization and severity of AD is not well established. We made use of well-established mouse model of AD elicited by epicutaneous sensitization of tape stripped skin with ovalbumin to investigate the relationship between allergic skin inflammation and cutaneous S. aureus colonization. Topical application of S aureus exacerbated allergic skin inflammation induced by epicutaneous sensitization with ovalbumin, whereas allergic skin inflammation generated a permissive environment for S. aureus persistence. Our results establish a mutually reinforcing role of allergic skin inflammation and S. aureus skin colonization.


Spiking of performance reference compounds in low density polyethylene and silicone passive water samplers.
A method for spiking performance reference compounds (PRCs) into low density polyethylene (LDPE) and silicone polymers is described. This method is based on equilibration of the polymers in aqueous/methanolic solutions of PRCs. Equilibration times range from minutes to hours for perdeuterated polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) with a hydrophobicity in the range 3.9 < logKow < 7.7. Best results were obtained for methanol-water ratios of 80/20 (v/v). The method allows for the use of PRCs for in situ calibration of the uptake kinetics of these solvent-free sampling phases in a similar way as for semipermeable membrane devices (SPMDs).


In vivo and in vitro binding of 1,2-dibromoethane and 1,2-dichloroethane to macromolecules in rat and mouse organs.
The comparative interaction of equimolar amounts of 1,2-dichloroethane and 1,2-dibromoethane with rat and mouse nucleic acids was studied in both in vivo (liver, lung, kidney and stomach) and in vitro (liver microsomal and/or cytosolic fractions) systems. In vivo, liver and kidney DNA showed the highest labeling, whereas the binding to lung DNA was barely detectable. Dibromoethane was more highly reactive than dichloroethane in both species. With dichloroethane, mouse DNA labeling was higher than rat DNA labeling whatever the organ considered: the opposite was seen for the bioactivation of dibromoethane. RNA and protein labelings were higher than DNA labeling, with no particular pattern in terms of organ or species involvement. In vitro, in addition to a low chemical reactivity towards nucleic acids shown by haloethanes per se, both compounds were bioactivated by either liver microsomes and cytosolic fractions to reactive forms capable of binding to DNA and polynucleotides. UV irradiation did not photoactivate dibromoethane and dichloroethane. The in vitro interaction with DNA mediated by enzymatic fractions was PB-inducible (one order of magnitude, using rat microsomes). In vitro bioactivation of haloethanes was mainly performed by microsomes in the case of dichloroethane and by cytosolic fractions in the case of dibromoethane. When microsomes plus cytosol were used, rat enzymes were more efficient than mouse enzymes in inducing a dibromoethane-DNA interaction: the opposite situation occurred for dichloroethane-DNA interaction, and this is in agreement with the in vivo pattern. In the presence of both metabolic pathways, addition or synergism occurred. Dibromoethane was always more reactive than dichloroethane. An indication of the presence of a microsomal GSH transferase was achieved for the activation of dibromoethane. No preferential binding in vitro to a specific polynucleotide was found. Polynucleotide labeling was higher than (or equal to) DNA binding. The labeling of microsomal RNA and proteins and of cytosolic proteins was many times lower than that of DNA or polynucleotides. The in vivo and in vitro data reported above give an unequivocal indication of the relative reactivity of the haloethanes examined with liver macromolecules from the two species and agree, on the whole, with the relative genotoxicity (DNA repair induction ability, mutagenicity and carcinogenicity) of the chemicals.


Tumor long-axis diameter and SUVmax predict long-term responders in 90Y-ibritumomab tiuxetan monotherapy.
90Y-ibritumomab tiuxetan (90Y-IT) is widely used, but the factors responsible for its optimal treatment effects are unknown. We enrolled 34 patients with relapsed indolent lymphoma treated with 90Y-IT monotherapy at Gunma University Hospital between 2003 and 2014 in the present study. Clinical data including computed tomography and 18-Fluoro-deoxyglucose positron emission tomography were retrospectively analyzed. The overall response rate and complete response rate were 91% and 82%, respectively. The median progression-free survival (PFS) and overall survival were 32 months and not reached, respectively. In univariate analysis, tumor long-axis diameter ≤ 2.5 cm, maximum standardized uptake value (SUVmax) ≤ 6.5, localized disease, normal levels of serum soluble interleukin-2 receptor, and the number of involved nodal sites ≤ 3 immediately prior to 90Y-IT were associated with median PFS greater than 6 years. However, in multivariate analysis, only tumor long-axis diameter ≤ 2.5 cm and SUVmax ≤ 6.5 affected PFS [hazard ratio (HR) 0.130, P = 0.0021 and HR 0.283, P = 0.0311, respectively]. Patients with only one prior regimen needed less granulocyte colony-stimulating factor and platelet transfusion. Thus, 90Y-IT treatment should be considered for patients with indolent lymphoma in first relapse who have tumor long-axis diameter ≤ 2.5 cm and SUVmax ≤ 6.5.


Clinical relevance of flow cytometric immunophenotyping of the cerebrospinal fluid in patients with diffuse large B-cell lymphoma.
Central nervous system (CNS) relapse is an uncommon but dramatic complication of diffuse large B-cell lymphoma (DLBCL). Several studies have demonstrated the superiority of cerebrospinal fluid (CSF) flow cytometry (FCM), as compared with conventional cytology (CC), in detecting occult leptomeningeal disease. The clinical relevance of a positive FCM still has to be clarified. We analyzed CSF from 114 DLBCL patients at diagnosis (n = 95) or at relapse (n = 19) by FCM and CC. Most patients received meningeal prophylaxis. FCM results did not influence treatment strategies. Fourteen samples were FCM+, versus one CC+ (also FCM+). Within all patients without neurological symptoms (n = 101), four (4%) relapsed in the CNS, with a median time to relapse of 5.2 months. Only one-fourth (25%) was FCM+ before relapse. More than one extranodal disease site and elevated lactate dehydrogenase levels were associated with an increased risk of CNS relapse. FCM gives far more positive results than CC. However, a positive FCM result did not translate into a significant increase in CNS relapse rate in this histologically uniform population receiving CNS prophylaxis.


Implementing seclusion in forensic mental health care: A qualitative study of staff decision making.
Forensic mental health nursing is a complex role and there is a tension between maintaining safety and promoting a therapeutic and patient centred approach. The use of restrictive practises such as seclusion is an issue. Two focus groups with registered nurses exploring attitudes and factors used in decision-making about seclusion use were analysed using interpretive description. Participants described the need to reduce the use of seclusion and the problematic nature of its utility as an ongoing intervention in contemporary mental healthcare. It was clear that there were complexities and competing variables involved in the decision-making process.


Confocal microscopy immunofluorescence localization of desmin and other intermediate filament proteins in fetal rat livers.
Immunolocalization of desmin in fetal rat livers shows that on day 12 of gestation a high number of liver cells express desmin. This number decreases from day 14 onward. On day 20 about the same density of desmin-containing cells is found in fetal rat livers as is found in adult rat livers. Desmin-containing cells show two types of labeling patterns, especially on days 12 and 13 of gestation: (a) a basketlike network of intermediate filaments throughout the whole cell, similar to the labeling pattern of cytokeratin in hepatocytes; and (b) more strongly labeled intermediate filaments developing long and slender processes between adjacent cells, close to the labeling pattern of Ito cells in adult rats. From day 14 of gestation, the first type becomes rare, and from day 18 only the second type remains. Double-labeling experiments show that coexpression of desmin and cytokeratin is found in cells of the first type on days 12, 13 and 14 of gestation. Cells containing desmin with the labeling pattern of the second type never express cytokeratin. Coexpression of vimentin and cytokeratin is never found in fetal hepatocytes, even on day 12 of gestation. Numerous nonhepatocyte cells coexpress desmin and vimentin, but some cells contain vimentin or desmin alone. In desmin-containing cells the labeling pattern is of the first type (basketlike network). These results suggest that in early stages of fetal liver development, desmin is found in two different types of liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulatory T cell therapy: Current and future design perspectives.
Regulatory T cells (Tregs) maintain immune equilibrium by suppressing immune responses through various multistep contact dependent and independent mechanisms. Cellular therapy using polyclonal Tregs in transplantation and autoimmune diseases has shown promise in preclinical models and clinical trials. Although novel approaches have been developed to improve specificity and efficacy of antigen specific Treg based therapies, widespread application is currently restricted. To date, design-based approaches to improve the potency and persistence of engineered chimeric antigen receptor (CAR) Tregs are limited. Here, we describe currently available Treg based therapies, their advantages and limitations for implementation in clinical studies. We also examine various strategies for improving CAR T cell design that can potentially be applied to CAR Tregs, such as identifying co-stimulatory signalling domains that enhance suppressive ability, determining optimal scFv affinity/avidity, and co-expression of accessory molecules. Finally, we discuss the importance of tailoring CAR Treg design to suit the individual disease.


Lactate monooxygenase. II. Site-directed mutagenesis of the postulated active site base histidine 290.
Lactate monooxygenase catalyzes the oxidation of L-lactate with molecular oxygen to acetate, CO2, and water. Histidine 290 has been proposed to be the active site base in lactate monooxygenase (Giegel, D. A., Williams, C. H., Jr., and Massey, V. (1990) J. Biol. Chem. 265, 6626-6632) and was mutated to a glutamine (H290Q). The mutant enzyme shows properties that support strongly the postulated function of the histidine. The ability of L-lactate to reduce the enzyme flavin is essentially abolished, whereas reoxidation of reduced enzyme with oxygen proceeds at 1.4 x 10(4) M-1 s-1, a rate essentially like that found in the wild type enzyme. The substrate, L-lactate, is bound with a Kd equal to 2.0 x 10(-2) M, and D-lactate, a competitive inhibitor with a Kd of 3.1 x 10(-3) M. Both values are similar to binding measured in the wild type enzyme. Unlike the situation with wild type enzyme, where the transition state analog oxalate is bound tightly in a two-step reaction involving proton uptake from solution (Ghisla, S., and Massey, V. (1977) J. Biol. Chem. 252, 6729-6735), the mutant enzyme binds oxalate weakly, in a single step reaction, with a Kd in the order of 0.1 M. No effect was observed upon varying the pH, indicating that binding does not include a protonation step. Replacing the histidine also has a significant effect on the ability of the enzyme to stabilize the flavin N(5)-sulfite adduct. Sulfite is bound at least 1000-fold weaker than it is in the wild type enzyme.


The Electron Transfer Process in Mixed Valence Compounds with a Low-lying Energy Bridge in Different Oxidation States.
Mixed-valence compounds with the iso-cyanidometal-ligand bridge in different oxidation states are used as models for the investigation of the electron-transfer process. We synthesized a series of trimetallic isocyanidometal-bridged compounds with [Fe-CN-Ru-NC-Fe]n+ (n=2-4), in which the one-electron oxidation product (N3+ ) and two-electron oxidation product (N4+ ) compounds possess an isocyanidometal bridge whose energy is, respectively lower and slightly higher than the terminal metal centers energies. For the N3+ compounds, the bridge state (FeII -RuIII -FeII ) and mixed-valence states (FeIII -RuII -FeII or FeII -RuII -FeIII ) could be simultaneously observed on the IR timescale. For the N4+ compounds, as the donor becomes stronger the electron transfer bridge excited state (FeIII -RuII -FeIII ) becomes more and more stable, and even becomes ground state due to the strong electronic coupling between Fe and Ru.


Cerebral white matter lesions and silent cerebral infarcts in postmenopausal women with polycystic ovary syndrome.
The association between polycystic ovary syndrome (PCOS) and cardiovascular disease remains unclear. Our objective was to examine the relation of PCOS with cerebrovascular disease measured by brain magnetic resonance imaging (MRI) as white matter lesions (WMLs) and silent cerebral infarcts (SCIs). Seventy postmenopausal women with PCOS and 140 controls participated in the case-control, cross-sectional study. Clinical, anthropometric, hormonal and metabolic parameters were measured. WMLs and SCIs were evaluated by brain MRI. Compared with controls, postmenopausal women with PCOS had higher mean body mass index, larger waist hip ratio, higher level of low-density lipoprotein cholesterol, free androgen index and lower sex hormone-binding globulin level. The PCOS group had a significantly higher prevalence of WMLs (40% versus 22%, p = 0.009), and SCIs (17% versus 7%, p = 0.032) compared to the control group. Postmenopausal women with PCOS are associated with WMLs and SCIs.


Calprotectin and cross-linked N-telopeptides of type I collagen levels in crevicular fluid from implant sites with peri-implant diseases: a pilot study.
Peri-implant crevicular fluid (PICF) contains calprotectin and NTx, which are markers for inflammation and bone resorption, respectively. The aims of this pilot study were to compare calprotectin and NTx levels in PICF from implant sites with or without peri-implant diseases and to evaluate the usefulness of calprotectin and NTx as diagnostic markers for peri-implant diseases. Thirty-five patients with dental implants participated in this pilot study. PICF samples were collected from peri-implant disease sites (n = 40) and non-diseased (healthy) sites (n = 34) after clinical indicators including probing depth (PD), bleeding on probing (BOP), gingival index (GI), and bone loss (BL) rate were investigated. Calprotectin and NTx amounts in PICF were measured using their respective ELISA kits and then compared between diseased and healthy samples. The relationship between PICF calprotectin or NTx levels and clinical indicator levels was investigated. A receiver operating characteristic (ROC) curve analysis of calprotectin and NTx was performed to predict peri-implant diseases. Calprotectin and NTx levels in PICF were significantly higher from peri-implant disease sites than from healthy sites. PICF calprotectin amounts correlated with PD, and its levels were significantly higher in the GI-1 and GI-2 groups than in the GI-0 group. PICF NTx amounts correlated with PD and the BL rate. ROC curves indicated that PICF calprotectin and NTx are useful biomarkers for peri-implant diseases. Calprotectin and NTx in PICF have potential as biomarkers for the diagnosis of peri-implant diseases.


Intranasal fentanyl provides adequate postoperative analgesia in pediatric patients.
To evaluate intranasally administered fentanyl for postoperative analgesia in pediatric patients. Thirty-two children aged four to eight years, ASA physical status I and II were included in this prospective randomized controlled study. In the postoperative care unit, patients were allocated to receive fentanyl, using a double-blind study design, either intranasally (Group I) or intravenously (Group II) in small titrated doses until they became pain free or side effects appeared which prohibited continuation of the drug. Satisfactory analgesia was achieved in both groups, though the required drug dosage was higher in the intranasal group (1.43 +/- 0.39 microg.kg(-1)). Onset of analgesia tended to be slower via the intranasal route compared to the iv route (13 +/- 4.5 vs 8.3 +/- 3.08 min; P=not significant). Side effects observed in this series were within an acceptable range and similar for both modalities. The intranasal route provides a good alternative for administration of fentanyl in pediatric surgical patients.


Polyps of the urethra in children.
The authors present two cases of polyps of the urethra occurring exclusively in boys: one in a 12-month-old infant, the other in a 15-year-old boy. In both patients the polyp caused dysuria or urinary retention. Diagnosis was based on mictional cystography. This examination usually gives a picture of a filling defect spotted in the area of the bladder neck. During miction the defect may move deeper into the urethra. An endoscopic examination may be also helpful. The authors believe that treatment should consist in total excision of the polyp together with its base through the open urinary bladder. Polyps of the urethra have to be differentiated from a valve of the posterior urethra or a shadowless calculus. After total excision of the polyp prognosis is good.


The role of social work in a veterinary hospital setting.
Social workers can assist veterinarians and their clients in dealing with such difficult situations as euthanasia decisions, grief reactions, and professional stress. They are already at work at The Animal Medical Center, where they counsel clients individually and in groups, consult with veterinarians on client relations and how to cope with their own stress, and develop educational programs for employees and others.


Effect of hormones on primary cell cultures from pregnancy-dependent mouse mammary tumors.
No hormone combination was successful in maintaining long term primary cultures of pregnancy-dependent mammary tumors. Insulin provided the most consistent dose dependent stimulatory effect on short term proliferation as measured by 3H-TdR incorporation into DNA. Insulin in combination with corticosterone and prolactin produced the greatest stimulatory effect in most tumors. Both insulin at 5 microgram/ml and insulin, prolactin and hydrocortisone induced a partially synchronous wave of DNA synthesis in restimulated cultures. The time course of the wave of DNA synthesis was different for different hormone treatments. Insulin as 5 microgram/ml caused an earlier wave of DNA synthesis than insulin, prolactin plus corticosterone.


The causal relationship between circulating biomarkersand the risk of bipolar disorder: A two-sample Mendelian randomization study.
To identify susceptible biomarkers for the development of bipolar disorder (BD), we conducted a Mendelian Randomization (MR) design to screen circulating proteins for the potential risk of bipolar disorder systematically. We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of 4782 human circulating proteins on the risk of bipolar disorder. 376 circulating biomarkers were selected in MR estimation (4406 circulating proteins with less than 3 SNPs were excluded) with 5368 European descents. GWAS meta-analysis of the potential role of all-cause bipolar disorder arose from the Psychiatric Genomics Consortium (41,917 cases, 371,549 controls). After IVW and sensitivity analysis, 4 circulating proteins having causal effects on bipolar disorder were identified. ISG15, as a key player in the innate immune response, decreased the risk of bipolar disorder causally (OR = 0.92, 95% CI = 0.89-0.94, P = 1.46e-09). Furthermore, MLN decreased the risk of bipolar disorder causally (OR = 0.94, 95% CI = 0.91-0.97, P = 1.04e-04). In addition, SFTPC (OR = 0.91, 95% CI = 0.86-0.96, P = 4.47e-04) and VCY (OR = 0.86, 95% CI = 0.77-0.96, P = 8.55e-03) presented a suggestive association with bipolar disorder. Our findings indicated that ISG15 and MLN showed evidence of causality in bipolar disorder and provided a promising target for the diagnosis and treatment of diseases.


Future expectations for critical care nurses. Competence in immunotherapy.
Immunotherapy is a promising therapy for the treatment of some forms of cancer. This research therapy uses normal immune system substances such as IL-2 to stimulate the immune system to kill tumor cells while sparing normal tissues. Many side effects of IL-2 have been identified. The most serious of these effects involves the cardiovascular, renal, and pulmonary systems. Patients who experience these IL-2-related toxicities are effectively managed in the intensive care unit. The critical care nurse has a major role in the monitoring and management of this patient population. Hospitals that participate in this research treatment for cancer are increasing. In the near future, competence in immunotherapy will be an expectation for many critical care nurses.


Genetic Characterization of a Listeria monocytogenes Serotype IVb Variant 1 Strain Isolated from Vegetal Matrix in Italy.
We report the chromosome and plasmid sequences of a strain of Listeria monocytogenes IVb variant 1, a recently emerging serotype, isolated in Italy from ready-to-eat vegetables.


Molecular and morphological phylogenetic analysis of Brachiaria and Urochloa (Poaceae).
The taxonomic relationships of Brachiaria and Urochloa have been questioned based on previous morphological studies. In this paper, we reconsider the phylogenetic relationships of these genera using 22 species of Brachiaria and Urochloa and six species of Paniceae as out-groups. The ITS1, 5.8S, and ITS2 region (internal transcribed spacer) of nuclear ribosomal DNA and eight morphological characters of the inflorescence were compiled into a data matrix. The cladistic analyses suggest that Urochloa-Brachiaria as a complex is paraphyletic with Eriochloa and Melinis. Species of all these genera share molecular synapomorphies and belong to the same monophyletic groups. The results confirm the continuous gradation between those genera previously found in several morphological studies. Therefore, the following eight new combinations are made: Urochloa bovonei (Chiov.) A.M. Torres & C.M. Morton, Urochloa dura (Stapf) A.M. Torres & C.M. Morton, Urochloa dura var. dura (Stapf) A.M. Torres & C.M. Morton, Urochloa dura var. pilosa (J.G. Anderson) A.M. Torres & C.M. Morton, Urochloa lachnantha (Hochst.) A.M. Torres & C.M. Morton, Urochloa leersioides (Hochst.) A.M. Torres & C.M. Morton, Urochloa nigropedata (Munro ex Ficalho & Hiern) A.M. Torres & C.M. Morton, and Urochloa subulifolia (Mez) A.M. Torres & C.M. Morton.


Assessing the benefits and usefulness of Schwartz Centre rounds in second-year medical students using clinical educator-facilitated group work session: not just "a facilitated moan"!
An experiential curriculum exposing medical students to the clinic early has many benefits but comes with the emotional stress this environment engenders. Schwartz rounds (SR) are an effective means to combat emotional stress and increasingly used in UK and USA hospitals. Recent studies show that the SR format may also provide benefits for medical students. This study aimed to investigate whether the guidance of SR in second year medical students provides the same benefits as to healthcare professionals. SR assessment involved 83 s year MBChB students in facilitated groupwork sessions. Topics discussed were "change and resilience" and "duty of candour". Students completed a Likert Scale questionnaire evaluating outcomes proffered by the Point of Care Foundation in collaboration with the Schwartz Foundation, with freeform feedback. There was an 86% completion rate with 25% providing written feedback. Participants were more likely to agree than disagree that SR were beneficial. SR effectiveness in enhancing students' working relationship awareness and skills was strongly correlated with understanding the purpose of, and engagement with, the SR (P < 0.001). Similarly, engagement with the SR was strongly correlated with self-reporting of enhanced patient-centredness (P < 0.001). Freeform feedback could be grouped into five themes that revolved around understanding of the SR and engagement with the process. Many positive comments regarded the SR as a forum not only to "learn experientially" but to so in a "safe environment". Many negative comments stemmed from students not seeing any benefits of engagement with the SR, in that sharing experiences was "unbeneficial", "empathy is inherent and not learnt", or that sharing emotional problems is simply "moaning". SRs are an effective way of fostering empathy and understanding towards patients and colleagues. However, for the students to benefit fully from the SR it is necessary for them to engage and understand the process. Therefore, for the successful implementation of SR into pre-clinical medical education, it is important to help students realise that SR are not merely a "facilitated whinge".


The reverse mortgage: a tool for funding long-term care and increasing public housing supply in Spain.
Population ageing is one of the most significant challenges facing the world in the twenty-first century. Furthermore, people aged over 65 typically have a level of income below the national average, but the homeownership rate among those in this age group tends to be high. Equity release schemes, specifically reverse mortgages, can help cover increased care costs and ensure a reasonable level of income, thus guaranteeing the well-being of older adults. However, this product has not been greatly developed by private entities. If the State were to implement this financial operation through public administrations, it could obtain homes that might then be included in public housing stocks. Thus, our paper aims to contribute to the literature on government-based reverse mortgage systems. Under our assumptions, the results showed that if 313,833 homes were reverse-mortgaged, the investment by the public administration would be around 0.73% GDP, with this being a feasible proposal. This work helps to create alternative methods to finance problems related with the ageing of societies from a public perspective.


The varicella-zoster virus-mediated delayed host shutoff: open reading frame 17 has no major function, whereas immediate-early 63 protein represses heterologous gene expression.
We reported that varicella-zoster virus (VZV) causes a delayed host shutoff during its replicative cycle. VZV open reading frame 17 (ORF17) is the homologue of the herpes simplex virus (HSV) UL41 gene encoding the virion host shutoff (vhs) protein which is responsible for the shutoff effect observed in HSV-infected cells. In the present study, we demonstrated that ORF17 is expressed as a late protein during the VZV replicative cycle in different infected permissive cell lines which showed a delayed shutoff of cellular RNA. A cell line with stable expression of VZV ORF17 was infected with VZV. In these cells, VZV replication and delayed host shutoff remained unchanged when compared to normal infected cells. ORF17 was not capable of repressing the expression of the beta-gal reporter gene under the control of the human cytomegalovirus immediate-early gene promoter or to inhibit the expression of a CAT reporter gene under the control of the human GAPDH promoter, indicating that ORF17 has no major function in the VZV-mediated delayed host shutoff. To determine whether other viral factors are involved in the host shutoff, a series of cotransfection assays was performed. We found that the immediate-early 63 protein (IE63) was able to downregulate the expression of reporter genes under the control of the two heterologous promoters, indicating that this viral factor can be involved in the VZV-mediated delayed host shutoff. Other factors can be also implicated to modulate the repressing action of IE63 to achieve a precise balance between the viral and cellular gene expression.


Heating of metallic implants and instruments induced by gradient switching in a 1.5-Tesla whole-body unit.
To examine gradient switching-induced heating of metallic parts. Copper and titanium frames and sheets ( approximately 50 x 50 mm(2), 1.5 mm thick, frame width = 3 mm) surrounded by air were positioned in the scanner perpendicular to the static field horizontally 20 cm off-center. During the execution of a sequence (three-dimensional [3D] true fast imaging with steady precession [True-FISP], TR = 6.4 msec) exploiting the gradient capabilities (maximum gradient = 40 mT/m, maximum slew rate = 200 T/m/second), heating was measured with an infrared camera. Radio frequency (RF) amplitude was set to zero volts. Heating of a copper frame with a narrowing to 1 mm over 20 mm at one side was examined in air and in addition surrounded by several liters of gelled saline using fiber-optic thermography. Further heating studies were performed using an artificial hip made of titanium, and an aluminum replica of the hip prosthesis with the same geometry. For the copper specimens, considerable heating (>10 degrees C) in air and in gelled saline (>1.2 degrees C) could be observed. Heating of the titanium specimens was markedly less ( approximately 1 degrees C in air). For the titanium artificial hip no heating could be detected, while the rise in temperature for the aluminum replica was approximately 2.2 degrees C. Heating of more than 10 degrees C solely due to gradient switching without any RF irradiation was demonstrated in isolated copper wire frames. Under specific conditions (high gradient duty cycle, metallic loop of sufficient inductance and low resistance, power matching) gradient switching-induced heating of conductive specimens must be considered.


Mycobacterium tuberculosis ESAT6 modulates host innate immunity by downregulating miR-222-3p target PTEN.
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, and it is instant to discover novel anti-TB drugs due to the rapidly growing drug-resistance TB. Mycobacterium tuberculosis (Mtb) secreted effector ESAT6 plays a critical role in modulation miRNAs to regulate host defense mechanisms during Mtb infection, it can be a possible target for new tuberculosis drugs. The non-tuberculous mycobacteria Mycobacterium smegmatis (M. smegmatis) and Mtb have high gene homology but no pathogenicity. We used ESAT6 to interfere with macrophages or mice infected by M. smegmatis and determined that it enhanced the survival rate of bacteria and regulated miR-222-3p target PTEN. Expression of miR-222-3p reduced and PTEN enhanced with the progression of macrophages infected by M. smegmatis with ESAT6 co-incubation. MiR-222-3p overexpression diminished M. smegmatis survival and upregulated proinflammatory cytokines. VO-Ohpic trihydrate (PTEN inhibitor) reduced M. smegmatis survival and upregulated proinflammatory cytokines in vivo and in vitro, and VO-Ohpic trihydrate reversed the tissue damage of mouse organs caused by ESAT6. These results uncover an ESAT6 dependent role for miR-222-3p and its target PTEN in regulating host immune responses to bacterial infection and may provide a potential site for the development of anti-tuberculosis drugs that specifically antagonize the virulence of ESAT6.


Decreased bone turnover in oral contraceptive users.
The objective of this study was to determine the effect of oral contraceptive pills on bone turnover. The design consisted of a cross-sectional analysis of a prospective cohort. There were 52 women taking oral contraceptives and 156 nonuser controls from a large cohort of 1039 healthy women, aged 31-89 years (OFELY study). Most users were taking combined oral contraceptives containing 30 micrograms ethinyl estradiol and the mean duration of pill use was 6.7 +/- 6.4 years. Users and nonusers were matched for age [mean age (years): 39.3 +/- 3.5 vs. 40.5 +/- 4.3, range 35-49 years for both]. Main outcome measures included three markers of bone formation (serum osteocalcin, bone-specific alkaline phosphatase, and C-terminal propeptide of type I collagen) and two markers of bone resorption that are pyridinoline crosslinked peptides (Crosslaps and NTX). Users and nonusers did not differ for weight, height, alcohol and tobacco use, dietary calcium intake, parity, exercise activity, body fat and lean composition, and calcium chemistry tests. In pill users all bone formation and resorption markers were decreased compared with controls: osteocalcin, 7.7 +/- 2.7 vs. 10.1 +/- 3.1 ng/mL (-24%, p < 0.001); bone-specific alkaline phosphatase, 7.5 +/- 2.3 vs. 8.8 +/- 2.7 ng/mL (-15%, p < 0.003); C-terminal propeptide of type I collagen, 77.2 +/- 93.1 vs. 93.1 +/- 31.9 ng/mL (-17%, p = 0.001); Crosslaps: 175 +/- 91 vs. 211 +/- 105 micrograms/mmol Cr (-17%, p = 0.03); and NTX, 16.2 +/- 5.9 vs. 22.5 +/- 9.4 nmol of bone collagen equivalent/mmol Cr (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Brix protein APPAN plays a role in ribosomal RNA processing in Arabidopsis.
Arabidopsis APPAN is a Brix family protein that is homologous to yeast Ssf1/Ssf2 and PPan in higher eukaryotes. A previous study, mostly based on physiological experiments, revealed that APPAN plays an essential role in female gametogenesis in plants. Here, we investigated cellular functions of APPAN, which could be the molecular basis for developmental defects in snail1/appan mutants. Virus-induced gene silencing (VIGS) of APPAN in Arabidopsis resulted in abnormal shoot apices, leading to defective inflorescences and malformed flowers and leaves. APPAN is localized in the nucleolus and co-sedimented mainly with 60 S ribosome subunit. RNA gel blot analyses showed overaccumulation of processing intermediates, particularly 35 S and P-A3, and the sequences were confirmed by circular RT-PCR. These results suggested that silencing of APPAN causes defective pre-rRNA processing. Metabolic rRNA labeling showed that APPAN depletion mainly reduced 25 S rRNA synthesis. Consistently, based on the ribosome profiling, the levels of 60 S/80 S ribosomes were significantly reduced. Finally, APPAN deficiency caused nucleolar stress with abnormal nucleolar morphology and translocation of nucleolar proteins into the nucleoplasm. Collectively, these results suggest that APPAN plays a crucial role in plant rRNA processing and ribosome biogenesis, and its depletion disrupts plant growth and development.


The role of trivalent dimethylated arsenic in dimethylarsinic acid-promoted skin and lung tumorigenesis in mice: tumor-promoting action through the induction of oxidative stress.
We investigated the relationship between lung- and skin-tumor promotion and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. The incidence of lung tumors induced by lung tumor initiator (4NQO) and DMA(V) were, as well as 8-oxo-2'-deoxyguanosine (8-oxodG), suppressed by cotreatment with (-)epigallocatechin gallate (EGCG). When mice were topically treated with trivalent dimethylated arsenic (DMA(III)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed. These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(III) through the induction of oxidative stress.


Quality assessment of cardiac magnetic resonance myocardial scar imaging prior to ventricular arrhythmia ablation.
High-resolution scar characterization using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) is useful for guiding ventricular arrhythmia (VA) treatment. However, imaging study quality may be degraded by breath-holding difficulties, arrhythmias, and implantable cardioverter-defibrillators (ICDs). We evaluated the effect of image quality on left ventricle (LV) base to apex scar interpretation in pre-VA ablation LGE-CMR. 43 consecutive patients referred for VA ablation underwent gradient-recalled-echo LGE-CMR. In ICD patients (n = 24), wide-bandwidth inversion-recovery suppressed ICD artifacts. In non-ICD patients, single-shot steady-state free-precession LGE-CMR could also be performed to reduce respiratory motion/arrhythmia artifacts. Study quality was assessed for adequate/limited scar interpretation due to cardiac/respiratory motion artifacts, ICD-related artifacts, and image contrast. 28% of non-ICD patients had studies where image quality limited scar interpretation in at least one image compared to 71% of ICD patient studies (p = 0.012). A median of five image slices had limited quality per ICD patient study, compared to 0 images per non-ICD patient study. Poorer quality in ICD patients was largely due to motion-related artifacts (54% ICD vs 6% non-ICD studies, p = 0.001) as well as ICD-related image artifacts (25% of studies). In VA ablation patients with ICDs, conventional CMR protocols frequently have image slices with limited scar interpretation, which can limit whole-heart scar assessment. Motion artifacts contribute to suboptimal image quality, particularly in ICD patients. Improved methods for motion and ICD artifact suppression may better delineate high-resolution LGE scar features of interest for guiding VA ablation.


Alterations in serum levels, anti-tumor activity and toxicity of methotrexate in rats after a short period of nutritional depletion.
The alterations in serum levels, anti-tumor activity and host toxicity of methotrexate (MTX) were tested in tumor bearing rats following a period of dietary manipulation. A protein deprived (PD) diet or a diet containing a normal protein content (NP) was administered for 5 days and MTX injected intra-peritoneally (i.p.) at the end of the 5 day period. The MTX serum levels were significantly elevated in rats which received the PD diet, as compared to NP dietary rats. This elevation correlated with an enhanced tumor response to MTX administration. In addition, bone marrow toxicity and intestinal tract toxicity, measured with flow cytometry (FCM) of the bone marrow and morphometry of the jejunal mucosa respectively was increased in rats receiving the PD diet. These results indicate that the serum clearance of MTX is delayed in animals suffering from malnutrition, leading to both enhanced tumor response and increased host toxicity.