Epithelial-stromal communication via CXCL1-CXCR2 interaction stimulates growth of ovarian cancer cells through p38 activation.
Paracrine interactions with the stromal environment, including fibroblasts, may be important in the pathogenesis of ovarian cancer. Here, we evaluated the effect of conditioned media derived from ovarian fibroblasts (fibroblast-CMs) and their major cytokines on the growth of ovarian cancer cells, as well as the involvement of mitogen-activated protein kinases (MAPKs) and AKT in mediating this effect. Ovarian cancer cells were cultured in serum-free media (SF), or conditioned media of fibroblasts derived from normal ovary (CM1) and ovarian tumor tissue (CM2). Cell proliferation was measured by MTT assay. Phosphorylation of MAPKs and AKT was evaluated by Western blotting. Specific inhibitors of MAPKs and AKT were used to evaluate their respective involvement in mediating increased cell growth. Cytokine levels in fibroblast-CMs were measured using Luminex assays. Immunohistochemical staining was conducted for CXCL1, CXCR2 and phosphorylated p38 in primary ovarian tumors. CM1 and CM2 significantly increased the growth of ovarian cancer cells relative to SF. In OVCAR3 and OVCAR4 cells, p38 phosphorylation was strongly induced by fibroblast-CMs, and pre-treatment with a p38 inhibitor prevented the growth increase induced by fibroblast-CMs. Fibroblasts secreted high levels of IL-6, IL-8, MCP1 and CXCL1. Treatment with only CXCL1 (1 μg/ml) increased cell growth and p38 phosphorylation. Treatment with a CXCR2 inhibitor effectively prevented p38 activation and cell growth induced by fibroblast-CMs. High expression of both CXCL1 and CXCR2 correlated with high expression of phosphorylated p38 in primary ovarian tumors. From our data, we conclude that CXCL1 is a key factor derived from ovarian fibroblasts that is responsible for increased ovarian cancer cell growth in part through p38 activation. Phosphorylated p38 can be used as a biomarker to predict CXCL1-CXCR2 interaction in vivo.


[Image-guided bone consolidation in oncology: Cementoplasty and percutaneous screw fixation].
Bone metastases are a common finding in oncology. They often induce pain but also fractures which impair quality of life, especially when involving weight-bearing bones. Percutaneous image-guided consolidation techniques play a major role for the management of bone metastases. Cementoplasty aims to stabilize bone and control pain by injecting acrylic cement into a weakened bone. This minimally invasive technique has proven its efficacy for bones submitted to compression forces: vertebra, acetabular roof, and condyles. However, long bone diaphysis should be treated with caution due to lower resistance of the cement subject to torsional forces. The recent improvements of navigation systems allow percutaneous image-guided screw fixation without requiring open surgery. This fast-track procedure avoids postponing introduction of systemic therapies. If needed, cementoplasty can be combined with screw insertion to ensure better anchoring in major osteolysis. Interventional radiology bone consolidation techniques increase the therapeutic field in oncology. A multidisciplinary approach remains mandatory to select the best indications.


Sharp dose profiles for high precision proton therapy using strongly focused proton beams.
The main objective of radiotherapy is to exploit the curative potential of ionizing radiation while inflicting minimal radiation-induced damage to healthy tissue and sensitive organs. Proton beam therapy has been developed to irradiate the tumor with higher precision and dose conformity compared to conventional X-ray irradiation. The dose conformity of this treatment modality may be further improved if narrower proton beams are used. Still, this is limited by multiple Coulomb scattering of protons through tissue. The primary aim of this work was to develop techniques to produce narrow proton beams and investigate the resulting dose profiles. We introduced and assessed three different proton beam shaping techniques: (1) metal collimators (100/150 MeV), (2) focusing of conventional- (100/150 MeV), and (3) focusing of high-energy (350 MeV, shoot-through) proton beams. Focusing was governed by the initial value of the Twiss parameter [Formula: see text] ([Formula: see text]), and can be implemented with magnetic particle accelerator optics. The dose distributions in water were calculated by Monte Carlo simulations using Geant4, and evaluated by target to surface dose ratio (TSDR) in addition to the transverse beam size ([Formula: see text]) at the target. The target was defined as the location of the Bragg peak or the focal point. The different techniques showed greatly differing dose profiles, where focusing gave pronouncedly higher relative target dose and efficient use of primary protons. Metal collimators with radii [Formula: see text] gave low TSDRs ([Formula: see text]) and large [Formula: see text]([Formula: see text]). In contrast, a focused beam of conventional ([Formula: see text]) energy produced a very high TSDR ([Formula: see text]) with similar [Formula: see text] as a collimated beam. High-energy focused beams were able to produce TSDRs [Formula: see text] and [Formula: see text] around 1.5 mm. From this study, it appears very attractive to implement magnetically focused proton beams in radiotherapy of small lesions or tumors in close vicinity to healthy organs at risk. This can also lead to a paradigm change in spatially fractionated radiotherapy. Magnetic focusing would facilitate FLASH irradiation due to low losses of primary protons.


Use of micellar electrokinetic chromatography to measure palmitoylation of a peptide.
Palmitoylation is the thioester linkage of the fatty acid, palmitate (C16:0), to cysteine residues on a protein or peptide. This dynamic and reversible post-translational modification increases the hydrophobicity of proteins/peptides, facilitating protein-membrane interactions, protein-protein interactions and intracellular trafficking of proteins. Manipulation of palmitoylation provides a new mechanism for control over protein location and function, which may lead to better understanding of cell signaling disorders, such as cancer. Unfortunately, few methods exist to quantitatively monitor protein or peptide palmitoylation. In this study, a capillary electrophoresis-based assay was developed, using MEKC, to measure palmitoylation of a fluorescently-labeled peptide in vitro. A fluorescently-labeled peptide derived from the growth-associated protein, GAP-43, was palmitoylated in vitro using palmitoyl coenzyme A. Formation of a doubly palmitoylated GAP-peptide product was confirmed by mass spectrometry. The GAP-peptide substrate was separated from the palmitoylated peptide product in less than 7 min by MEKC. The rate of in vitro palmitoylation with respect to reaction time, GAP-peptide concentration, pH, and inhibitor concentration were also examined. This capillary electrophoresis-based assay for monitoring palmitoylation has applications in biochemical studies of acyltransferases and thioesterases as well as in the screening of acyltransferase and thioesterase inhibitors for drug development.


Carcinoma of the head of the pancreas. Therapeutic implications of endoscopic retrograde cholangiopancreatography findings.
During a 10-yr period starting January 1973, 123 patients with a carcinoma at the head of the pancreas underwent endoscopic retrograde cholangiopancreatography at our hospital. Analysis of their case histories revealed that the early complaints of pancreatic head carcinoma are rather nonspecific--sudden onset of diabetes mellitus (33.3%), weight loss (80.5%), tiredness and malaise (42.3%), change in bowel habits (41.5%), and upper abdominal discomfort (22.0%)--and that jaundice (88.6%) and classic pain (70.7%) are late symptoms. The diagnostic accuracy of endoscopic retrograde cholangiopancreatography (92.7%) was much higher than that of computed tomography (58.5%) and echography (54.4%). The patients were divided according to the maximal tumor diameter into three groups: group 1, tumor diameter ranging between 2.5 and 4.0 cm; group 2, tumor diameter ranging between 4.5 and 6.0 cm; and group 3, tumor diameter ranging between 7.0 and 15.0 cm. The tumor diameter did not correlate with the degree of differentiation. Extension of the tumor, vascular involvement, and metastases were evaluated for the several tumor diameters. The tumor was, in principle, operable in 77% of group 1 patients; in 24% of group 2 patients; and in 9% of group 3 patients. Tumors less than 3 cm in diameter were always resectable; tumors greater than 8 cm in diameter were seldom (9%) resectable. A curative resection was performed in 22.0% of the patients. The 4-yr survival of these patients was 44% as opposed to no survivors among the patients who had received only palliative or symptomatic treatment. During the decade, there was a tendency toward the diagnosis of smaller tumors (mean tumor diameter decreased from 9.0 +/- 1.7 to 5.4 +/- 2.8 cm) with a higher chance of resectability (from 25% to 44%).


Effect of rapid modulation of circulating plasma testosterone concentration on begging, aggressive behavior and competition for food in black-headed gull (Larus ridibundus) chicks.
Sibling competition mediated by begging behavior is extremely common in avian species and recent studies have highlighted the role of endogenous testosterone in regulating such phenomenon. However, current literature depicts an inconsistent pattern in altricial vs. semi-precocial species, with stimulating versus inhibitory effects of the hormone respectively. This is possibly due to a difference in the methodology of hormone treatment (short-term moderate dose versus a long-term stronger elevation, respectively) between the studies performed so far. In this study, we induced short-term moderate peaks in plasma testosterone levels, as applied in altricial bird species, and assessed the effects of our manipulation on begging, competitive and aggressive behavior in black-headed gull (Larus ridibundus) chicks, a semi-precocial species. Our results suggest that, unlike in altricial songbirds, temporary increase of plasma testosterone concentration suppresses begging and enhances aggressiveness towards intruders. However, it also increases aggression and the chances of getting priority while scrambling with nest mates to gain access to food. Thus, the inconsistencies in the hormonal control of begging behavior observed between altricial vs. semi-precocial birds seem real and perhaps related to species differences in complexity of the display and the nature of competition. These may be elucidated by future comparative studies.


Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis.
ATTR amyloidosis is one of the worldwide most abundant forms of systemic amyloidosis. The disease is caused by the misfolding of transthyretin protein and the formation of amyloid deposits at different sites within the body. Here, we present a 2.97 Å cryo electron microscopy structure of a fibril purified from the tissue of a patient with hereditary Val30Met ATTR amyloidosis. The fibril consists of a single protofilament that is formed from an N-terminal and a C-terminal fragment of transthyretin. Our structure provides insights into the mechanism of misfolding and implies the formation of an early fibril state from unfolded transthyretin molecules, which upon proteolysis converts into mature ATTR amyloid fibrils.


"Needlescopic" sigmoid resection.
Minimally invasive surgical techniques and procedures continue to evolve with the trend toward fewer and smaller instruments. To our knowledge, this is the first reported case of sigmoid colon resection utilizing needlescopic technology. The patient was a 53-year-old woman diagnosed with a malignant lesion in the midsigmoid colon at 30 cm. A subsequent needlescopic sigmoid colon resection was performed and the patient was discharged home after an uneventful postoperative course. This case demonstrates that colon procedures that require major reconstruction may be performed needlescopically in selected patients.


Valve replacement in children and adolescents.
Replacement of diseased heart valves has become the treatment of choice in many adults. Valve replacement in older children and adolescents has been done in our institution only when other procedures are ineffective. Over the past 10 years, 24 patients have received 28 artificial valves. Thirteen (54 per cent) had rheumatic heart disease; the remainder had congenital or acquired valvular abnormalities. The Björk-Shiley valve was most commonly used in the aortic position and the Beall prosthesis in the mitral position. Sixteen patients (67 per cent) survived operation and have been followed from 3 to 79 months, averaging 27 months. All are free of cardiac symptoms. Hemarthrosis occurred once in 2 survivors (13 per cent). Eight patients died (33 per cent), 5 immediately postoperatively and 3 within a year after the operation. The mortality rate has declined to 21 percent during the past 3 years. Our experience in the pediatric age group suggests that valve replacement is a serious undertaking with higher mortality rate than in adults. The operation should be reserved for those patients in whom valvuloplasty or valvulotomy is expected to be ineffective.


Therapeutic frontiers: preventing and treating infectious diseases by inhibiting bacterial quorum sensing.
Density-dependent cell-cell communication, or quorum sensing (QS), has been demonstrated in numerous species of bacteria. The basic function of QS is likely to confer a nutritional advantage, particularly in a highly populated, mixed-species environment. QS also has ramifications on the production of colonization and virulence factors. Pheromone-like substances secreted into the extracellular milieu appear to govern many of the transcription products in these bacteria. At a high cell density, the QS systems are triggered, and the transcription of the colonization factors are suppressed and replaced by the expression of virulence factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems. Several QS-modulating therapies, such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have been investigated and may prove to be helpful in diminishing the translation of QS-directed toxins or by prematurely activating the QS response to alert the immune system to bacteria hiding in a low cell density. QS represents a recently discovered method of bacterial communication and population control, which may prove to be a unique mechanism to prevent, suppress, and/or treat infectious diseases.


Segmentation of 3D EBSD data for subgrain boundary identification and feature characterization.
Subgrain structures formed during plastic deformation of metals can be observed by electron backscatter diffraction (EBSD) but are challenging to identify automatically. We have adapted a 2D image segmentation technique, fast multiscale clustering (FMC), to 3D EBSD data using a novel variance function to accommodate quaternion data. This adaptation, which has been incorporated into the free open source texture analysis software package MTEX, is capable of segmenting based on subtle and gradual variation as well as on sharp boundaries within the data. FMC has been further modified to group the resulting closed 3D segment boundaries into distinct coherent surfaces based on local normals of a triangulated surface. We demonstrate the excellent capabilities of this technique with application to 3D EBSD data sets generated from cold rolled aluminum containing well-defined microbands, cold rolled and partly recrystallized extra low carbon steel microstructure containing three magnitudes of boundary misorientations, and channel-die plane strain compressed Goss-oriented nickel crystal containing microbands with very subtle changes in orientation.


Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury.
To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI). Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schramek's grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schramek's grading. The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy. MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patient's level of satisfaction with the quality of the erection compared with intracavernosal injections.


The histone H5 variant in Xenopus laevis.
The presumptive histone H5 of Xenopus laevis has been characterized by SDS and acid-urea-Triton polyacrylamide gel electrophoresis and compared with chicken histone H5. Chicken H5 has a lower electrophoretic mobility compared to that of Xenopus H5 in both gel systems. It is shown, using a polyclonal antiserum against chicken H5, that the Xenopus histone H5 is immunologically related to chicken histone H5. Monoclonal antibodies have been prepared to the Xenopus histone types H5 and H1A, that do not cross-react, as determined by their reactivity in an enzyme linked immunosorbent assay and by their ability to react with either H1A or H5 in an immunochemical test on total erythrocyte histones that are transferred to nitrocellulose after fractionation by SDS- or acid-urea polyacrylamide gel electrophoresis. As all nuclei of erythrocytes from adult Xenopus laevis can be shown to contain histone H1A and H5, these monoclonal antibodies can be used to further delineate the role of H5 in tissue differentiation.


Unraveling the anti-corrosion mechanisms of a novel hydrazone derivative on steel in contaminated concrete pore solutions: An integrated study.
Corrosion-induced deterioration of infrastructure is a growing global concern. The development and application of corrosion inhibitors are one of the most effective approaches to protect steel rebar from corrosion. Hence, this study focuses on a novel hydrazone derivative, (E)-N'-(4-(dimethylamino)benzylidene)-2-(5-methoxy-2-methyl-1H-indol-3-yl)aceto-hydrazide (HIND), and its potential application to mitigate corrosion in steel rebar exposed to chloride-contaminated concrete pore solutions (ClSCPS). The research aims to evaluate the anti-corrosion capabilities of HIND on steel rebar within a simulated corrosive environment, focusing on the mechanisms of its inhibitory effect. The corrosion of steel rebar exposed to the ClSCPS was studied through weight loss and electrochemical methods. The surface morphology of steel rebar surface was characterized by FE-SEM-EDS, AFM; oxidation states of the steel rebar and crystal structures were examined using X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) methods. Further, experimental findings were complemented by theoretical studies using self-consistent-charge density-functional tight-binding (SCC-DFTB) simulations. The performance of HIND was monitored at an optimal concentration over a period of 30 days. The results indicated a significant reduction in steel rebar corrosion upon introducing HIND. The inhibitor molecules adhered to the steel surface, preventing further deterioration and achieving an inhibition efficiency of 88.4% at 0.5 mmol/L concentration. The surface morphology analysis confirmed the positive effect of HIND on the rebar surface, showing a decrease in the surface roughness of the steel rebar from 183.5 in uninhibited to 50 nm in inhibited solutions. Furthermore, SCC-DFTB simulations revealed the presence of coordination between iron atoms and HIND active sites. The findings demonstrate the potential of HIND as an effective anti-corrosion agent in chloride-contaminated environments. Its primary adsorption mechanism involves charge transfer from the inhibitor molecules to iron atoms. Therefore, applying HIND could be an effective strategy to address corrosion-related challenges in reinforced infrastructure.


Monitoring demineralization and remineralization of human dentin by characterization of its structure with resonance-enhanced AFM-IR chemical mapping, nanoindentation, and SEM.
This research aimed at monitoring demineralization and remineralization of dentin and its collagen matrix at the nanoscale by amorphous, microcrystalline, and in situ formed hydroxyapatite. The concurrent use of the resonance-enhanced atomic force microscopy coupled with infrared probe (AFM-IR) chemical mapping, nano-indentation, and scanning electron microscopy (SEM) provides a detailed insight into the structure of human dentin, as well as to the processes of its partial demineralization and remineralization. The resonance-enhanced AFM-IR chemical mapping of dentin has shown to be a useful method to follow distribution of its collagen and hydroxyapatite components at the micro- and nanoscale levels, especially in conjunction with SEM imaging and nanoindentation. Dentin with a higher extent of natural dentin tubule occlusion tends to be harder and less elastic. The relative affinity of the collagen and hydroxyapatite components of dentin toward hydroxyapatite depends on its type (amorphous, microcrystalline, or formed in-situ). The gel mineralization technique allows for an even and controlled growth of hydroxyapatite guided by the completely demineralized collagen matrix of dentin. The observed trends of the affinity of collagen toward different forms of hydroxyapatite helps develop new remineralizing formulations. The employed methods of characterization may provide an insight to the natural processes of bone mineralization guided by its both hydroxyapatite and protein constituents.


Saccadic eye movement metrics reflect surprise and mental model updating.
Two experiments investigated what eye movements can reveal about how we process surprising information and how we update mental models in dynamic and unstructured environments. Participants made saccades to visual targets presented one at a time, radially, around an invisible perimeter. Target locations were normally distributed and shifted at an unannounced point during the task. Trials following the shift were considered surprising and unexpected. These unexpected and surprising events prompted the need to update. Slower saccadic latencies were observed for surprising/unexpected events, perhaps indicative of the need to reorient attention to the unexpected target location. Longer dwell times were observed for events that signaled a change in the distribution. These data show that eye movement metrics provide a reliable indicator of mental model updating when contingencies change even in the absence of explicit change signals.


Renal-portal vein shunt for renal failure after left renal vein ligation in children: a review.
Interruption of the inferior vena cava and left renal vein in the patient with a solitary left kidney without permanent renal damage has been reported in the past. We assess the risks of similar venous interruption in children and establish guidelines for the management of those cases when collateral drainage of the kidney is uncertain. We compared our case with a review of all previous reports in the literature concerning ligation of the vena cava and left renal vein in patients with a solitary left kidney. Ligation of the left renal vein in an isolated left kidney in children has been shown to carry the risk of significant renal damage. Renal-portal vein shunt provided adequate drainage of the left kidney after inferior vena caval ligation in our case. While there have been reported cases of successful inferior vena cava or left renal vein ligation in the isolated left kidney with good renal function, adequate renal drainage should be established in cases where collateral drainage is uncertain, especially in children. Renal-portal vein shunt is a viable therapeutic option to establish left renal drainage in select circumstances.


Serum and urine levels of phenol following phenol blocks.
In 20 patients with chronic peripheral vascular disease measurement was made of serum and urine phenol concentrations after lumbar or thoracic sympathetic block with 4-10 ml of seven per cent aqueous phenol. Peak concentration times (tmax), peak concentrations (Cmax), lag times (Tlag), apparent elimination half-lives (t1/2el), and areas under the serum concentration curves (AUC) were determined. The values of tmax, Cmax, Tlag, t1/2el, and AUC were 18.8 +/- 2.5 min, 3.01 +/- 0.28 microgram X ml-1, 5.3 +/- 1.6 min, 30.3 +/- 2.8 min, and 365 +/- 41 micrograms X ml-1 X min-1, respectively, for unconjugated phenol. Values for conjugated phenol were 54.9 +/- 4.5 min, 4.15 +/- 0.25 microgram X ml-1, 9.9 +/- 5.9 min, 64.0 +/- 7.3 min, and 838 +/- 95 micrograms X ml-1 X min-1, respectively. The cumulative urinary excretion in the conjugated form within 8 h ranged from 31 to 63 per cent of the dose administered. The results indicate that phenol has a very short half-life and is excreted quickly into the urine, conjugated with sulfate.


N-acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators.
N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) was originally reported as a natural inhibitor of the proliferation of stem cells. To elucidate whether Ac-SDKP inhibits the proliferation of human mesangial cells, we examined the effect of Ac-SDKP on fetal calf serum (FCS)- or platelet-derived growth factor (PDGF)-BB-induced DNA synthesis and a cell proliferation. Ac-SDKP inhibited PDGF-BB- or FCS-induced DNA synthesis without cellular toxicity. The protein expression of p53 and p27kip1 was significantly increased by Ac-SDKP. Ac-SDKP also up-regulated the PDGF-BB-stimulated expression of p21cip1 and suppressed PDGF-BB-induced cyclin D1 expression. In p53 knock-out human mesangial cells made with small interference RNA, the protein expression of p21cip1 and p27kip1 was also decreased and the inhibitory effect of Ac-SDKP on mesangial proliferation was completely abolished. Ac-SDKP increased the stability of p53 protein as demonstrated by pulse-chase experiment. These results suggest that p53 is the key mediator of Ac-SDKP-induced inhibition of DNA synthesis through the up-regulation of cell cycle modulators, highlighting a potential effect of Ac-SDKP on various progressive renal diseases.


The transsynaptic regulation of the septal-hippocampal cholinergic neurons.
There is not yet a complete understanding of the functional interactions among various septal nuclei which regulate hippocampal function. Nevertheless, much has been learned histologically and biochemically about the major connections of the distinct areas of the septal complex and the chemical character of some of these pathways. The cholinergic septal-hippocampal pathway serves as a well defined link between these two important structures of the limbic system. Acetylcholine turnover rates in the hippocampus have been shown to increase or decrease proportionally to the activity of the cholinergic neurons originating in the septum. Moreover, these turnover rates have been shown to be modulated by intraseptal injections of agonists or antagonists of various neurotransmitters or neuromodulators which are stored in various cell groups located in the septum. By coupling this biochemical approach with techniques to study the receptor organization, greater detail concerning the transmitter and cotransmitter interactions among the various neuromodulators can be obtained.


Blunt cerebrovascular injuries in acute trauma care: a screening protocol.
Blunt cerebrovascular injuries (BCVI) of the extra- or intracerebral vessels are frequently observed lesions which may lead to thrombembolic events with focal neurological deficits, stroke or death particularly in patients <60 years. However, a comprehensive standardised clinical algorithm for screening and management of these secondary injuries is still lacking. We developed a standardised screening protocol applicable for mild as well as severely injured patients. In this prospective cohort study, we evaluated the feasibility of this diagnostic algorithm in a level 1 trauma centre setting. Trauma patients who met the inclusion criteria underwent a computed tomographic angiography (CTA) as part of standard diagnostic procedure at admission. All suspicions or positive findings were reevaluated by a conventional four-vessel catheter angiography within the first 72 h after trauma. Within this period, anticoagulation with low-dose heparin was started. BCVI confirmation indicated a shift to systemic heparinisation with overlapping phenprocoumon therapy for at least 6 months. All patients were reevaluated after 6 months by another four-vessel angiography. Depending on the diagnostic findings, oral anticoagulation may be discontinued or continued for another 6 months. A total of 44 patients (8 male, 6 female, age range 19-95 years) were included in the study. 20 BCVIs were detected in 16 patients (36.3%). The most common injuries identified were Biffl Type II (40%) and Type IV lesions (30%). 86.4% of the patients received a CTA upon admission, 93.2% of which were conducted within 12 h posttrauma. None of the patients had a secondary thrombembolic neurological event during the hospital stay or within 3 months postdischarge. Our results indicate that implementation of the screening protocol can prevent strokes in patients without primary thrombembolic neurological deficits.


Design principles of the human brain: an evolutionary perspective.
The evolution of the brain in mammals has been accompanied by a reorganization of the brain as a result of differential growth of certain brain regions. Consequently, the geometry of the brain, and especially the size and shape of the cerebral cortex, has changed notably during evolution. Comparative studies of the cerebral cortex suggest that there are general architectural principles governing its growth and evolutionary development and that the primate neocortex is uniformly organized and composed of neural processing units. We are beginning to understand the geometric, biophysical, and energy constraints that have governed the evolution of these neuronal networks. In this review, some of the design principles and operational modes will be explored that underlie the information processing capacity of the cerebral cortex in primates, and it will be argued that with the evolution of the human brain we have nearly reached the limits of biological intelligence.


A Safe Number of Perioperative Opioids to Reduce the Risk of New Persistent Usage Among Opioid-Naïve Patients Following Total Joint Arthroplasty.
Higher initial opioid dosing increases the risk of prolonged opioid use following total joint arthroplasty (TJA), and the safe amounts to prescribe are unknown. We examined the relationship between perioperative opioid exposure and new persistent usage among opioid-naïve patients after total knee and hip arthroplasty. In this retrospective cohort study, 22,310 opioid-naïve patients undergoing primary TJA between 2018 and 2019 were identified within a commercial claims database. Perioperative opioid exposure was defined as total dose of opioid prescription in morphine milligram equivalents (MME) between 1 month prior to and 2 weeks after TJA. New persistent usage was defined as at least one opioid prescription between 90 and 180 days postoperatively. Multivariate regression analyses were performed to examine the relationship between the perioperative dosage group and the development of new persistent usage. For the total patient cohort, 8.1% developed new persistent usage. Compared to patients who received <300 MME, patients who received 600-900 MME perioperatively had a 77% increased risk of developing new persistent usage (odds ratio 1.77, 95% CI, 1.44-2.17), and patients who received ≥1,200 MME perioperatively had a 285% increased risk (odds ratio 3.85, 95% CI, 3.13-4.74). We found a dose-dependent association between perioperative MME and the risk of developing new persistent usage among opioid-naïve patients following TJA. We recommend prescribing <600 MME (equivalent to 80 pills of 5 mg oxycodone) during the perioperative period to reduce the risk of new persistent usage. Level III.


Assembly of single molecular magnets from dinuclear to 2D Dy-compounds with significant change of relaxation energy barriers.
A dinuclear Dy(III) compound (1) was structurally and magnetically characterized, displaying a single-molecule magnet (SMM) behavior with a relaxation energy barrier of 21(1) K. Interestingly, by only adding a suitable substituent on the ligand in , as an SMM building unit, can be further assembled into a two-dimensional (2D) framework (2), which possesses a typical SMM behavior and a high relaxation energy barrier of 68(2) K. The result implied that the assembly of an SMM can effectively tune the energy barrier. To our knowledge, a cluster-based SMM assembled into a new 2D framework with SMM behavior is seldom reported.


Controlled growth of Co9S8 nanoparticle-embedded carbon nanosheets/carbon nanofibers toward high-performance sodium storage.
Transition metal sulfides (TMSs) are considered as promising anodes for sodium-ion batteries (SIBs) due to their high theoretical capacity and low cost. However, TMSs suffer from massive volume expansion, slow sodium-ion diffusion kinetics, and poor electrical conductivity, which severely restrict their practical application. Herein, we design self-supporting Co9S8 nanoparticles embedded carbon nanosheets/carbon nanofibers (Co9S8@CNSs/CNFs) as anode materials for SIBs. The electrospun carbon nanofibers (CNFs) provide continuous conductive networks to accelerate the ion and electron diffusion/transport kinetics, while MOFs-derived carbon nanosheets (CNSs) buffer the volume variation of Co9S8, consequently improving the cycle stability. Benefitting from the unique design and pseudocapacitive features, Co9S8@CNSs/CNFs deliver a stable capacity of 516 mAh g-1 at 200 mA g-1 and a reversible capacity of 313 mAh g-1 after 1500 cycles at 2 A g-1. Note that, it also displays excellent sodium storage performance when assembled into a full cell. The rational design and excellent electrochemical properties endow Co9S8@CNSs/CNFs with the potential stepping into commercial SIBs.


Clozapine but not haloperidol antagonizes an MK-801 discriminative stimulus cue.
The noncompetitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801) produced an interoceptive stimulus cue in rats trained to discriminate between MK-801 (0.075 mg/kg) and saline in a two-choice, discrete trial avoidance paradigm. Haloperidol (0.03-0.3 mg/kg) failed to antagonize the discriminative stimulus cue of MK-801, with all rats choosing the MK-801-appropriate choice lever. Higher doses of haloperidol (1.0 mg/kg) produced significant sedation such that the rats were unable to complete all the trials. In contrast, clozapine dose dependently antagoinzed the discriminative stimulus cue produced by MK-801. Clozapine at a dose of 3.0 mg/kg completely antagonized the stimulus cue produced by MK-801. Therefore, the discriminative stimulus cue produced by the noncompetitive NMDA antagonist MK-801 may be useful as an animal model for selecting novel drugs with potential efficacy for treatment-resistant schizophrenia.


Ultrasound evaluation of masseter muscle changes in stabilization splint treatment of myofascial type painful temporomandibular diseases.
To detect whether stabilization splint (SS) treatment of painful myofascial type temporomandibular diseases (TMD) changes the masseter muscle morphology using ultrasound (US). Thirty-five patients with painful myofascial TMD receiving SS treatment were studied. Masseter thickness, length, internal echo-fibrillary structure and vascularization were evaluated using gray-scale and power Doppler US just before and 3 months after the SS application. Visual analog scale (VAS) and mouth opening measurements were used to measure the outcome of treatment. A significant shortening in the masseter muscle length (R: -3.67 mm, P: .010; L: -3.97 mm, P: .005) and thickness (R: -0.93 mm, P: .005; L: -0.90 mm, P: .016) was noted. No change in the internal echo-fibrillary structure or vascularization was detected. A significant decrease in VAS scores (Median: 5-0.5 P < .05) and mouth opening (42.77 ± 7.86 mm to 38.69 ± 6.21, P < .05) was also detected. SSs modify and reduce the dimensions of masseter muscle.


Epidemiology of severe eye injuries in childhood.
The authors conducted a cross-sectional study of all ocular injury cases admitted to a children's hospital between January 1978 and December 1984. Of 222 injuries reviewed, 77 (35%) resulted in some visual deficit. Males were significantly overrepresented in all age groups with an average male:female ratio of 3.5:1. The distribution of injuries was: contusions, 114 (51%); penetrating lacerations, 62 (28%); foreign bodies and burns, 11 (5%); and nonpenetrating lacerations, 35 (16%). Sixteen (7%) ocular injuries were associated with BB gun pellets and six of these children (42%) were blinded in the injured eye as a result. Two other cases of blindness resulted from ocular penetration by homemade "Jinsang Stars," underscoring the adverse influence of media on children's games. Adult supervision could have potentially prevented most cases of permanent visual deficit. The authors suggest that legislation restricting the use of BB guns be passed and that a program of adult and child eye safety education including "eye watch" warnings on potentially hazardous toys be developed.


Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo.
Pentraxin 3 (PTX3) is an inflammatory molecule that is involved in immune responses, inflammation, and cancer. Recent evidence suggests that PTX3 plays a critical role in tumor progression; however, its impact on the biological function of gliomas remains unknown. In the present study, immunohistochemical staining showed that patients with high-grade gliomas exhibited increased expression levels of PTX3 compared to those with low-grade gliomas (P < 0.001). Furthermore, knockdown of PTX3 in GBM8401 cells inhibits proliferation, increases p21 protein levels, and decreases cyclin D1 protein levels, resulting in cell cycle arrest at the G0/G1 phase. In addition, knockdown of PTX3 significantly decreases GBM8401 cell migration and invasion through the downregulation of matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) expression. In a GBM8401 xenograft animal model, PTX3 knockdown decreases tumor growth in vivo. In conclusion, PTX3 plays an important role in glioma cell proliferation and invasion, and may thus serve as a novel potential therapeutic target in the treatment of gliomas.


Judgment tasks in clinical psychiatric mental health nursing.
What are the cognitive tasks involved in making judgments in psychiatric nursing? Fifteen nurses with varied educational preparation provided 36 in-depth interviews. A comparative content analysis was done to determine the underlying structure of judgment tasks. Nurses use clients' presenting behaviors as a basis for making judgments, with judgments being multiple multidimensional, overlapping, and holistic. Understanding judgment tasks delineates the kind of information needed to provide the best possible care.


Renal and perirenal infection: the role of computerized tomography.
Predisposing factors, onset of symptoms to diagnosis interval, computerized tomography findings and the impact of computerized tomography on the outcome were studied retrospectively in 24 patients with renal or perirenal infections. The most common predisposing factors were diabetes mellitus and urinary tract calculi. The mean interval from the onset of symptoms to diagnosis was 6.8 days. The most common computerized tomography findings were thickening of Gerota's fascia, renal enlargement, focal decreased renal attenuation, perirenal fluid and focal gas. Four patients died despite early diagnosis and appropriate therapy. Computerized tomography aided in the diagnosis, assessment of the extent of disease, treatment and followup. Computerized tomography is the most direct method to evaluate patients with suspected renal or perirenal infection, although mortality may not be altered significantly.


Constant current source for iontophoresis.
A simple, battery-powered current source is described that is suitable for the iontophoresis of axonal tracing substances, such as Phaseolus vulgaris leucoagglutinin. Unlike the previous designs that form the basis of most commonly used iontophoretic devices, this circuit does not use operational amplifiers to provide controlled current. Instead, a pair of bipolar transistors that can be selected to provide a compliance of many hundreds of volts form the regulating circuitry.


Silver and gold nanoparticles characterization by SP-ICP-MS and AF4-FFF-MALS-UV-ICP-MS in human samples used for biomonitoring.
The rapid increase in the use of silver (Ag) and gold (Au) nanoparticles (NPs) can be a potential risk to humans. Ag and Au NPs may enter the blood, accumulate in organs and be cleared from the body. It is therefore necessary to develop detection and quantification methods for Ag and Au NPs in human matrices. To this end, the inductively coupled plasma mass spectrometry was used as single particle detector (SP-ICP-MS) and coupled on-line with asymmetric flow field flow fractionation (AF4-FFF-ICP-MS), multi-angle scattering (MALS) and UV. Both methods enabled the qualitative and quantitative measurement of mixtures of Ag NPs (20, 60 and 100 nm) and Au NPs (5, 20, 40 and 60 nm) in human urine, blood and serum. Methods were validated by estimating linearity, limit of detection, resolution, repeatability, recovery and stability of Ag and Au NPs measurements in fluids. The SP-ICP-MS showed concentration limits for Ag and Au NPs lower than AF4-FFF-ICP-MS (pg/mL vs. ng/mL, respectively), while AF4-FFF-ICP-MS could detect smaller sized NPs (2-5 nm vs. 7-14 nm for SP-ICP-MS) with good resolution between monodispersed NPs fractions. In addition, MALS detector was more promising respect to higher sizes of Ag and Au NPs (>40 nm), while UV for lower sized particle (<20 nm). The observed performances will allow to use ICP-MS-based methods, also coupled to other detectors, to carry out human biomonitoring campaigns dedicated to the analysis of metallic NPs in the general population and in exposed subjects.


Locking the Taylor Spatial Frame - The effect of three additional longitudinal rods on osteotomy site movements.
In clinical practice, even when the fixator is locked, a noticeable laxity of the construct can be observed. This study was designed to measure the stiffness of the fixator and to analyze the movements of the osteotomy site. Furthermore, the effect of three additional longitudinal rods on the locking of the construct was analyzed. Five synthetic tibia/fixator models (Model A) were tested under rotational torque (40 Nm) and axial compression (700 N). Three additional rigid rods were subsequently mounted, and the tests were repeated (Model B). The movements of the fixator as well as the osteotomy site were registered by a digital optical measurement system. Load- deformation curves, and so stiffness of the models, were calculated and compared. Under rotational and axial loadings, Model A was found to be less rigid than Model B (p = 0.034; p = 0.194). Notably, Model A showed a region of laxity around neutral rotational (ΔF = 5 Nm) and axial (ΔF = 16.64 N) loading before a linear deformation trend was measured. Concomitantly, greater osteotomy site movement was measured for Model A than for Model B under full loading (p = 0.05) and within the region of increased laxity (p = 0.042). The fixator showed an element of laxity around neutral axial and rotational loading, which transferred to the bone and led to a notable amount of osteotomy gap movement. Mounting three additional rods increased the stiffness of the construct and therefore reduced the movement of the osteotomy site.


Visceral fat mass as a novel risk factor for predicting gestational diabetes in obese pregnant women.
To develop a model to predict gestational diabetes mellitus incorporating classical and a novel risk factor, visceral fat mass. Three hundred two obese non-diabetic pregnant women underwent body composition analysis at booking by bioimpedance analysis. Of this cohort, 72 (24%) developed gestational diabetes mellitus. Principal component analysis was initially performed to identify possible clustering of the gestational diabetes mellitus and non-GDM groups. A machine learning algorithm was then applied to develop a GDM predictive model utilising random forest and decision tree modelling. The predictive model was trained on 227 samples and validated using an independent testing subset of 75 samples where the model achieved a validation prediction accuracy of 77.53%. According to the decision tree developed, visceral fat mass emerged as the most important variable in determining the risk of gestational diabetes mellitus. We present a model incorporating visceral fat mass, which is a novel risk factor in predicting gestational diabetes mellitus in obese pregnant women.


Effect of chlordecone on pH and temperature dependent substrate activation kinetics of rat brain synaptosomal ATPases.
Chlordecone, a polycyclic chlorinated insecticide known as Kepone, inhibited the activities of (Na+-K+)ATPase and Mg2+-ATPase in rat brain synaptosomes. Altered pH and specific activity curves for both enzymes demonstrated significant inhibition by chlordecone in buffered acidic, neutral and alkaline pH ranges. Noncompetitive inhibition with respect to activation by ATP in the case of (Na+-K+)ATPase was indicated by altered Vmax values with no significant change in Km values at any pH studied, except at pH 9.5. Mg2+-ATPase was inhibited uncompetitively as evidenced by altered Vmax and Km values. The activities of both ATPase were decreased in the presence of chlordecone at higher temperatures. Activation energy (delta E) values were found to be decreased significantly in the presence of chlordecone at 37 degrees. Arrhenius plots of both ATPases preincubated with chlordecone were found to be nonlinear. In the presence of chlordecone, Vmax was decreased without significant change in Km values for (Na+-K+)ATPase at all temperatures, suggesting a noncompetitive type of inhibition. In the case of Mg2+-ATPase, similar noncompetitive type inhibition was obtained at 27 degrees but not at 32 and 37 degrees. The kinetic data in general suggest that the chlordecone inhibited (Na+-K+)ATPase noncompetitively and Mg2+-ATPase uncompetitively at all pHs and temperatures studied. The present data suggest that inhibition of (Na+-K+)ATPase and Mg2+-ATPase, the two membrane-bound enzymes in synaptosomes, by chlordecone is temperature dependent and pH independent.


Modeling optimal treatment strategies in a heterogeneous mixing model.
Many mathematical models assume random or homogeneous mixing for various infectious diseases. Homogeneous mixing can be generalized to mathematical models with multi-patches or age structure by incorporating contact matrices to capture the dynamics of the heterogeneously mixing populations. Contact or mixing patterns are difficult to measure in many infectious diseases including influenza. Mixing patterns are considered to be one of the critical factors for infectious disease modeling. A two-group influenza model is considered to evaluate the impact of heterogeneous mixing on the influenza transmission dynamics. Heterogeneous mixing between two groups with two different activity levels includes proportionate mixing, preferred mixing and like-with-like mixing. Furthermore, the optimal control problem is formulated in this two-group influenza model to identify the group-specific optimal treatment strategies at a minimal cost. We investigate group-specific optimal treatment strategies under various mixing scenarios. The characteristics of the two-group influenza dynamics have been investigated in terms of the basic reproduction number and the final epidemic size under various mixing scenarios. As the mixing patterns become proportionate mixing, the basic reproduction number becomes smaller; however, the final epidemic size becomes larger. This is due to the fact that the number of infected people increases only slightly in the higher activity level group, while the number of infected people increases more significantly in the lower activity level group. Our results indicate that more intensive treatment of both groups at the early stage is the most effective treatment regardless of the mixing scenario. However, proportionate mixing requires more treated cases for all combinations of different group activity levels and group population sizes. Mixing patterns can play a critical role in the effectiveness of optimal treatments. As the mixing becomes more like-with-like mixing, treating the higher activity group in the population is almost as effective as treating the entire populations since it reduces the number of disease cases effectively but only requires similar treatments. The gain becomes more pronounced as the basic reproduction number increases. This can be a critical issue which must be considered for future pandemic influenza interventions, especially when there are limited resources available.


Small-scale techniques for the analysis of recombinant plasmids.
Using the cloning of part of the T-DNA of pTiC58 from Agrobacterium tumefaciens as an example, techniques are described which enable recombinant plasmids to be mapped and used as hybridization probes. In all cases the starting material is a colony of cells grown on an agar plate which is then subjected to lysis by lysozyme and Triton X-100 in volumes of the order of 300 microliters thus eliminating the need for handling and centrifuging liquid cultures under restrictive containment conditions.


Degradation of bio-based and biodegradable plastics in a salt marsh habitat: Another potential source of microplastics in coastal waters.
Degradation of bio-based (polylactic acid [PLA] cups, Mater-Bi® [MB] bags) and biodegradable plastics (biodegradable extruded polystyrene [bioPS] plates, biodegradable high density polyethylene [bioHDPE] bags) were compared to conventional plastics (recycled polyethylene terephthalate [rPET] cups, HDPE bags, extruded PS plates) in a salt marsh over a 32-week period. Following 4 weeks, biofilm developed on all plastics, resulting in an increased weight and concomitant decrease in UV transmission for most plastics. All plastics produced microplastic particles beginning at 4 weeks, with single-use bags producing the most microplastics over the 32-week period. At 32 weeks, SEM revealed microcracks and delamination for all plastics except PLA and MB, the latter of which degraded through embrittlement. IR spectral analysis indicated degradation for all plastics except PLA. Results suggest that degradation rates of bio-based and biodegradable plastics vary widely, with MB bags and bioPS plates demonstrating the greatest degradation, while PLA cups demonstrated the least degradation.


An inducible long noncoding RNA, LncZFHX2, facilitates DNA repair to mediate osteoarthritis pathology.
Cartilage homeostasis is essential for chondrocytes to maintain proper phenotype and metabolism. Because adult articular cartilage is avascular, chondrocytes must survive in low oxygen conditions, and changing oxygen tension can significantly affect metabolism and proteoglycan synthesis in these cells. However, whether long noncoding RNA participate in cartilage homeostasis under hypoxia has not been reported yet. Here, we first identified LncZFHX2 as a lncRNA upregulated under physiological hypoxia in cartilage, specifically by HIF-1α. LncZFHX2 knockdown simultaneously accelerated cellular senescence, targeted multiple components of extracellular matrix metabolism, and increased DNA damage in chondrocytes. Through a series of in vitro and in vivo experiments, we identified that LncZFHX2 performed a novel function that regulated RIF1 expression through forming a transcription complex with KLF4 and promoting chondrocyte DNA repair. Moreover, chondrocyte-conditional knockout of LncZFHX2 accelerated injury-induced cartilage degeneration in vivo. In conclusion, we identified a hypoxia-activated DNA repair pathway that maintains matrix homeostasis in osteoarthritis cartilage.


Clinical pharmacology of extended-spectrum penicillins in infants and children.
Compared with previously available penicillins, piperacillin, azlocillin, and mezlocillin have increased activity in vitro against gram-negative bacilli. After intravenous administration of conventional doses (50 to 100 mg/kg) in children, peak concentrations of these drugs are approximately 70 to 350 micrograms/ml. For piperacillin, azlocillin, and mezlocillin, the half-lives during the beta elimination phase (t 1/2 beta) are approximately 0.5 to 0.75, 0.8 to 1.7, and 0.8 to 1.0 hours, respectively. In patients receiving the higher dosage, particularly of azlocillin, the t 1/2 beta may be prolonged by approximately 20%. A total daily dosage of 300 mg/kg or 9 gm/m2 given in four to six divided dosages should produce peak concentrations of approximately 150 micrograms/ml, and concentrations greater than 16 micrograms/ml for at least 2 hours after each administration. Lower daily dosages are needed in neonates, but precise dosage recommendations cannot be made at this time. Only approximately 60% of piperacillin and approximately 45% of azlocillin are eliminated unchanged in the urine; thus only modest dosage reductions are needed in patients with decreased renal function. In children, adverse effects have been infrequent.


Functional Connectivity Alterations of Cognitive Flexibility in Aging: Different Patterns of Global and Local Switch Costs.
Cognitive flexibility declines with aging and is usually indicated by task switch costs including global and local switch costs. Cognitive flexibility in aging is associated with alterations in functional connectivity. However, whether different task-modulated connectivity mechanisms underlying global and local switch costs remain unclear. Here we use the support vector machine to identify age-related functional connectivity in global and local switch costs between older (n = 32) and young adults (n = 33). Participants completed a cued task-switching task during the functional magnetic resonance imaging scan. Results show an age-related decline behaviorally in global but not in local switch costs. Moreover, distinct patterns of age-related alterations of connectivity were observed for each cost. Specifically, only multivariate changes in connectivity patterns were observed for local switch cost, whereas specific age-related connections were revealed for global switch cost. In older adults, the task-modulated left dorsal premotor cortex-left precuneus connectivity decreased, and the left inferior frontal junction-left inferior parietal sulcus connectivity correlated with decreased global switch cost. This study provides novel evidence for different neural patterns in global and local switch costs by illuminating connectivity mechanisms underlying cognitive flexibility in aging.


Pancreatic pathophysiology in cystic fibrosis.
The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients, due to its early clinical onset, co-morbidities and lack of tissue samples from the early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us to better define the influence of pancreatic lesions on CF disease progression in other organs, such as the gastrointestinal tract and lung.


Basal and induced sphingosine kinase 1 activity in A549 carcinoma cells: function in cell survival and IL-1beta and TNF-alpha induced production of inflammatory mediators.
Sphingosine-1-phosphate, a lipid mediator produced by sphingosine kinases, regulates diverse cellular processes, ranging from cell growth and survival to effector functions, such as proinflammatory mediator synthesis. Using human A549 epithelial lung carcinoma cells as a model system, we observed transient upregulation of sphingosine kinase type 1 (SPHK1) enzyme activity upon stimulation with both TNF-alpha or IL-1beta. This transient activation of SPHK1 was found to be required for cytokine-induced COX-2 transcription and PGE2 production, since not only specific siRNA (abolishing both basal and induced SPHK1 enzyme activity), but also a dominant-negative SPHK1 mutant (suppressing induced SPHK1 activity only) both reduced COX-2 and PGE2. Furthermore, TNF-alpha- or IL-1beta-induced transcription of selected cytokines, chemokines, and adhesion molecules (IL-6, RANTES, MCP-1, and VCAM-1) was found to require SPHK1 activation. Suppression of SPHK1 activation led to reduction of cytokine-induced IkappaBalpha phosphorylation and consequently diminished NFkappaB activity due to reduced nuclear translocation of RelA (p65), explaining the dependence of inflammatory mediator production on SPHK1 activation. Inhibition of basal SPHK1 activity by N,N-dimethylsphingosine or by downregulation of its expression using siRNA induced spontaneous apoptosis in A549 cells, an effect that can be explained through interference with constitutive NFkappaB activity in this cell type. In contrast, expression of the dominant-negative mutant did not induce apoptosis. Taken together, these findings demonstrate a role of SPHK1 activation in proinflammatory signalling and of SPHK1 basal activity in survival of A549 lung carcinoma cells.


Subtle psychiatric presentations of endocrine diseases.
Endocrine disorders frequently present initially to psychiatrists. This article reviews the differential diagnosis of psychiatric and endocrine disorders. The range of endocrinopathies is presented, with emphasis placed on the common psychiatric symptomatology associated with these conditions. Various signs and symptoms that might stimulate a psychiatrist to pursue a work-up for each endocrine disorder are also emphasized.


Lymph node dissection around the splenic artery and hilum in advanced middle third gastric carcinoma.
To evaluate the clinicopathological factors influencing lymph node metastasis around the splenic artery and hilum and the effect of spleen-preserved lymphadenectomy in advanced middle third gastric carcinoma. We retrospectively studied 131 patients with advanced middle third gastric carcinoma who had received D2 lymphadenectomy and lymph node dissection around the splenic artery and hilum, from 2000 to 2004. Of these patients, 62 simultaneously underwent splenectomy and 69 underwent spleen-preserved lymphadenectomy. The incidences of Nos. 10 and 11 lymph node metastases were 21% and 15%, respectively, in advanced middle third gastric carcinoma. A tumor size larger than 5 cm, metastases of Nos. 1 and 7-9 lymph node were independent risk factors for metastasis of No. 10 and/or No. 11 lymph node. The spleen-preserved group had a slightly better survival rate and a relatively lower rate of postoperative complications than the splenectomy group. No. 10 and/or No. 11 lymph node metastasis was an independent prognostic factor, while splenectomy was not. It is necessary to remove the lymph nodes around the splenic artery and hilum to achieve radical resection in advanced middle third gastric carcinoma patients with risk factors. Our results demonstrate that spleen-preserved lymphadenectomy is a good option for those patients.


Effect of different balance training programs on postural control in chronic ankle instability: a randomized controlled trial.
Chronic ankle instability (CAI) is a common sequence of ankle sprain. Conservative treatment of CAI is currently accepted as a primary mean of managing the condition and preventing of recurrence. The purpose of the current study was to evaluate the effect of Weight-bearing Exercise for Better Balance (WEBB) program and unilateral balance training exercises on postural control in females with CAI. Thirty-five females with CAI participated in this study. The participants' mean values of age, body mass, height, and body mass index were 21.76 ± 1.96 y, 64.82 ± 9.37 kg, 161.85 ± 7.24 cm, and 24.76 ± 3.76 kg/m², respectively. They were randomly assigned into three groups: experimental group A (n = 13) who received WEBB program, experimental group B (n = 12) who received unilateral balance training, and control group C (n = 10) using statistical random tables. Balance parameters were measured for all participants via Biodex Balance System (BBS) before and after four weeks of balance training. They included overall stability index (OASI), antero-posterior stability index (APSI), and medio-lateral stability index (MLSI). There was a significant improvement in the post testing mean values of OASI and APSI, compared with the pre testing values in both experimental groups (A and B). There was no significant difference between the pre and post testing mean values of MLSI in the experimental group (A). Both WEBB program and unilateral balance training have positive effects on postural control in females with CAI.


The role of gene conversion in preserving rearrangement hotspots in the human genome.
Hotspots of non-allelic homologous recombination (NAHR) have a crucial role in creating genetic diversity and are also associated with dozens of genomic disorders. Recent studies suggest that many human NAHR hotspots have been preserved throughout the evolution of primates. NAHR hotspots are likely to remain active as long as the segmental duplications (SDs) promoting NAHR retain sufficient similarity. Here, we propose an evolutionary model of SDs that incorporates the effect of gene conversion and compare it with a null model that assumes SDs evolve independently without gene conversion. The gene conversion model predicts a much longer lifespan of NAHR hotspots compared with the null model. We show that the literature on copy number variants (CNVs) and genomic disorders, and also the results of additional analysis of CNVs, are all more consistent with the gene conversion model.


The effect of prostaglandin E2 on the initial immune response to herpes simplex virus infection.
Numerous clinical situations, demonstrated to be associated with reactivation of herpes simplex virus infections, have also been shown to produce increases in local levels of prostaglandins. The current study was initiated to determine if prostaglandins play a role in the immune response and control of herpes simplex virus infections. Lymphocytes from volunteers were stimulated with concanavalin A, herpes simplex virus 1, or herpes simplex virus 2 in the presence of prostaglandin E2 or ibuprofen, and the lymphocytes served as their own controls. The data suggest a statistically significant suppression in nonspecific T cell mitogen stimulation (concanavalin A), as well as specific herpes simplex virus 1 and 2 stimulations as measured by tritiated thymidine uptake by lymphocytes when stimulated in the presence of prostaglandin E2. Ibuprofen did not alter the proliferative response to concanavalin A, herpes simplex virus 1, or herpes simplex virus 2 stimulation. This report examines the involvement of prostaglandins in herpesvirus infection such as the suppression of T cell function, allowing for a clinical recurrence. The usefulness of nonsteroidal antiinflammatory agents in the therapy of herpes simplex virus infections is also discussed.


Synthesis and electrochemical applications of gold nanoparticles.
This review covers recent advances in synthesis and electrochemical applications of gold nanoparticles (AuNPs). Described approaches include the synthesis of AuNPs via designing and choosing new protecting ligands; and applications in electrochemistry of AuNPs including AuNPs-based bioelectrochemical sensors, such as direct electrochemistry of redox-proteins, genosensors and immunosensors, and AuNPs as enhancing platform for electrocatalysis and electrochemical sensors.


Dataset analysis on Cu9S5 material structure and its electrochemical behavior as anode for sodium-ion batteries.
The data presented in this data article are related to the research article entitled "Facile Synthetic Strategy to Uniform Cu9S5 Embedded into Carbon: A Novel Anode for Sodium-Ion Batteries" (Jing et al., 2018) [1]. The related experiment details of pure Cu9S5 has been stated. The structure data of pure Cu9S5 and the electrochemical performance for sodium-ion batteries are described.


Synthesis of 1,3-distearoyl-2-oleoylglycerol by enzymatic acidolysis in a solvent-free system.
1,3-Distearoyl-2-oleoylglycerol (SOS) is widely used as a cocoa butter improver and an anti-blooming agent in the chocolate industry. In this study, an effective process was developed to prepare SOS by enzymatic acidolysis. Under optimal reaction conditions (substrate molar ratio of 12, NS40086 loading of 10%, a solvent-free system, 75°C for 4h), a SOS yield of 70.2% was obtained. Subsequently, two-step purification was applied to purify the crude SOS product. Free fatty acids were completely removed after molecular distillation. After acetone fractionation, the purity of SOS reached 92.2% with an 85.1% recovery. Comparison of various physicochemical properties of purified SOS and a commercial cocoa butter improver showed their properties to be similar. This study provides an effective and sustainable process for the synthesis of SOS product, which is expected to be used as a high-quality cocoa butter improver or an anti-blooming agent in the chocolate industry.


Oral cancer and herpes simplex virus--a review.
Numerous studies have suggested that patients with oral cancer have an increased immune response to herpes simplex virus. However, the number of cases has always been small, and essential controls have not always been included. Laboratory experiments have shown that herpes simplex virus can be carcinogenic or cocarcinogenic under certain circumstances and so must be considered as a possible etiologic agent in oral cancer. This article reviews past research and suggests priorities for future investigations.


Identification of Tcf-4 as a transcriptional target of p53 signalling.
T-cell factor (Tcf)-4 is a main transcription factor to pass on Wnt/beta-catenin signalling. The tumour suppressor protein p53 contributes as a transcription factor to cell-cycle arrest and apoptosis induction. Mutations of components in p53 and Wnt/beta-catenin signalling networks play a part in tumour formation. Here, we identify the Tcf-4 gene as a downstream effector of p53. Induction of wild-type p53 in a tet-off regulated human colon cell system leads to the reduction of Tcf-4 mRNA and protein levels. Also, mRNA of the Tcf-4 target gene uPAR is downregulated after p53 induction. Expression of a luciferase reporter controlled by the Tcf-4 promoter is repressed by wild-type p53, but not by a p53 mutant deficient in DNA binding. Such a regulation is seen in cell lines of different origin. These findings directly link Wnt/beta-catenin signalling and p53 tumour suppressor function and may provide a mechanism by which loss of p53 function contributes to progression in the adenoma/carcinoma sequence in colon tumours. Furthermore, since Tcf-4 is expressed in many tissues and downregulation of Tcf-4 by p53 is seen in several different cell types, this regulation likely plays a role in proliferation control of all tissues that can express p53 and Tcf-4.


A case of hypertrophic obstructive cardiomyopathy and acquired von Willebrand syndrome: response to medical therapy.
Heyde's syndrome is the combined occurrence of acquired von Willebrand disease caused by aortic valve stenosis and gastrointestinal bleeding that occurs particularly in elderly patients. The bleeding may be linked to the intravascular shear-induced proteolysis of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). Hypertrophic obstructive cardiomyopathy (HOCM) in the left ventricular outflow tract generates a high shear stress condition that can induce such proteolysis. We report the case of a 70-year-old woman with HOCM who had severe anemia and loss of HMWMs. After reduction of the outflow gradient by medical treatment, vWF normalized, and her anemia alleviated.


Serum NT-proBNP level for predicting functional outcomes after acute ischemic stroke.
N-terminus pro-brain natriuretic peptide (NT-proBNP) has been studied and recognized as a biomarker of cardiac thrombogenicity and stroke risk. However, the association between NT-proBNP and functional outcomes following acute ischemic stroke is still debated. This study aimed to investigate whether serum NT-proBNP level is associated with functional outcomes in acute ischemic stroke individuals. This prospective cohort study included patients diagnosed with acute ischemic stroke, and serum NT-proBNP levels were measured within 72 h. At 3 months, all patients were followed up for a modified Rankin Scale (mRS), and logistic regression models were used to evaluate the association of NT-proBNP on the primary outcome, in which a score of 3-6 was classified as an unfavorable functional outcome. Sixty-seven patients were enrolled in the study, and 23 (34.3%) patients were identified with an unfavorable functional outcome. Elevated serum NT-proBNP levels (> 100 pg/mL) were observed in 57 (85.1%) patients, and the Youden index demonstrated a cutpoint estimation of poor outcomes at 476 pg/mL with 74% sensitivity and 63% specificity. Multivariate regression analysis showed an elevation of NT-proBNP above the cutpoint level was an independent predictor for unfavorable functional outcomes, odds ratio 3.77, 95% confidence interval (1.04-13.62), P = 0.04. The present study demonstrated that elevated serum NT-proBNP levels were expected among acute ischemic stroke patients and represented the risk of unfavorable functional outcomes, suggesting that NT-proBNP might be a useful biomarker for predicting prognosis after ischemic stroke.


The effect of transpyloric enteral nutrition on inflammatory response and prognosis for patients with Corona Virus Disease-19 in intensive care unit: A STROBE compliant study.
To investigate the effect of transpyloric enteral nutrition (TEN) on NLRP1, inflammatory response and prognosis for patients with Corona Virus Disease-19 (COVID-19) in intensive care unit (ICU). The present prospective observational study included 29 cases of COVID-19 patients in ICU who admitted to our hospital during February 2020 to March 2020. All the patients were divided into gastrogavage groups (n = 16) and TEN group (n = 13) according to route of enteral nutrition. Serum levels of C-reactive protein (CRP), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and NLRP1 (NLR family pyrin domain containing 1) was detected by enzyme linked immunosorbent assay (ELISA). Serum levels of lymphocyte, albumin and hemoglobin was detected using an automatic biochemical analyzer. Patients' demographic and clinical characteristics were collected and analyzed. Kaplan-Meier (K-M) curve was conducted for survival analysis and receiver operating characteristic curve was used for the analysis of diagnostic value of biomarkers. All the patients were followed-up for 3 months. This study found that the survival group had higher rate of TEN therapies than the deceased. COVID-19 patients in ICU on TEN had lower APACHE II scores, frequency of feeding suspension and mortality, however, with higher content of albumin was found at 5th day. The incidence of nutritional intolerance including abdominal distension and gastric retention in patients on TEN was notably lower than those on gastrogavage. The serum levels of NLRP1, CRP, IL-1β, IL-6 and TNF-α decreased in a time-dependent manner, but patients on TEN had lower levels of NLRP1, CRP and IL-1β than patients on gastrogavage. A positive correlation was found among NLRP1 and inflammatory factors, and COVID-19 patients with lower NLRP1 had longer survival time. Serum NLRP1 also exhibited diagnostic value for the death of COVID-19 patients. TEN decreased inflammatory response and improved the prognosis for COVID-19 patients in ICU.


Moisture as a factor influencing the distributions of two species of terrestrial salamanders.
Plethodon richmondi shenandoah occurs in at least three geographically isolated talus slopes in Shenandoah National Park, Virginia, U.S.A., each surrounded by a continuous population of Plethodon c. cinereus in the soil outside the talus. Distributions are contiguous but largely non-overlapping. The talus presents a much drier habitat than does the surrounding soil. Four experiments were designed to test the responses of the two species to moisture and substrate. Although shenandoah lives in a habitat generally drier than that of cinereus, both species choose the wet end of a moisture gradient and do not differ significantly in moisture preference. When given choices between a substrate of rock or soil, the two species respond similarly: neither expresses a preference when both substrates are moist and both choose soil over rock as the substrates dry, showing that substrate preference is based on moisture content and not texture. A third experiment demonstrates that cinereus suffers significantly greater mortality and loss of body water when subjected to a drying rock substrate than when subjected to a soil substrate, since the latter holds moisture longer. Thus the talus most likely presents a greater stress of dehydration to salamanders than does the soil. A fourth experiment shows that when forced to dehydrate, shenandoah survives longer, loses significantly less body water per hour, and withstands a greater loss of body water before death than does cinereus.The conclusions drawn are that cinereus inhabits areas of deep soil not due to a preference for that substrate but due to the requirement of a moist substrate, and it cannot enter the talus due to the dry conditions there. P. r. shenandoah, on the other hand, neither prefers the rocky nor the dry conditions of the talus and is probably excluded from the soil by the presence of cinereus. The survival of shenandoah in the talus is due, at least in part, to its ability to withstand the stress of dehydration for a longer period than can cinereus.


Spliced leader RNA trans-splicing discovered in copepods.
Copepods are one of the most abundant metazoans in the marine ecosystem, constituting a critical link in aquatic food webs and contributing significantly to the global carbon budget, yet molecular mechanisms of their gene expression are not well understood. Here we report the detection of spliced leader (SL) trans-splicing in calanoid copepods. We have examined nine species of wild-caught copepods from Jiaozhou Bay, China that represent the major families of the calanoids. All these species contained a common 46-nt SL (CopepodSL). We further determined the size of CopepodSL precursor RNA (slRNA; 108-158 nt) through genomic analysis and 3'-RACE technique, which was confirmed by RNA blot analysis. Structure modeling showed that the copepod slRNA folded into typical slRNA secondary structures. Using a CopepodSL-based primer set, we selectively enriched and sequenced copepod full-length cDNAs, which led to the characterization of copepod transcripts and the cataloging of the complete set of 79 eukaryotic cytoplasmic ribosomal proteins (cRPs) for a single copepod species. We uncovered the SL trans-splicing in copepod natural populations, and demonstrated that CopepodSL was a sensitive and specific tool for copepod transcriptomic studies at both the individual and population levels and that it would be useful for metatranscriptomic analysis of copepods.


Sonoelectrochemical activation of peroxymonosulfate: Influencing factors and mechanism of FA degradation, and application on landfill leachate treatment.
In this work, sonoelectrochemically activated peroxymonosulfate (US-EC/PMS) was used to degrade fulvic acid (FA) in water. Compared with other technologies, the US-EC/PMS system can achieve higher FA decolorization in a short time. Moreover, the benefits of synergy are more prominent in the US-EC/PMS system. The effects of operating parameters on the sonoelectrochemical degradation of FA were investigated, including initial pH, initial FA concentration, current density, ultrasonic power, PMS dosage. The results showed the initial FA concentration and current density were critical to the degradation of FA. Under optimized parameters: initial pH of 2, 50 mg L-1 initial FA concentration, 30 mA cm-2 current density, 50 W ultrasonic power, 1 mM PMS dosage, the US-EC/PMS system can achieve 93% FA decolorization. The calculation results of current efficiency and energy consumption indicate that the introduction of PMS into the US-EC system has economic applicability. Scavenger experiments and electron paramagnetic resonance suggest that hydroxyl radicals, sulfate radicals, and singlet oxygen were the main ROS produced in the US-EC/PMS system. Accordingly, the possible mechanism of FA degradation by sonoelectrochemical activation PMS was proposed. Finally, the US-EC/PMS system was used to treat the aged landfill leachate. Three-dimensional fluorescence analysis showed that most of the humic substances (Hss) were effectively removed, and the biodegradability of the leachate was considerably improved. In addition, the effective removal of COD, chroma, and ammonia nitrogen were observed, proving that this technology is a powerful means to treat organic wastewater contaminated by Hss.


Role of AKR1B10 and AKR1B8 in the pathogenesis of non-alcoholic steatohepatitis (NASH) in mouse.
Non-alcoholic steatohepatitis (NASH) is a clinically important spectrum of non-alcoholic fatty liver disease (NAFLD) in humans. NASH is a stage of NAFLD progression wherein liver steatosis accompanies inflammation and pro-fibrotic events. Presently, there are no approved drugs for NASH, which has become a leading cause of liver transplant worldwide. To discover novel drug targets for NASH, we analyzed a human transcriptomic NASH dataset and found Aldo-keto reductase family 1 member B10 (AKR1B10) as a significantly upregulated gene in livers of human NASH patients. Similarly murine Akr1b10 and Aldo-keto reductase family 1 member B8 (Akr1b8) gene, which is a murine ortholog of human AKR1B10, were also found to be upregulated in a mouse model of diet-induced NASH. Furthermore, pharmacological inhibitors of AKR1B10 significantly reduced the pathological features of NASH such as steatosis, inflammation and fibrosis in mouse. In addition, genetic silencing of both mouse Akr1b10 and Akr1b8 significantly reduced the expression of proinflammatory cytokines from hepatocytes. These results, thus, underscore the involvement of murine AKR1B10 and AKR1B8 in the pathogenesis of murine NASH and raise an intriguing possibility of a similar role of AKR1B10 in human NASH.


[A double-blind dose ranging study of weekly subcutaneous administration of rHuEPO (KRN5702) on post-phlebotomy anemia of patients scheduled for predeposit autologous blood transfusion (multicenter late PhII study)].
Preoperative blood reservation for autologous blood transfusion generally causes anemia. We performed a double blind controlled study to determine the optimal dose of subcutaneous rHuEPO (recombinant human erythropoietin, KRN5702) for preventing preoperative anemia due to blood reservation. Patients received KRN5702 subcutaneously once a week in a doses of 12000, 24000 or 36000 IU by a double blind technique. After storage of 1200 ml of their own blood right before surgery, their hemoglobin (Hb) averaged about 1 and was about 0.5 g/dl lower than the level before administration of KRN5702 in doses of 12000 and 24000 IU, respectively. This fall was significant. In patients receiving KRN5702 in a dose of 36000 IU, the level of Hb rose instead of a fall; Hb immediately before surgery was 1.1% higher than that before administration which, however, was not significant. This elevation indicates a possibility of abnormal elevation of Hb at this dose. The mean Hb value right before surgery was significantly lower in patients receiving 12000 IU KRN5702 than in patients of the other two groups. The recovery rate of Hb was an indicator to reflect improvement of anemic conditions, and increased as the dose increased after the blood reservation. The rate in the 12000 IU group was significantly lower than that in the other two groups; there was not much difference between the other two rates. We estimated that to reserve 1200 ml of autologous blood, 24000 IU of KRN5702 is adequate but not excessive. One patient receiving 24000 IU showed side effects including an elevation of body temperature, rash, and edema.


Resonant thermal energy transfer to magnons in a ferromagnetic nanolayer.
Energy harvesting is a concept which makes dissipated heat useful by transferring thermal energy to other excitations. Most of the existing principles are realized in systems which are heated continuously. We present the concept of high-frequency energy harvesting where the dissipated heat in a sample excites resonant magnons in a thin ferromagnetic metal layer. The sample is excited by femtosecond laser pulses with a repetition rate of 10 GHz, which results in temperature modulation at the same frequency with amplitude ~0.1 K. The alternating temperature excites magnons in the ferromagnetic nanolayer which are detected by measuring the net magnetization precession. When the magnon frequency is brought onto resonance with the optical excitation, a 12-fold increase of the amplitude of precession indicates efficient resonant heat transfer from the lattice to coherent magnons. The demonstrated principle may be used for energy harvesting in various nanodevices operating at GHz and sub-THz frequency ranges.


Smooth pursuit and saccadic eye movements and Wisconsin Card Sorting Test performance in obsessive-compulsive disorder.
Smooth pursuit eye movements (SPEMs), voluntary saccadic eye movements (VSEMs), and neuropsychological test (Touluse-Pieron Test and Wisconsin Card Sorting Test) performance were studied in 23 patients with obsessive-compulsive disorder and 27 age-matched normal control subjects. The patients performed more poorly than the control subjects on the SPEM and, to a lesser degree, VSEM measures. They also showed impairment on some aspects of the neuropsychological tests. No relationship was found between eye movement performance and neuropsychological impairment.


DNA repair gets physical: mapping an XPA-binding site on ERCC1.
Two recent reports provide new physical information on how the XPA protein recruits the ERCC1-XPF heterodimer to the site of damage during the process of mammalian nucleotide excision repair (NER). Using chemical shift perturbation NMR experiments, the contact sites between a central fragment of ERCC1 and an XPA fragment have been mapped. While both studies agree with regard to the XPA-binding site, they differ on whether the ERCC1-XPA complex can simultaneously bind DNA. These studies have important implications for both the molecular process and the design of potential inhibitors of NER.


Screening and treating problematic substance use among patients in psychiatry - obstacles and solutions.
In Sweden, national guidelines recommend that all staff in the healthcare system systematically screen patients for alcohol use and illicit substance use. Where hazardous use is identified, it should be addressed as soon as possible, preferably through brief interventions (BI). Results from a previous national survey showed that most clinic directors stated that they had clear guidelines for screening alcohol use and illicit substance use, but that fewer staff than expected used screening in their work. This study aims to identify obstacles and solutions to screening and brief intervention, based on survey respondents' free-text responses to open-ended questions. A qualitative content analysis yielded four codes: guidelines, continuing education, cooperation and resources. The codes indicated that staff would need (a) clearer routines in order to optimize compliance with the national guidelines; (b) more knowledge about how to treat patients with problematic substance use; (c) better cooperation between addiction care and psychiatry; and (d) increased resources to improve routines at their own clinic. We conclude that increased resources could contribute to better routines and cooperation, and provide increased opportunities for continuing education. This could increase guideline compliance and increase healthy behavior changes among patients in psychiatry with problematic substance use.


Diagnostic value of salivary cortisol in the CRH stimulation test in premature infants.
According to a recent nationwide survey in Japan, a significant proportion of very low birth weight infants (VLBWI) develop late-onset circulatory collapse after the first week of life. Small doses of glucocorticoid are very effective in these patients, and relative adrenal insufficiency is suspected to be the main cause of the condition. Although the CRH test is required to evaluate the hypothalamic-pituitary-adrenal axis, obtaining multiple blood samples is invasive. The present study was carried out to validate the consistency of the cortisol profiles of matched serum and saliva samples collected as part of the CRH test from VLBWI. In 23 VLBWI with a gestational age of less than 29 wk, we performed CRH tests at 2 wk after birth and at term. Their cortisol values were measured at the baseline and 30 min after the administration of a single dose of human CRH (1 μg/kg) using matched serum and saliva samples. In 26 CRH tests in 19 infants, we were able to measure both serum and salivary cortisol. Significant correlations were detected between the infants' serum and salivary cortisol values (r=0.78; P<0.0001), the increases in these values induced in response to the CRH test (r=0.81; P<0.0001), and their peak serum and salivary cortisol values (r=0.68; P=0.0001). This study indicated that using salivary cortisol measurements for the CRH test could be a reliable method for evaluating the hypothalamic-pituitary-adrenal axis in VLBWI with gestational age of less than 29 wk.


Association between genetic polymorphisms of beta2 adrenergic receptors and nocturnal asthma in Egyptian children.
Identification of the genetic basis of asthma may contribute to the discovery of effective asthma drugs. Our aim was to estimate the association between B2 adrenergic receptor (ADRB2) polymorphisms and nocturnal asthma in Egyptian children. ADRB2 polymorphisms Gly16 and Glu27 were genotyped in 200 Egyptian children (90 with nocturnal asthma and 110 healthy controls) using allele-specific polymerase chain reaction. The homozygous (Gly16) genotype significantly increased the risk of nocturnal asthma (odds ratio [OR], 3.2; 95% CI, 1.3-7.7; P = .003), as did the Gly allele (OR, 1.8: 95% CI, 1.2-2.8). Our study demonstrated that nocturnal asthma was associated with ADRB2 Arg/Gly polymorphisms but not with ADRB2 Gln/Glu polymorphisms.


Isolation of two antifungal compounds fromNeolitsea cuipala and their activity against some plant pathogenic fungi.
Zeylanidine and zeylanicine isolated fromNeolitsea cuipala fruit peels are found to be potential antifungal agents againstHelminthosporium oryzae, Fusarium oxysporum, Alternaria solani, Curvularia varuciformis andColletotrichum gleosporioides.


Characterization of CK2 holoenzyme variants with regard to crystallization.
A search for strategies was conducted in order to obtain a human protein kinase CK2 preparation which would be suitable for crystallization, despite the fact that the recombinant enzyme is abundant and can be readily purified to homogeneity. This seemingly contradiction is based on the fact that the catalytic subunit moiety of the human CK2 holoenzyme is not stable neither as a free subunit nor in the tetrameric complex. All attempts to prevent degradation failed. Hence, alternative approaches were designed in order to avoid this degradation, which was expected to hamper any crystallization efforts severely. One of the approaches chosen was the production of a chimeric holoenzyme made up from a human regulatory subunit and a catalytic subunit from Z. mays. The plant catalytic subunit, in contrast to the human counterpart is very stable and does not undergo this kind of degradation. The second strategy to tackle the problem of instability was to produce the homologous recombinant human CK2 holoenzyme and then, instead of trying to avoid degradation, attempt to accelerate degradation until all catalytic subunit material was converted to the degraded form, i.e. a 40 kDa polypeptide.


Docking studies and anti-inflammatory activity of beta-hydroxy-beta-arylpropanoic acids.
The article describes a two-step synthesis of diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylyl)butanoic acids. In the first step an intermediate alpha-bromo propanoic acid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatsky reaction in presence of Zn in tetrahydrofuran (THF) at -5 to 10 degrees C between the previously synthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied beta-hydroxy-beta-arylpropanoic acids has already been reported. These beta-hydroxy-beta-arylpropanoic acids belong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDs such as ibuprofen. The anti-inflammatory activity and gastric tolerability of the synthesized compounds were evaluated. Molecular docking experiments were carried out to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl-alkanoic acids class. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration and that the compounds 2-(9-(9-hydroxy-fluorenyl))-2-methylpropanoic acid (5) and 3-hydroxy-3,3-diphenyl-propanoic acid (3) possess the strongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID,and that none of tested substances or ibuprofen produced any significant gastric lesions.


Arterial occlusion due to Listeria meningoencephalitis in an immunocompromised boy.
Sequential CAT scan studies of the brain were performed in a 7-year-old boy with Listeria monocytogenes serotype 1 meningoencephalitis. The infection occurred while he was receiving maintenance chemotherapy for T-cell non-Hodgkin lymphoma. A lesion in the right hemisphere during the infection resulted in an excessive enlargement of the right ventricle 10 months later, most probably caused by arterial occlusion.


Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory.
The aim of this study was to investigate the association between epilepsy and perinatal brain injury in a cohort of 610 infants born preterm at <33 weeks' gestation. The prevalence of epilepsy in this cohort was 4.3% as determined by a postal questionnaire survey. Most children with epilepsy (16 of 24) had high-risk cranial ultrasound lesions including haemorrhagic parenchymal infarction (HPI), posthaemorrhagic hydrocephalus, and cystic periventricular leukomalacia (PVL). Of all the children in our cohort with high-risk brain lesions, those with epilepsy were more likely to have HPI and significantly less likely to have cystic PVL, although it is possible that PVL was not noticed in some cases. Children with epilepsy and high-risk cranial ultrasound lesions also showed more cognitive impairment than children with high-risk lesions but no epilepsy, which suggested more cortical grey-matter damage. We suggest that brain injury has occurred outside the confines of the periventricular white matter in this group of preterm infants with epilepsy.


Unexpected formal insertion of CO2 into the C-Si bonds of a zinc compound.
Reaction of [κ2-PR2C(SiMe3)Py]2Zn (R = Ph, 2a; iPr, 2b) with CO2 affords the products of formal insertion at the C–Si bond, [κ2-PR2CC(O)O(SiMe3)Py]2Zn (R = Ph, 3a; iPr, 3b). Insertion product 3b was structurally characterized. The reaction appears to be a stepwise insertion and rearrangement of CO2 based on kinetic data.


Legislation contagion: the spread of problematic new HIV laws in Western Africa.
Model legislation can be a useful tool for fighting HIV/AIDS, but only if it is based on sound human rights principles. In 2004, AWARE-HIV/AIDS prepared a model law on HIV for use in Western Africa. Several countries in the region have already drafted national laws based on the model law. In this article, Richard Pearshouse reviews some of the key provisions in the model law, identifying a number of human rights concerns that should be addressed before such legislation should be considered as a model to be implemented by national legislatures.


Visual field defects after uneventful vitrectomy for epiretinal membrane with indocyanine green-assisted internal limiting membrane peeling.
To report visual field defects after vitrectomy for epiretinal membrane with indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling. Interventional consecutive case series. A retrospective review of 16 eyes of 16 patients who underwent vitrectomy for idiopathic epiretinal membrane. Indocyanine green-assisted ILM peeling was performed in 7 of 16 eyes. The main outcome measure was postoperative visual field. Four of seven eyes (57%) with ICG-assisted ILM peeling had visual field defects postoperatively. The field defects identified were nasal in three eyes; in the fourth eye, the visual field was constricted to approximately 30 degrees. None of the nine eyes without ICG-assisted ILM peeling had a visual field defect. Peripheral visual field defects may occur after vitrectomy with ICG-assisted ILM peeling. Although the cause of the defects is unclear, the potential role of ICG toxicity requires further investigation.


The effects of amiloride, ouabain and osmolality on sodium transport across bovine cornea.
Electrical parameters across different parts of bovine cornea were measured after varying osmolality, temperature, pH and sodium concentration of bathing solutions, with and without amiloride or ouabain. It is concluded, that the transcorneal potential difference represents the sum of the transendothelial and transepithelial potential differences. Amiloride completely and reversibly inhibited the potential difference and the short circuit current originating in the epithelium (Ki = 2 X 10(-6) mol/l). Furthermore, the transcorneal electrical resistance increased by 28 +/- 8%. The results were used to calculate the cellular and paracellular pathway resistances in the corneal epithelium. An equivalent electrical circuit for sodium transport across the bovine cornea is proposed, which simulates the results obtained.


IFN-tau: a novel subtype I IFN1. Structural characteristics, non-ubiquitous expression, structure-function relationships, a pregnancy hormonal embryonic signal and cross-species therapeutic potentialities.
IFN-tau (IFN-tau) constitutes a new class of type I IFN which is not virus-inducible, unlike IFN-alpha and IFN-beta, but is constitutively produced by the trophectoderm of the ruminant conceptus during a very short period in early pregnancy. It plays a pivotal role in the mechanisms of maternal recognition of pregnancy in ruminants and it displays high antiviral and antiproliferative activities across species with a prominent lack of cytotoxicity at high concentrations in vitro in cell culture and possibly in vivo. It exhibits high antiretroviral activity against HIV and exhibits immunosuppressive activity in a multiple sclerosis model and reduces embryo and fetal mortality by stimulation of IL-10 production. In this review all the biochemical and para-hormonal properties of this novel IFN-tau are described in detail: structural characteristics of proteins and genes, trophoblast expression, regulation of its expression, structure of its gene promoter, its absence in human species and in non-ruminant animals, the evolution of the IFN-tau genes, its structure-function relationships with its three-dimensional structure, structural localization of biological activities, its lack of cytotoxicity and its receptor. Surprisingly, for an IFN, IFN-tau is also a pregnancy-embryonic signal with paracrine antiluteolytic activity. In order to maintain luteal progesterone secretion, IFN-tau inhibits PGF-2alpha pulsatile secretion and oxytocin uterine receptivity in early pregnancy. It is believed to suppress pulsatile release of endometrial PGF-2alpha by preventing oxytocin and estrogen receptor expression. Additionally, it directly regulates prostaglandin metabolism and possibly the PGE:PGF-2alpha ratio.