Diagnostic Evaluation of Upper Extremity Masses and Tumors.
The appropriate evaluation of hand and upper extremity masses is an important aspect of the care of orthopedic patients. Although most of these masses are benign, the orthopedic surgeon must have a high index of suspicion when assessing them because early diagnosis and treatment of aggressive or malignant masses may have a great effect on patient outcomes. This article provides an overview of benign and malignant osseous and soft tissue masses that orthopedic surgeons may encounter and a detailed algorithm for evaluating these masses. [Orthopedics. 2017; 40(5):e758-e764.].


Both protein kinase C and calcium mediate activation of the Na+/H+ antiporter in Chinese hamster embryo fibroblasts.
Chinese hamster embryo fibroblast cells (CHEF/18) possess a plasma membrane-associated, amiloride-sensitive Na+/H+ antiporter that affects intracellular pH (pHi) and is activated by growth factor addition. Our results using 14C-benzoic acid distribution indicate that both epidermal growth factor (EGF) and thrombin are capable of causing rapid rises in the pHi of CHEF/18 cells. The maximal shift induced by these factors is 0.20 to 0.25 pH units above the basal unstimulated level. Distinctive differences were observed between the modes of action of these two growth factors. Sequential additions revealed that the rise in pHi due to EGF was additive with that caused by diacylglycerols (DAG), while that of thrombin was not. Furthermore, exposure of cells to the phorbol ester PMA for a prolonged period of time in order to down-regulate protein kinase C (pkC), or treatment with the pkC inhibitor H-7, abolished the pHi response to thrombin but not to EGF. In contrast, incubation of cells in nominally calcium-free medium or with the calmodulin antagonists W-7 or trifluoperazine (TFP) decreased only the ability of EGF to cause changes in pHi. These data suggest that there are two distinct mechanisms for activation of the Na+/H+ antiporter in CHEF/18 fibroblast cells and thus provide an example of the use of alternative modes for the modulation of intracellular processes.


Evaluation of the ceramic liner bonding effect between zirconia and lithium disilicate.
Little information is available for the strength of bonding between zirconia and lithium disilicate as affected by surface pretreatment methods. The purpose of this in vitro study was to investigate the shear bond strength (SBS) between zirconia core and lithium disilicate (LS2) veneered ceramic after surface pretreatments. Fully sintered yttrium oxide partially stabilized tetragonal zirconia (Y-TZP) disk specimens were fabricated from zirconia ceramic materials. Specimens were divided into 4 groups with surface pretreatments applied (the as-received group, the liner group, the airborne-particle abrasion group, and the airborne-particle abrasion-plus-liner group). After pressing LS2 on a zirconia disk, shear force was applied perpendicular to the zirconia-LS2 interface. Data were analyzed using 2-way ANOVA and Tukey test (α=.05). For each group, the failure modes were measured by using optical microscopy, scanning electron microscopy, energy dispersive x-ray spectroscopy, and x-ray diffraction. Airborne-particle abrasion induced significantly lower interfacial strength between zirconia and lithium disilicate (P<.05). After airborne-particle abrasion of the surface, the increased monoclinic volume fraction and reduced coefficient of thermal expansion of zirconia may weaken the interfacial strength between zirconia and LS2. The liner treatment significantly improved the adhesion between zirconia core and veneering LS2 (P<.05). The SBS values decreased in the following order: liner group > airborne-particle abrasion-plus-liner group > airborne-particle abrasion group. The interfacial image of zirconia and LS2 showed a fusion of crystal structure between the 2 materials. Some components of the silica-containing glass-ceramic liner led to an increase in SBS as diffusion occurred on the zirconia surface. The bond strength between zirconia and veneering LS2 was significantly increased by application of silica-containing glass-ceramic liner but was decreased with airborne-particle abrasion.


Delta13CO2 excretion and expression of dyspeptic symptoms in patients evaluated for Helicobacter pylori infection by [13C] urea breath test.
Previous studies showed that either the urease activity possessed by H. pylori and the bacterial load may influence the results of the [13C] urea breath test. However, the correlation between urease activity and dyspepsia is unclear. The aim of our study was to evaluate whether the urease activity of the gastroduodenal tract may influence the severity of dyspeptic symptoms. In all, 2520 dyspeptic patients (1109 men, 1411 women; mean age 47 +/- 16 years) without gastroesophageal reflux disease, diabetes, vascular disorders, liver and biliary tract diseases, and tumors of the gastrointestinal tract and with a normal appearing abdominal ultrasonography were enrolled. All these patients underwent a [13C] urea breath test and filled out a questionnaire on dyspeptic symptoms. Subjects were divided in five different groups according to delta over baseline (DOB) values (group 1 < 3.5, group 2 = 3.5-6; group 3 = 6.1-11, group 4 = 11.1-23, group 5 > 23.1). The prevalence and intensity of dyspeptic symptoms were compared among groups. In all, 1688 patients (67%, 928 females and 760 males; mean age 48 +/- 15 years) were H. pylori-positive. The chi-squared test and analysis of variance showed increase of frequency and intensity of each dyspeptic symptom according to DOB values. In conclusion, Dyspepsia may parallel gastric urease activity. However, whether higher DOB values are related to higher bacterial load or, alternatively, to the presence of particular H. pylori strains able to produce larger amounts of urease is uncertain.


In vitro study of genes and molecular pathways differentially regulated by synchrotron microbeam radiotherapy.
The aim of this study was to identify genes and molecular pathways differentially regulated by synchrotron-generated microbeam radiotherapy (MRT) versus conventional broadbeam radiotherapy (CRT) in vitro using cultured EMT6.5 cells. We hypothesized (based on previous findings) that gene expression and molecular pathway changes after MRT are different from those seen after CRT. We found that at 24 h postirradiation, MRT exerts a broader regulatory effect on multiple pathways than CRT. MRT regulated those pathways involved in gene transcription, translation initiation, macromolecule metabolism, oxidoreductase activity and signaling transduction in a different manner compared to CRT. We also found that MRT/CRT alone, or when combined with inflammatory factor lipopolysaccharide, upregulated expression of Ccl2, Ccl5 or Csf2, which are involved in host immune cell recruitment. Our findings demonstrated differences in the molecular pathway for MRT versus CRT in the cultured tumor cells, and were consistent with the idea that radiation plays a role in recruiting tumor-associated immune cells to the tumor. Our results also suggest that a combination of MRT/CRT with a treatment targeting CCL2 or CSF2 could repress the tumor-associated immune cell recruitment, delay tumor growth and/or metastasis and yield better tumor control than radiation alone.


Embryo implantation and embryonic stem cell development in primates.
The endocrine dialogue that results in implantation and the successful establishment of pregnancy in primates relies on embryonic secretion of chorionic gonadotrophin (CG). This hormone is a signal of embryo viability and capacity to support the corpus luteum. The expression of CG is apparently restricted to primates. Active or passive immunization of marmoset monkeys against the beta subunit of CG prevented implantation and early pregnancy, without disrupting the ovarian cycle. Studies of individual embryos cultured in vitro showed that CG is secreted at low levels by the blastocyst from before attachment, with secretion increasing exponentially after attachment. Gonadotrophin releasing hormone (GnRH) was also secreted, from mid-blastocyst stages, before the detection of CG. The secretion of GnRH by the embryo continued through the attachment and outgrowth stages of embryonic differentiation in vitro. The hypothetical role of GnRH in regulating CG release during implantation was tested in recently completed experiments. Individual embryos cultured with GnRH, or with agonist or antagonist to GnRH, showed significant variations in their secretion of CG and in their survival in culture, suggesting a causal relationship between these hormones. Embryos cultured with natural GnRH showed enhanced growth and development. Embryonic stem cells, from the inner cell mass of marmoset and rhesus monkeys, were the first primate embryonic stem cells to be isolated and characterized, enabling the subsequent isolation of human embryonic stem cells.


Concept analysis of symptom disclosure in the context of cancer.
Although symptoms suggestive of cancer are the most common reason that people seek healthcare, the process undertaken to disclose the symptoms is unclear. The purpose of this article is to critically analyze the concept of symptom disclosure in the context of cancer. Rodgers' evolutionary approach was applied to analyze the concept of symptom disclosure. Concept analysis indicates that symptom disclosure is a decision-making process in which a person chooses to tell significant others and a healthcare provider about self-identified symptoms. Characteristics of the concept include symptom interpretation, weighing the risks and benefits of disclosure, and taking action. Influencing factors are knowledge, cancer risk perception, personal or family history of cancer, socioeconomic and cultural factors, and access to care. The concept analysis of symptom disclosure provides guidance for developing strategies to promote healthcare-seeking behavior in practice and suggest areas for future research.


Machine-Learning-Based Tool to Predict Target Prostate Biopsy Outcomes: An Internal Validation Study.
The aim of this study is to present a personalized predictive model (PPM) with a machine learning (ML) system that is able to identify and classify patients with suspected prostate cancer (PCa) following mpMRI. We extracted all the patients who underwent fusion biopsy (FB) from March 2014 to December 2019, while patients from August 2020 to April 2021 were included as a validation set. The proposed system was based on the following four ML methods: a fuzzy inference system (FIS), the support vector machine (SVM), k-nearest neighbors (KNN), and self-organizing maps (SOMs). Then, a system based on fuzzy logic (FL) + SVM was compared with logistic regression (LR) and standard diagnostic tools. A total of 1448 patients were included in the training set, while 181 patients were included in the validation set. The area under the curve (AUC) of the proposed FIS + SVM model was comparable with the LR model but outperformed the other diagnostic tools. The FIS + SVM model demonstrated the best performance, in terms of negative predictive value (NPV), on the training set (78.5%); moreover, it outperformed the LR in terms of specificity (92.1% vs. 83%). Considering the validation set, our model outperformed the other methods in terms of NPV (60.7%), sensitivity (90.8%), and accuracy (69.1%). In conclusion, we successfully developed and validated a PPM tool using the FIS + SVM model to calculate the probability of PCa prior to a prostate FB, avoiding useless ones in 15% of the cases.


Dyes Used in Processed Meat Products in the Polish Market, and Their Possible Risks and Benefits for Consumer Health.
Manufacturers are obliged to label processed meat products with information concerning the additives used and nutritional values. The aim of the study was to identify the dyes most frequently used in processed meat, evaluate their influence on specific food qualities, assess whether their use was correct and review their effect on health. The analysis was based on information on the labels and images of processed meat, and used a generalised linear model with a binary dependent variable. The risks and benefits for human health were defined based on the available literature. Twelve dyes were found to be used in the manufacture of processed meat. Carmine was found in 183 of 273 (67.03%) evaluated assortments containing dyes. The occurrence of water, flavourings and high fat and carbohydrate contents increased the chances that a dye would be present in a particular product. Unauthorised use of food additives was found in 20 products, with smoked meat products demonstrating the highest number of non-compliances. In general, the dyes used with food are considered safe; however, reservations are associated with the use of E150C and E150D caramels due to their potential carcinogenic effect, and carmine and annatto due to their allergic effects.


How ionic are room-temperature ionic liquids? An indicator of the physicochemical properties.
Room-temperature ionic liquids (RTILs) are liquids consisting entirely of ions, and their important properties, e.g., negligible vapor pressure, are considered to result from the ionic nature. However, we do not know how ionic the RTILs are. The ionic nature of the RTILs is defined in this study as the molar conductivity ratio (Lambda(imp)/Lambda(NMR)), calculated from the molar conductivity measured by the electrochemical impedance method (Lambda(imp)) and that estimated by use of pulse-field-gradient spin-echo NMR ionic self-diffusion coefficients and the Nernst-Einstein relation (Lambda(NMR)). This ratio is compared with solvatochromic polarity scales: anionic donor ability (Lewis basicity), E(T)(30), hydrogen bond donor acidity (alpha), and dipolarity/polarizability (pi), as well as NMR chemical shifts. The Lambda(imp)/Lambda(NMR) well illustrates the degree of cation-anion aggregation in the RTILs at equilibrium, which can be explained by the effects of anionic donor and cationic acceptor abilities for the RTILs having different anionic and cationic backbone structures with fixed counterparts, and by the inductive and dispersive forces for the various alkyl chain lengths in the cations. As a measure of the electrostatic interaction of the RTILs, the effective ionic concentration (C(eff)), which is a dominant parameter for the electrostatic forces of the RTILs, was introduced as the product of Lambda(imp)/Lambda(NMR) and the molar concentration and was compared with some physical properties, such as reported normal boiling points and distillation rates, glass transition temperature, and viscosity. A decrease in C(eff) of the RTILs is well correlated with the normal boiling point and distillation rate, whereas the liquid-state dynamics is controlled by a subtle balance between the electrostatic and other intermolecular forces.


Fate of microplastics and mesoplastics carried by surface currents and wind waves: A numerical model approach in the Sea of Japan.
A numerical model was established to reproduce the oceanic transport processes of microplastics and mesoplastics in the Sea of Japan. A particle tracking model, where surface ocean currents were given by a combination of a reanalysis ocean current product and Stokes drift computed separately by a wave model, simulated particle movement. The model results corresponded with the field survey. Modeled results indicated the micro- and mesoplastics are moved northeastward by the Tsushima Current. Subsequently, Stokes drift selectively moves mesoplastics during winter toward the Japanese coast, resulting in increased contributions of mesoplastics south of 39°N. Additionally, Stokes drift also transports micro- and mesoplastics out to the sea area south of the subpolar front where the northeastward Tsushima Current carries them into the open ocean via the Tsugaru and Soya straits. Average transit time of modeled particles in the Sea of Japan is drastically reduced when including Stokes drift in the model.


An MR-Based Model for Cardio-Respiratory Motion Compensation of Overlays in X-Ray Fluoroscopy.
In X-ray fluoroscopy, static overlays are used to visualize soft tissue. We propose a system for cardiac and respiratory motion compensation of these overlays. It consists of a 3-D motion model created from real-time magnetic resonance (MR) imaging. Multiple sagittal slices are acquired and retrospectively stacked to consistent 3-D volumes. Slice stacking considers cardiac information derived from the ECG and respiratory information extracted from the images. Additionally, temporal smoothness of the stacking is enhanced. Motion is estimated from the MR volumes using deformable 3-D/3-D registration. The motion model itself is a linear direct correspondence model using the same surrogate signals as slice stacking. In X-ray fluoroscopy, only the surrogate signals need to be extracted to apply the motion model and animate the overlay in real time. For evaluation, points are manually annotated in oblique MR slices and in contrast-enhanced X-ray images. The 2-D Euclidean distance of these points is reduced from 3.85 to 2.75 mm in MR and from 3.0 to 1.8 mm in X-ray compared with the static baseline. Furthermore, the motion-compensated overlays are shown qualitatively as images and videos.


Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells.
We examined the effects of tumor necrosis factor (TNF)-alpha on the expression and functionality of adrenomedullin (AM) receptors in cultured human coronary artery smooth muscle cells. Analysis of real-time quantitative polymerase chain reactions showed that these cells abundantly express two AM receptors comprised of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1) or RAMP2. TNF-alpha induced time- and dose-dependent decreases in the expression of CRLR and RAMP1/2 mRNAs, thereby diminishing AM-evoked cAMP production. The suppression of these three mRNAs was unaffected by inhibiting NOS, protein kinase G, protein kinase A, superoxide formation or NF-kappaB activation.


Longidorus ferrisi n. sp. from California Citrus.
In October 1999, the authors received fixed specimens of a species of Longidorus from Howard Ferris found about the roots of a citrus tree in Oakville, Napa County, CA. After determining it to be new a species, we requested additional specimens. The samples contained roughly equal numbers of males and females. Longidorus ferrisi n. sp. is most similar to L. elongatus, but can be distinguished by a greater c-ratio (111-187 vs 73-141), a lesser c´ (0.7-1.1 vs 1.0-1.3), a more offset head, a more posterior guide ring (35-40 vs 30-33 μm), the presence of sperm in the uterus in mature females, and the approximate 1:1 ratio of females to males. Other similar species include L. artemisiae, L. crassus, L. glycines, and L. milanis. Longidorus ferrisi n. sp. differs from L. artemisiae by a lesser a-ratio (74-102 vs 109-155), a lesser c´ value (0.7-1.1 vs 1.0-1.6), a more posterior guide ring (35-40 vs 27-34 μm), a longer odontostyle (91-108 vs 84-98 μm), a wider lip region (16-19 vs 14-17 μm), wider mid-body (53-69 vs 41-52 μm), and longer spicules (57-65 vs 39-49 μm). The new species differs substantially from L. crassus by its lip shape and the presence of males, and differs from L. glycines by a shorter body (4.33-5.97 vs 6.14-8.31 mm), a lesser c´ value (0.7-1.1 vs 0.9-1.4), a narrower lip region (16-19 vs 20-23 μm), wider mid-body (53-69 vs 39-57 μm), longer spicules (53-69 vs 45-53 μm), and fewer supplements (7-11 vs 11-17). Longidorus ferrisi n. sp. differs from L. milanis by a longer body (4.33-5.97vs 3.00-4.90 mm), a greater c value (111-187 vs 86-130), a wider mid-body (53-69 vs 43-56 μm), a different head shape, and longer spicules (53-69 vs 41-54 μm). The nuclear 18S ribosomal DNA sequence of this species revealed that this species is unique with respect to all sequenced Longidorus species.


Prone position as a life-saving measure for acute pulmonary haemorrhage in a young adult with cystic fibrosis.
Fatal pulmonary haemorrhage is a rare complication of cystic fibrosis. A case of unexpected life-threatening pulmonary haemorrhage is presented, and the successful management of this problem including immediate prone ventilation. Different anaesthetic techniques, avoiding endotracheal intubation and positive pressure ventilation, which may avoid similar complications, are described.


Interferon induction by influenza virus: significance of neuraminidase.
During interferon induction in mice in vivo with various strains of influenza A virus differences in titer of produced interferon were observed. Correlation between interferon titer and neuraminidase activity of a given influenza virus strain was noted. Similar correlation was demonstrated with virus fraction purified chromatographically and used for interferon induction. The fractions with high neuraminidase activity were good interferon inducers, whereas the fractions with undeterminable neuraminidase activity did not induce interferon in vivo.


Early Ciliovitreal Block following Ab Externo XEN Gel Implantation.
To report a case of ciliovitreal block following ab externo implantation of a XEN gel stent for glaucoma. Case report. An 84-year-old African American male underwent ab externo implantation of a XEN gel stent for elevated intraocular pressure. Several days after the surgery, the patient developed severe eye pain and reduced vision. Examination revealed ciliovitreal block (also called aqueous misdirection or malignant glaucoma) which was unresponsive to medical and laser treatment. Pars plana vitrectomy with anterior and posterior synechialysis and anterior chamber reformation were performed. The ciliovitreal block was resolved, and intraocular pressure brought to acceptable levels, but vision in that eye remained poor, likely due to the period of elevated pressure prior to treatment. Ciliovitreal block is a rare postsurgical (typically) form of secondary angle closure characterized by narrow or flat central and peripheral anterior chamber, anterior displacement of the lens-iris diaphragm, anterior rotation of ciliary processes, and (usually) elevated intraocular pressure. To our knowledge, this is the first reported case of ciliovitreal block occurring after ab externo XEN implantation. Early diagnosis and treatment are essential for preventing vision loss.


Total mesorectal excision with radiofrequency in rectal cancer.
The aim of this study was to compare the safety, the efficacy and the oncologic results in rectal cancer with total mesorectal excision using Ligasure (LS), a modern bipolar vessel sealing system, with monopolar electrocoagulation or stitches (ME). From July 2005 to December 2007 one hundred twenty-nine patients underwent colon resection for cancer at the San Martino Hospital of Genoa (Italy); 43 patients underwent rectal resection. All patients underwent laparotomy rectal resection with total mesorectal excision; 9 (21%, group LS) underwent total mesorectal excision with radiofrequency, 34 (79%, group ME) with monopolar electrocoagulations, vessels ligation or stitches. Patients of group LS were similar to patients of group ME in age, gender, weight and body mass index. Cancer stage was for group A 3 stage B, 5 stage C and 1 stage D, for group B 4 stage A, 15 stage B, 8 stage C, 6 stage D and 1 non-staged tumor. There were no differences in intraoperative or postoperative complications. Operating time was similar in both group. Oncological results was similar in both groups. The major cost in group LS were attributable to cost of service. The Ligasure device does not reduce operating time in laparotomy rectal cancer resection but permit correct oncological results in patients submitted to total mesorectal excision. The costs of device reserved its use to surgery of low-rectal cancer or laparoscopic approach.


Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data.
The tertiary structure for the region 1-63 of the 74 amino acid human complement protein C5a in solution was calculated from a large number of distance constraints derived from nuclear Overhauser effects with an angular distance geometry algorithm. The protein consists of four helices juxtaposed in an approximately antiparallel topology connected by peptide loops located at the surface of the molecule. The structures obtained for the helices are compatible with alpha-helical hydrogen-bonding patterns, which provides an explanation for the observed slow solvent exchange kinetics of the amide protons in these peptide regions. In contrast to the peptide region 1-63, no defined structure could be assigned to the C-terminal region 64-74, which increasingly acquires dynamic random coil characteristics as the end of the peptide chain is approached. An average root-mean-square deviation of 1.6 A was obtained for the alpha-carbons of the first 63 residues in the calculated ensemble of C5a structures, while the alpha-helices were determined with an average root-mean-square deviation of 0.8 A for the alpha-carbons. A comparison between the solution structure of C5a and the crystal structure of the functionally related C3a protein, as well as inferences for the interaction of C5a with its receptor on polymorphonuclear leukocytes, is discussed.


Acute Myocardial Infarction Due to Coronary Artery Dissection in the Postpartum Period.
Background Though rare, myocardial infarction secondary to coronary artery dissection is a life-threatening event. In reproductive age women, it commonly occurs during pregnancy or the postpartum period. Case We present a case of pregnancy-related acute myocardial infarction due to spontaneous coronary artery dissection in a 37-year-old woman who presented to the emergency room with shortness of breath and sudden onset of retrosternal chest pain 8 days after delivery of premature twins. Coronary artery catheterization showed 75 to 90% stenosis in the left main coronary artery (LMCA), extending into the proximal and mid left anterior descending (LAD) branch. The LMCA appearance in the heart catheterization was consistent with vasospasm, but it was not responsive to medical management. Subsequently, she underwent a second coronary artery catheterization and was found to have dissection requiring emergent coronary artery bypass graft × 3 in the LMCA, circumflex, and LAD that was followed by an uneventful recovery. Conclusion Early diagnosis and management of myocardial infarction due to coronary artery dissection in the peripartum period is crucial. This condition should be suspected in young reproductive age women, even in the setting of minimal risk factors. Angiography is required for diagnosis. Management should be individualized as it may include both invasive and noninvasive measures.


Osteoblastoma of the mandible mimicking osteosarcoma in FDG PET/CT imaging.
Osteoblastomas are rare tumors accounting for approximately 1% of all primary bone tumors. We report a case of osteoblastoma of the mandible with high FDG uptake. Initially, this lesion was judged as an osteosarcoma. Osteoblastomas are benign slow-growing tumors. High-resolution thin-slice CT images of the lesion as part of the PET/CT study help to characterize its morphology and extension, thus facilitating biopsy planning and resection. Approximately 25% of osteoblastomas initially have the imaging appearance of a malignant tumor. In our case, complete resection of the lesion followed by reconstruction with a bone graft was performed.


The extracellular matrix of eggshell displays anti-inflammatory activities through NF-κB in LPS-triggered human immune cells.
Avian eggshell membrane (ESM) is a natural biomaterial that has been used as an alternative natural bandage on burned and cut skin injuries for >400 years in Asian countries, and is available in large quantities from egg industries. Our aim was to characterize ESM that was separated and processed from egg waste, and to study whether this material possesses anti-inflammatory properties, making it suitable as an ingredient in industrial production of low cost wound healing products. Our results show that the processed ESM particles retain a fibrous structure similar to that observed for the native membrane, and contain collagen, and carbohydrate components such as hyaluronic acid and sulfated glycosaminoglycans, as well as N-glycans, mostly with uncharged structures. Furthermore, both processed ESM powder and the ESM-derived carbohydrate fraction had immunomodulation properties in monocytes and macrophage-like cells. Under inflammatory conditions induced by lipopolysaccharide, the ESM powder and the isolated carbohydrate fraction reduced the activity of the transcription factor nuclear factor-κB. The expression of the immune regulating receptors toll-like receptor 4 and ICAM-1, as well as the cell surface glycoprotein CD44, all important during inflammation response, were down-regulated by these fractions. Interestingly, our experiments show that the two fractions regulated cytokine secretion differently: ESM depressed inflammation by increased secretion of the anti-inflammatory cytokine IL-10 while the carbohydrate fraction reduced secretions of the pro inflammatory cytokines IL-1β and IL-6. Also, the phosphorylation of p65 and p50 subunits of nuclear factor-κB, as well as nuclear localization, differed between processed ESM powder and carbohydrate fraction, suggesting different down-stream regulation during inflammation. In conclusion, processed ESM powder and its soluble carbohydrate components possess anti-inflammatory properties, demonstrating the potential of ESM as a novel biological wound dressing for treatment of chronic inflammatory wounds.


5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.
Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. We examined the effect of the active metabolite of folic acid, 5-methyltetrahydrofolate (5-MTHF), 45 mg/week i.v. for 10 weeks, combined during the last 2 weeks with vitamin B12, 500 microg s.c. twice weekly, on homocysteinaemia and endothelial function in 15 patients undergoing convective haemodialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after administration of isosorbide dinitrate. Finally, the presence of the thermolabile variant of methyltetrahydrofolate reductase (t-MTHFR) was assessed by genotype analysis. Plasma homocysteine concentrations fell by 47% after treatment with 5-MTHF alone and by a further 13.6% after the addition of vitamin B12. The reduction was more marked in homo- and heterozygous patients than in normal genotypes for t-MTHFR. Flow-mediated endothelial vasodilation, measured by ultrasonography of the brachial artery, improved after administration of 5-MTHF (12.52+/- 2.47% vs. 7.03+/-1.65%; P<0.05), but there were no further changes following the addition of vitamin B12. Our study demonstrated that 5-MTHF administration not only reduced plasma homocysteine but also improved endothelial function in uraemic patients undergoing convective haemodialysis.


Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer.
This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.


Enhanced fluorescence cell imaging with metal-coated slides.
Fluorescence labeling is the prevailing imaging technique in cell biology research. When they involve statistical investigations on a large number of cells, experimental studies require both low magnification to get a reliable statistical population and high contrast to achieve accurate diagnosis on the nature of the cells' perturbation. Because microscope objectives of low magnification generally yield low collection efficiency, such studies are limited by the fluorescence signal weakness. To overcome this technological bottleneck, we proposed a new method based on metal-coated substrates that enhance the fluorescence process and improve collection efficiency in epifluorescence observation and that can be directly used with a common microscope setup. We developed a model based on the dipole approximation with the aim of simulating the optical behavior of a fluorophore on such a substrate and revealing the different mechanisms responsible for fluorescence enhancement. The presence of a reflective surface modifies both excitation and emission processes and additionally reshapes fluorescence emission lobes. From both theoretical and experimental results, we found the fluorescence signal emitted by a molecular cyanine 3 dye layer to be amplified by a factor approximately 30 when fluorophores are separated by a proper distance from the substrate. We then adapted our model to the case of homogeneously stained micrometer-sized objects and demonstrated mean signal amplification by a factor approximately 4. Finally, we applied our method to fluorescence imaging of dog kidney cells and verified experimentally the simulated results.


DFTMP, an NMR reagent for assessing the near-neutral pH of biological samples.
A new NMR chemical shift standard and pH indicator, difluorotrimethylsilanylphosphonic acid (DFTMP), is described, and the utility of this reagent is demonstrated for in situ determination of pH in complex biofluids. The pH dependence of this reagent allows accurate in situ determination of aqueous solution pH to within an RMSE of 0.02 pH units over a pH range of 5 to 8. Advantages of this reagent over previously described pH-sensitive components include (1) lack of metal binding affinity, (2) minimal disturbance of endogenous spectral regions, and (3) the potential to function as a multinuclear pH indicator and chemical shift reference point for 19F, 1H, and 31P nuclei. This reagent will be generally useful for NMR experiments on biological systems where the pH needs to be accurately measured at the moment of data acquisition.


Insensate versus painful diabetic neuropathy: the effects of height, gender, ethnicity and glycaemic control.
To study similarities and differences between people with insensate or painful diabetic peripheral neuropathy, particularly in relation to height, gender, ethnicity and glycaemic control. We studied prospectively 2610 patients with Type 2 diabetes attending our Diabetes Centre. Subjects were compared according to degree of sensory loss, and presence or absence of neuropathic pain. The effects of gender and ethnicity were evaluated by studying patients in different height bands. Insensate neuropathy and painful neuropathy was present in 11.4 and 3.3% of subjects, respectively. Age, duration of diabetes, height, vibration perception and HbA(1c) (P<0.0001) were independent determinants of insensate neuropathy, whereas only duration of diabetes and vibration perception (P<0.0001) were predictive of pain. There was more insensate neuropathy in males (OR 1.9) and anglo-celtics (OR 1.4) but stratification by height showed that these effects were due to height. Height has no influence on the development of pain. There is significant overlap but also considerable dichotomy in the two major forms of diabetic sensory peripheral neuropathy. The insensate type is more explainable by duration, degree of hyperglycaemia and length of peripheral nerves, factors that are likely to reflect severity of underlying structural nerve damage. Glycaemic control was not a predictor of painful neuropathy.


Adipose Tissue-Derived Stem Cells from Type 2 Diabetics Reveal Conservative Alterations in Multidimensional Characteristics.
Adipose tissue-derived mesenchymal stem cells (ASCs) are recognized as an advantaged source for the prevention and treatment of diverse diseases including type 2 diabetes mellitus (T2DM). However, alterations in characteristics of ASCs from the aforementioned T2DM patients are still obscure, which also hinder the rigorous and systematic illumination of progression and pathogenesis. In this study, we originally isolated peripancreatic adipose tissue-derived mesenchymal stem cells from both human type 2 diabetic and non-diabetic donors (T2DM-ASCs, ND-ASCs) with the parental consent, respectively. We noticed that T2DM-ASCs exhibited indistinguishable immunophenotype, cell vitality, chondrogenic differentiation and stemness as ND-ASCs. Simultaneously, there's merely alterations in migration and immunoregulatory capacities in T2DM-ASCs. However, differing from ND-ASCs, T2DM-ASCs exhibited deficiency in adipogenic and osteogenic differentiation, and in particular, the delayed cell cycle and different cytokine expression spectrum. The conservative alterations of T2DM-ASCs in multifaceted characteristics indicated the possibility of autologous application of ASCs for cell-based T2DM treatment in the future.


A Comparison Study of Canonical Correlation Analysis Based Methods for Detecting Steady-State Visual Evoked Potentials.
Canonical correlation analysis (CCA) has been widely used in the detection of the steady-state visual evoked potentials (SSVEPs) in brain-computer interfaces (BCIs). The standard CCA method, which uses sinusoidal signals as reference signals, was first proposed for SSVEP detection without calibration. However, the detection performance can be deteriorated by the interference from the spontaneous EEG activities. Recently, various extended methods have been developed to incorporate individual EEG calibration data in CCA to improve the detection performance. Although advantages of the extended CCA methods have been demonstrated in separate studies, a comprehensive comparison between these methods is still missing. This study performed a comparison of the existing CCA-based SSVEP detection methods using a 12-class SSVEP dataset recorded from 10 subjects in a simulated online BCI experiment. Classification accuracy and information transfer rate (ITR) were used for performance evaluation. The results suggest that individual calibration data can significantly improve the detection performance. Furthermore, the results showed that the combination method based on the standard CCA and the individual template based CCA (IT-CCA) achieved the highest performance.


St. John's Wort (Hypericum perforatum) stimulates human osteoblastic MG-63 cell proliferation and attenuates trabecular bone loss induced by ovariectomy.
The effect of St. John's Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. Proliferation, expression of estrogen receptor (ER) α and ER β, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, β-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham operated rats were treated with vehicle only (Sham-C). Serum ALP and C-telopeptide (CTX), and femoral trabecular bone loss were examined. SJW increased MG-63 cell proliferation and expression of ER α and ER β, and positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed estrogen like effect on bone associated with slowing down in trabecular bone loss. Histopathology by H&E showed rats treated with SJW displayed denser structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW was shown to reduce serum CTX in OVX rats. The present study provides new insight in preventing estrogen deficiency induced bone loss of SJW and possibility for its application in bone health supplement.


Signs of Pretense Across Age and Scenario.
Participation in imagined worlds is a hallmark of the human species, and yet we know little about the context of its early emergence. The experiments reported here replicated and extended in 2 directions Lillard and Witherington's (2004) study of how mothers pretend to have snacks, across different ages of children (15- to 24-month-olds, Experiment 1) and to a different scenario (personal grooming, Experiment 2). Mothers' pretend behaviors changed little as infants aged, but there were some scenario differences. Most striking in this research was the consistency with which particular maternal pretend behaviors were associated with children engaging in pretense behaviors and smiling. The findings are discussed with reference to the child's emerging skills in joint attention and social referencing.


Adsorption and mechanism of cellulase enzymes onto lignin isolated from corn stover pretreated with liquid hot water.
In the bioconversion of lignocellulosic substrates, the adsorption behavior of cellulase onto lignin has a negative effect on enzymatic hydrolysis of cellulose, decreasing glucose production during enzymatic hydrolysis, thus decreasing the yield of fermentation and the production of useful products. Understanding the interaction between lignin and cellulase is necessary to optimize the components of cellulase mixture, genetically engineer high-efficiency cellulase, and reduce cost of bioconversion. Most lignin is not removed during liquid hot water (LHW) pretreatment, and the characteristics of lignin in solid substrate are also changed. To understand the interactions between cellulase and lignin, this study investigated the change in the characteristics of lignin obtained from corn stover, as well as the behavior of cellulase adsorption onto lignin, under various severities of LHW pretreatment. LHW pretreatment removed most hemicellulose and some lignin in corn stover, as well as improved enzymatic digestibility of corn stover. After LHW pretreatment, the molecular weight of lignin obviously increased, whereas its polydispersity decreased and became more negative. The hydrophobicity and functional groups in lignin also changed. Adsorption of cellulase from Penicillium oxalicum onto lignin isolated from corn stover was enhanced after LHW pretreatment, and increased under increasing pretreatment severity. Different adsorption behaviors were observed in different lignin samples and components of cellulase mixtures, even in different cellobiohydrolases (CBHs), endo-beta-1, 4-glucanases (EGs). The greatest reduction in enzyme activity caused by lignin was observed in CBH, followed by that in xylanase and then in EG and β-Glucosidase (BGL). The adsorption behavior exerted different effects on subsequent enzymatic hydrolysis of various biomass substrates. Hydrophobic and electrostatic interactions may be important factors affecting different adsorption behaviors between lignin and cellulase. LHW pretreatment changed the characteristics of the remaining lignin in corn stover, thus affected the adsorption behavior of lignin toward cellulase. For different protein components in cellulase solution from P. oxalicum, electrostatic action was a main factor influencing the adsorption of EG and xylanase onto lignin in corn stover, while hydrophobicity affected the adsorption of CBH and BGL onto lignin.


Cardiovascular Effects of Cydonia oblonga Miller (Quince).
Cydonia oblonga Miller (quince) is a monotypic genus in the Rosaceae family which used to treat or prevent many medical conditions such as diabetes, cancer, infections, and ulcer. This review will summarize the current state of knowledge available on botany, phytochemistry, and pharmacology of this plant with a focus on its effect on some cardiovascular risk factors such as diabetes, blood pressure, lipid profile, and body weight. Databases of Google Scholar, Web of Science, PubMed, Scopus, and SID were searched systematically for English published articles with no date limitation. There were no human studies found, and all of the studies were conducted on animals or in vitro models. Reviewing of all 12 included articles showed that different types of quince extract have positive effects on cardiovascular-related factors such as blood pressure, diabetes, glucose metabolism, lipid profile, ROS, body weight, liver dysfunction, and thrombosis. An antihypertensive effect of quince showed to be a magnitude that is comparable to captopril and the lipid-lowering effect of quince showed to be a magnitude that is comparable to simvastatin. However, two studies evaluated the effect of quince fruit extract on insulin levels; one of them reported no positive effect, and the other one reported a significant positive effect. It can be concluded that different parts of quince including leaf, seed, and fruit could be used for improving cardiovascular-related factors including blood pressure, glucose metabolism and diabetes, obesity, and lipid-adjusting purposes. Quince was also found to have strong anti-inflammatory and antioxidant capacity. This study paves the way for further studies on the cardiovascular effect of quince consumption as a beneficial nutraceutical in humans.


Relative changes in flow velocities in vasospasm after subarachnoid hemorrhage: a transcranial Doppler study.
Transcranial Dopplers (TCDs) have been used to monitor cerebral blood flow velocities in subarachnoid hemorrhage (SAH).The purpose of our two-part study was to compare the reliability of relative increases in flow velocities with conventionally used absolute flow velocity indices and to correct for hyperemia-induced flow velocity change. Part 1: Charts of 50 patients admitted to Hahnemann University Hospital with aneurismal SAH were reviewed. Mean middle cerebral artery maximum flow velocities (MCA-MFV) were reviewed for initial flow velocities (IFVs) and maximal flow velocities (MFVs) that were reached during hospital course. Correlating flow velocities (SFVs) were noted in patients who developed symptomatic vasospasm. MFV/IFV and SFV/IFV ratios were calculated to evaluate relative changes in flow velocity. Part 2: Correction for hyperemia was derived from Lindegaards Ratio using extracranial internal carotid artery (ICA) flow velocity ratio (corrected MCA-MFV/observed MCA-MFV = EC-ICAFV (day1)/observed EC-ICAFV). Part 1: All 10 patients who developed symptomatic vasospasm exhibited a twofold increase (SFV/IFV: >2) in flow velocities prior to developing symptomatic vasospasm, and 5 patients had a threefold increase (SFV/IFV: >3). Of the 40 patients who did not develop symptomatic vasospasm, 33 patients did not have a twofold increase in their flow velocities at any time. The positive predictive value for MFV/IFV greater than 3 (n = 6) and SFV/IFV greater than 3 (n = 5) was 100%. The negative predictive value for MFV/IFV less than 2 (n = 33) was 100%. Data using relative changes (twofold increase) in flow velocity was more sensitive (100 to 90%), specific (83 to 70%), and predictive (positive predictive value [PPV]: 59 to 45%; negative predictive value [NPV]: 100 to 97%) for symptomatic vasospasm than absolute flow velocity indices using MCA-MFV greater than 120 even in combination with Lindegaards Ratio (MCA/ICA greater than 3). Part 2: Correction for hyperemia by modifying Lindegaard's Index in the 32 patients where data was available improved the PPV of absolute flow velocities from 44 to 62%. In this population, the application of this equation while evaluating relative change in flow velocities improved PPV of twofold increase from 57 to 73%. Relative changes in flow velocities in patients with aneurysmal SAH correlated better with clinically significant vasospasm than absolute flow velocity indices. Correction for hyperemia improved predictive value of TCD in vasospasm.


The radiographic position of medial and lateral meniscal horns as a basis for meniscal reconstruction.
This investigation attempted to determine the radiographic position of human meniscal horn bony insertion sites. This information would prove vital for anatomically correct osseous tunnel placement necessary for the restoration of a functional meniscus after reconstructive surgery. The native bony insertion sites of the medial and lateral meniscus in 13 fresh-frozen human cadaver knees were radiographically examined. After insertion site outline with 22-gauge fine wire, anteroposterior and lateral radiographs were obtained. Radiographic landmarks were then described in detail. Each meniscal horn was found to have a distinct bony insertion site with characteristic and consistent radiographic landmarks defining its margins. Using an arthroscopic guide, 3/32-inch fine wires were drilled into the center of the lateral (5 specimens) and medial (5 specimens) meniscal horns to validate these locations and to establish the clinical usefulness of these measures. Improved understanding of meniscal horn insertion site locations should improve osseous tunnel placements during meniscal transplantation. In the presence of a properly sized allograft, anatomically correct tunnel placement increases the likelihood of restoring normal meniscal function.


Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes.
A trifunctional bispecific antibody (BiLu) directed against murine CD3 and human epithelial-cell adhesion molecule (EpCAM) was tested for its ability to improve cell-mediated adoptive immunotherapy in a murine model of B16 melanoma cells transfected with human EpCAM. Intraperitoneal inoculation of naive C57BL/6 (C57) splenocytes induced lethal graft versus host disease (GVHD) in 85% to 97% of sublethally irradiated (BALB/c x C57BL/6) F1 (F1) hosts inoculated intraperitoneally with a sublethal or lethal dose of melanoma cells. BiLu antibodies given intraperitoneally concomitantly with alloreactive C57 cells effectively prevented GVHD-related and tumor-related death in 16 of 25 F1 mice inoculated with a sublethal tumor-cell dose and in 10 of 20 mice inoculated with a lethal tumor-cell dose over a follow-up period of more than 200 days. BiLu treatment also efficiently prevented severe GVHD, which was induced by high doses of BALB/c-derived splenocytes. Trifunctional bispecific antibodies (TbsAbs) capable of cross-linking T lymphocytes, natural killer, and other FcgammaR-positive effector cells, via their Fc region, to the tumor cells may be applied together with adoptive allogeneic-cell therapy to maximize antitumor responses while acting on GVHD in patients with minimal residual disease.


Determination of serum neutralization antibodies against seasonal influenza A strain H3N2 and the emerging strains 2009 H1N1 and avian H5N1.
Humoral virus neutralizing activity is crucial in preventing influenza virus infection. However, the influenza neutralizing activity in the general population remains unclear. In this study we performed a serological survey of 200 blood donors from Guangzhou, China. Using a microneutralization (MN) assay, neutralizing activities against influenza A 2009 H1N1, H3N2 and H5N1 were measured. Anti-haemagglutinin antibody was assayed by haemagglutination inhibition (HI) test. Also, antibodies against M1 and M2 matrix proteins were measured using an enzyme-linked immunosorbent assay (ELISA). By MN assay, 86% of the individuals showed neutralizing activity against H3N2, 11% against 2009 H1N1, and none against H5N1. The positive rate for H3N2 increased as the age of individuals increased. Interestingly, males displayed a 4 times higher positive rate against 2009 H1N1 than females. The results of ELISA revealed that 97.5% of the individuals had positive M1 titres and 21% had positive M2 titres. Furthermore, anti-haemagglutinin antibody had a much higher correlation with the neutralization activity than anti-M1 and anti-M2 antibodies. Neutralizing activities against H5N1 and 2009 H1N1 were low in the general population. Therefore, public health agencies should design strategies for preventing potential H5N1 and 2009 H1N1 pandemics.


[Microscopic colitis--more common cause of diarrhea than believed. Biopsies are the only way to diagnosis, drug treatment is effective].
Microscopic colitis, encompassing collagenous and lymphocytic colitis, is a fairly common cause of chronic watery diarrhoea, especially in elderly women. In recent epidemiological studies the annual incidence of each disorder was 4-6/100.000 inhabitants. The aetiology is unknown. The main clinical symptoms are watery diarrhoea, weight loss and abdominal pain. Laboratory analyses are nondiagnostic, and the diagnoses rely on histopathological examination of colonic mucosal biopsies. There is an association to autoimmune diseases such as thyroid disorders, diabetes mellitus, celiac disease and arthritis. Budesonide is the best-documented treatment of collagenous colitis. It is superior to placebo in short-term therapy, but the long-term efficacy is not well studied. The evidence for other therapeutic alternatives such as loperamide, cholestyramine, bismuth subsalicylate, or 5-aminosalicylates is weak. In unresponsive severe disease azathioprine or methotrexate may be tried. There are at present no controlled data on the treatment of lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality.


Hyaluronan/Collagen Hydrogels with Sulfated Hyaluronan for Improved Repair of Vascularized Tissue Tune the Binding of Proteins and Promote Endothelial Cell Growth.
Innovative biomaterial-based concepts are required to improve wound healing of damaged vascularized tissues especially in elderly multimorbid patients. To develop functional hydrogels as 3D cellular microenvironments and as carrier or scavenging systems, e.g., for mediator proteins or proinflammatory factors, collagen fibrils are embedded into a network of photo-crosslinked acrylated hyaluronan (HA), chondroitin sulfate (CS), or sulfated HA (sHA). After lyophilization, the gels show a porous structure and an improved stability against degradation via hyaluronidase. Gels with CS and sHA bind significantly more lysozyme than HA/collagen gels and retard its release. The proliferation and metabolic activity of endothelial cells are significantly increased on sHA gels compared to CS- or only HA-containing hydrogels. These findings highlight the potential of HA/collagen hydrogels with sulfated glycosaminoglycans to tune the protein binding and release behavior and to directly modulate cellular response. This can be easily translated into biomimetic biomaterials with defined properties to stimulate wound healing.


VMS-ROT: A New Module of the Virtual Multifrequency Spectrometer for Simulation, Interpretation, and Fitting of Rotational Spectra.
The Virtual Multifrequency Spectrometer (VMS) is a tool that aims at integrating a wide range of computational and experimental spectroscopic techniques with the final goal of disclosing the static and dynamic physical-chemical properties "hidden" in molecular spectra. VMS is composed of two parts, namely, VMS-Comp, which provides access to the latest developments in the field of computational spectroscopy, and VMS-Draw, which provides a powerful graphical user interface (GUI) for an intuitive interpretation of theoretical outcomes and a direct comparison to experiment. In the present work, we introduce VMS-ROT, a new module of VMS that has been specifically designed to deal with rotational spectroscopy. This module offers an integrated environment for the analysis of rotational spectra: from the assignment of spectral transitions to the refinement of spectroscopic parameters and the simulation of the spectrum. While bridging theoretical and experimental rotational spectroscopy, VMS-ROT is strongly integrated with quantum-chemical calculations, and it is composed of four independent, yet interacting units: (1) the computational engine for the calculation of the spectroscopic parameters that are employed as a starting point for guiding experiments and for the spectral interpretation, (2) the fitting-prediction engine for the refinement of the molecular parameters on the basis of the assigned transitions and the prediction of the rotational spectrum of the target molecule, (3) the GUI module that offers a powerful set of tools for a vis-à-vis comparison between experimental and simulated spectra, and (4) the new assignment tool for the assignment of experimental transitions in terms of quantum numbers upon comparison with the simulated ones. The implementation and the main features of VMS-ROT are presented, and the software is validated by means of selected test cases ranging from isolated molecules of different sizes to molecular complexes. VMS-ROT therefore offers an integrated environment for the analysis of the rotational spectra, with the innovative perspective of an intimate connection to quantum-chemical calculations that can be exploited at different levels of refinement, as an invaluable support and complement for experimental studies.


[An new application of gait analysis: guidance in finding the underlying health condition].
Instrumented gait analysis was developed to assist in clinical decision-making to optimise treatment to improve walking in patients with complex gait problems. In this clinical lesson, two cases are presented in which instrumented gait analysis was used for a different goal. It was used to assist in finding the correct neurological or orthopaedic diagnosis in patients in whom symptoms occurred during walking. In both patients, an accurate diagnosis could not be found based on the symptoms they reported, despite a thorough analysis by the neurologist. Instead, the symptoms were caused by the compensations patients used to optimise walking and not directly by the health condition itself. Through instrumented gait analysis, the direct impact of a health condition on the gait pattern can be distinguished from compensations. It can be an asset in finding the correct diagnosis, especially in patients with complex gait problems or multiple health conditions.


The high-velocity core of the Western boundary undercurrent at the base of the u.s. Continental rise.
The Western Boundary Undercurrent is a high-velocity, contour-following bottom current that flows southwesterly on the U.S. Atlantic continental margin. A high-velocity core of the Western Boundary Undercurrent is delineated by an analysis of underlying sediments, which are characterized by coarse particle sizes and efficiently aligned magnetic grains in a zone from 4440 meters at the base of the rise to 5200 meters on the adjacent abyssal plain.


F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Muscle Uptake in Antiglutamic Acid Decarboxylase Antibody-positive Stiff-person Syndrome.
Antiglutamic acid decarboxylase-65 (anti-GAD65) autoantibodies have been identified in variety of rare neurologic disorders most frequently in stiff-person syndrome (SPS), condition characterized by muscle rigidity and overlying painful spasms, typically affecting axial and limb musculature. In anti-GAD65-related neurologic disorder, malignancy screening is often performed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Here, we present an interesting image of 18FFDG PET/CT whole body showing muscle uptake and FDG brain showing thalamic hypometabolism in SPS.


Isolation of RD-114-like oncornavirus from a cat cell line.
A clone of cells derived from a continuous line of cat cells (CCC) spontaneously produced an RNA C-type virus (CCC virus) which did not have the group-specific antigen of the standard strains of feline leukemia viruses but did have that of the RD-114 virus. Single-hit infection of a virus yielding CCC cell with only the feline leukemia virus pseudotype of murine sarcoma virus [MSV(FeLV)] resulted in the release of a pseudotype of MSV coated with the CCC virus envelope. Host range, transmission of virus, helper functions, interference properties, and specific neutralization showed that the CCC and the RD-114 isolates as well as their respective MSV pseudotypes are closely similar if not identical. Parental, virus-negative cells frozen before the existence of RD-114 were chemically induced to yield CCC-like virus de novo. Infection of susceptible human cells with the chemically induced virus resulted in interference with the CCC virus pseudotype of MSV but not with the FeLV pseudotype of MSV.


Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy.
We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff's base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy.


Uptake, removal, accumulation, and phytotoxicity of phenol in willow trees (Salix viminalis).
Phenol is an intermediate in the metabolism of plants, but it also is a high-volume production compound frequently found in the environment. The relation between removal, uptake, accumulation, and toxicity of phenol in willow trees (Salix viminalis) was determined. Willows were exposed to phenol levels up to 1000 mg/L in hydroponic solution and sand, respectively. The change on water transpiration of the trees was used to determine toxic effects. In both hydroponic solution and sand, only small inhibition of transpiration was detected up to phenol concentrations of 250 mg/L. For concentrations of 500 mg/L or greater, transpiration fell to 50% or less, and the trees wilted. The trees exposed to 1000 mg/L wilted and eventually died. For initial nominal concentrations of 1000 mg/L, a significantly higher amount of phenol remained at the end of the experiment compared to the amount remaining with all other concentrations. Phenol loss was approximately 90% for the trees that survived, except for trees exposed to the lowest concentration (10 mg/L). The loss of phenol was only 15 to 18% in experiments performed without trees. The results demonstrate a clear relation between removal, accumulation, and toxic effects of phenol in trees. Phenol levels of less than 250 mg/L could be degraded by "in planta" metabolism; therefore, no significant buildup of phenol nor any toxic effects in plants occurred. With higher levels, phenol was still degraded quickly, but an accumulation in trees accompanied by severe toxic effects occurred. Phytoremediation of phenol would be best with concentrations in water or soil solution of less than 250 mg/L, at which the degradation of phenol by willows or associated bacteria is rapid and efficient and the toxic effects on trees are negligible.


Antiradical efficiency of Maillard reaction mixtures in a hydrophilic media.
The Maillard reaction (MR) has a clear impact in food science, nutrition, and medical research. Free radical scavenging capacities of several MR mixtures made from single combinations of glucose or lactose and amino acids (gly, his, lys, trp, met, and cys) were evaluated by using the N,N-dimethyl-p-phenylenediamine radical cation assay. Medium-roasted coffee brew was used as reference of a thermally processed food. A novel approach has been applied in order to get more information about the kinetic behavior of the radical scavenging properties of MR mixtures in a watery environment. Antiradical efficiency (AE) concept has been applied, and it takes into consideration the reaction time, apart from the amount of antioxidant necessary to decrease by 50% the radical initial concentration (EC(50)). Cysteine and histidine reveal as powerful amino acids to exert a high AE in the MR mixtures. No relationship between AE parameter and browning was observed.


Interventions for replacing missing teeth: dental implants in zygomatic bone for the rehabilitation of the severely deficient edentulous maxilla.
Dental implants are used for replacing missing teeth. Placing dental implants is limited by the presence of adequate bone volume permitting their anchorage. Several bone augmentation procedures have been developed to solve this problem. Zygomatic implants are long screw-shaped implants developed as a partial or complete alternative to bone augmentation procedures for the severely atrophic maxilla. One to three zygomatic implants can be inserted through the posterior alveolar crest and maxillary sinus to engage the body of the zygomatic bone. A couple of conventional dental implants are also needed in the frontal region of the maxilla to stabilize the prosthesis. The potential main advantages of zygomatic implants could be that in some situations bone grafting may not be needed and a fixed denture could be fitted sooner. Another specific indication for using zygomatic implants could be the need of maxillary reconstruction after maxillectomy in cancer patients. To test the hypothesis of no difference in outcomes between zygomatic implants with and without bone augmenting procedures in comparison with conventional dental implants in augmented bone for severely resorbed maxillae. We searched the Cochrane Oral Health Group's Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We handsearched several dental journals. No language restrictions were applied. Personal contacts and all known zygomatic implant manufacturers were contacted to identify unpublished trials. Most recent search: May 2005. Randomised controlled clinical trials (RCTs) including patients with severely resorbed maxillae who could not be rehabilitated with conventional dental implants, treated with zygomatic implants with and without bone grafts versus patients treated with conventional dental implants in conjunction with bone augmentation procedures having a follow up of at least 1 year. Outcome measures considered were: prosthesis and implant failures, side effects, patient satisfaction and cost effectiveness. Screening of eligible studies, assessment of the methodological quality of trials and data extraction were to be conducted in duplicate and independently by two authors. Results were to be expressed as random-effects models using weighted mean differences for continuous outcomes and risk ratio for dichotomous outcomes with 95% confidence interval. Heterogeneity was to be investigated including both clinical and methodological factors. No RCTs or controlled clinical trials (CCTs) were identified. There is the need for RCTs in this area to assess whether zygomatic implants offer some advantages over alternative bone augmentation techniques for treating atrophic maxillae.


Organogenesis of the Harderian gland: a comparative survey.
Although research interest in the Harderian gland (HG) has increased during the last few years, only a small amount of information exists about its organogenesis. In mouse the HG appears in the posterior part of eye region, in the form of nonluminated tubules between the sixteenth and eighteenth days of gestation. At birth it is still not differentiated histologically. In birds the HG originates from the conjunctival epithelium at a late embryonic stage. In the English sparrow, Passer domesticus (incubation period of about 13 days), it appears between the seventh and the eighth days of incubation. In the chick embryo (incubation period of about 21 days) it originates between the eleventh and the twelfth days. Among reptiles the lizard Podarcis s. sicula has proved to be a useful model to clarify the embryological origin of the orbital glands since it possesses the anterior lacrimal gland contiguous to the HG in the medial corner of the orbit. The anlage of the orbital glands appears on about the twenty-second day of development (incubation period of about 43 days) in the form of a short tubule projecting from the conjunctival epithelium, at the time of development of the nictitating membrane. At this stage the mesenchymal cells surrounding the glandular blastema form a well-defined sac, later occupied by the orbital glands. From this stage until hatching the growth of the glandular blastema continues with the formation of acini which move posteriorly into the preformed mesenchymal sac. At the thirty-sixth day of development the more lateral acini differentiate into the HG. Only at the forty-first day do the more medial acini differentiate into the anterior lacrimal gland. At hatching the HG is fully differentiated. In anuran amphibia the primordium of the HG appears during the metamorphosis at the time of development of the nictitating membrane.


Total synthesis of a novel tetracyclic alkaloid, cassiarin F from the flowers of Cassia siamea.
A novel alkaloid, cassiarin F (1), which showed potent antiplasmodial activity against Plasmodium falciparum in vitro, was isolated from the flowers of Cassia siamea, and its structure was elucidated on the basis of 2D NMR analyses. A total synthesis of 1 was also achieved by employing the Suzuki coupling constructing biaryl unit, nucleophilic aromatic substitution, and Houben-Hoesch type ring construction as key steps.


Tracheobronchial anomalies in a patient with Schimke immuno-osseous dysplasia (SIOD).
Schimke Immuno-osseous Dysplasia (SIOD) is a rare genetic disorder with multiple systemic manifestations. Pulmonary manifestations have been described but not well characterized. They are believed to be secondary to decreased elasticity, and include emphysema, pulmonary hypertension and bronchiectasis. We describe a 24-year-old female patient with SIOD with tracheobronchial anomalies not reported before, including tracheomalacia and a tracheal bronchus with Epstein-Barr virus (EBV) related leiomyoma causing endobronchial obstruction. Such anomalies, in addition to the difficult upper airway associated with SIOD present specific challenges during management. This case reports documents tracheobronchial abnormalities that have not been described before in SIOD.


Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis.
It has been recently shown that the catecholamine neurotransmitter dopamine (DA) strongly and selectively inhibits vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-induced angiogenesis. Gastric cancer is highly angiogenic and is dependent on VEGF for its growth and progression. Because substantial amounts of DA present in normal stomach tissues has been implicated in several gastric functions, we therefore investigated the role, if any, of this neurotransmitter in the growth and progression of gastric cancer. Initially, the status of DA and tyrosine hydroxylase, the rate-limiting enzyme required for DA synthesis, were determined in human gastric cancer tissues and in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer tissues of rats. On the basis of our observation of inverse correlation between stomach DA and gastric cancer growth, we determined the effect of pharmacological dose of DA on the angiogenesis and growth of MNNG induced gastric cancer in rats and Hs746T human gastric cancer in nude mice. DA and tyrosine hydroxylase were absent in both human and rat gastric cancer tissues. On the contrary, a low nontoxic pharmacological dose of DA significantly retarded tumor angiogenesis by inhibiting VEGFR-2 phosphorylation in tumor endothelial cells, which expressed DA D(2) receptors. This action of DA was associated with the growth inhibition of both MNNG-induced rat malignant gastric tumors and xenotransplanted human gastric cancer in nude mice. Our study demonstrates that there is an inverse correlation between endogenous stomach DA and gastric cancer and indicates that DA already in clinical use for other purposes might have a role as an antiangiogenic agent in the treatment of gastric cancer.


Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.
This retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval. Eighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival. Retreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156). Our data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed.


Process and detection in fraud and deceit.
There has been considerable interest recently in scientific misconduct. Although much has been written and discussed about specific cases, very little, if any, research has been carried out on the process of fraud. An understanding of this aspect can contribute much to methods of detection and lead to recommendations for preventing misconduct and for implementation of appropriate sanctions where fraud has been detected and proved. In this article I initiate a study of the process of fraud using a series of case studies. Hypotheses are generated by methods pioneered by Peirce and most recently developed and thoroughly discussed by Glaser and Strauss under the name of grounded theory. Some illustrations of what can be learned from such studies are included.


Analysis of tracheal intubation in out-of-hospital helicopter emergency medicine recorded by video laryngoscopy.
Tracheal intubation remains the gold standard of airway management in emergency medicine and maximizing safety, intubation success, and especially first-pass intubation success (FPS) in these situations is imperative. We conducted a prospective observational study on all 12 helicopter emergency medical service (HEMS) bases of the Swiss Air Rescue, between February 15, 2018, and February 14, 2019. All 428 patients on whom out-of-hospital advanced airway management was performed by the HEMS crew were included. The C-MAC video laryngoscope was used as the primary device for tracheal intubation. Intubation procedures were recorded by the video laryngoscope and precise time points were recorded to verify the time necessary for each attempt and the overall procedure time until successful intubation. The videos were further analysed for problems and complications during airway management by an independent reviewer. Additionally, a questionnaire about the intubation procedure, basic characteristics of the patient, circumstances, environmental factors, and the provider's level of experience in airway management was filled out. Main outcome measures were FPS of tracheal intubation, overall success rate, overall intubation time, problems and complications of video laryngoscopy. FPS rate was 87.6% and overall success rate 98.6%. Success rates, overall time to intubation, and subjective difficulty were not associated to the providers' expertise in airway management. In patients undergoing CPR FPS was 84.8%, in trauma patients 86.4% and in non-trauma patients 93.3%. FPS in patients with difficult airway characteristics, facial trauma/burns or obesity ranges between 87 and 89%. Performing airway management indoors or inside an ambulance resulted in a significantly higher FPS of 91.1% compared to outdoor locations (p < 0.001). Direct solar irradiation on the screen, fogging of the lens, and blood on the camera significantly impaired FPS. Several issues for further improvements in the use of video laryngoscopy in the out-of-hospital setting and for quality control in airway management were identified. Airway management using the C-MAC video laryngoscope with Macintosh blade in a group of operators with mixed experience showed high FPS and overall rates of intubation success. Video recording emergency intubations may improve education and quality control.


Online reprint request: search, access, read, and update.
Online reprint request (ORR) is the standard protocol to obtain the reprints (e-print/hard copy) using the internet (author's e-mail address) when the required literature is not available. The problem of higher cost of surface mail for the author and the reader, as well as the time taken to receive postal reprints, is overcome by ORR. This technique has its limitation in message failure, expiration of mail (e-mail decay), or journal not providing author's e-mail address. This article analyzes the available practical solution to overcome these barriers. This process facilitates the exchange of scientific information. In e-mail decay, reprint request can be sent in the following order: a) search and send to author's latest e-mail address, b) co-author's latest or affiliated institution's e-mail address, c) postal reprint request providing the requestor's e-mail address. This protocol can be practiced when library facilities or required literature is not available. Literature can be pooled and used for residency teaching programs, like group discussions, journal clubs, and e-learning exercises (teleeducation), to update the recent advances for practice and research.


Partial airway obstruction following manufacturing defect in laryngeal mask airway (Laryngeal Mask Silken™).
Laryngeal mask (LM) airway is commonly used for securing airway in day-care surgeries. Various problems have been described while using LM airway. Out of those, mechanical obstruction causing airway compromise is most common. Here, we describe a case report of 4-year-old child who had partial upper airway obstruction due to LM manufacturer's defect. There was a silicon band in upper one-third of shaft of LM airway. This band was made up of the same material as that of LM airway so it was not identifiable on external inspection of transparent shaft. We suggest that such as non-transparent laryngeal mask, a transparent LM airway should also be inspected looking inside the lumen with naked eyes or by using a probe to rule out any manufacturing defect before its insertion.


Where does Pelvic and Acetabular Fracture Treatment fit into the Newly Proposed Major Trauma Model in Ireland?
Aim To provide the most up to date reference of referral patterns for pelvis and acetabular (PA) fractures in Ireland and discuss where services should ideally be located. Methods A retrospective review was conducted of all referrals to the national referral centre for PA fractures in Ireland for 2016 and 2017. Results Over the two-year study period 456 referrals were made. Mean age of patients was 53 years, 62.9% were male. Management was conservative in 60.7%, operative in 38.2% while 1.1% died prior to transfer. Nearly half of fractures (47.8%) were due to falls with 38.6% due to road trauma. Referrals from the proposed central trauma network accounted for 76.1% of referrals. Median length of stay was 7 days. Average cost of operative treatment was €11,774. Conclusions PA trauma is associated with significant morbidity and costs to both patients and society. Consideration needs to be given to where best to place PA services to ensure the highest quality care in this cohort of patients


New Direct-Acting Antiviral Agents and Immunomodulators for Hepatitis B Virus Infection.
Chronic hepatitis B (CHB) affects over 350 million individuals worldwide and is the most common cause of liver cancer. In the United States, CHB affects at least 2 to 3 million individuals, and current therapies can control the disease but not cure it. There are over 30 new molecules being studied in CHB in preclinical to phase 2 studies, targeting specific parts of the hepatitis B virus (HBV) life cycle and the host immune response. When discussing new therapies for CHB, it is critical to understand both the various phases of CHB and the life cycle of HBV. This article will discuss both of these issues, as well as mechanisms of action of potential therapies and possible ways to combine such therapies in the various phases of CHB.


Theory of Light-Modulated Emission Spectroscopy.
Perovskite solar cells and fluorescent collectors formed by a dispersion of quantum dots in a transparent solid are paradigmatic devices for photon capture and utilization that involve the coupling of photon displacement, absorption and regeneration. In order to obtain information about the coupled photonic processes in systems involving photon recycling, we analyze the transfer function for modulated outgoing to incoming photon flux. We show the physical features of light-to-light impedance that reveals a trap-limited diffusion of photons coupled with the nonradiative recombination. The spectral shapes allow one to distinguish readily photonic recombination and diffusion kinetic phenomena and consequently to determine the physical parameters that control the system's quantum yield for photoluminescence.


Animal welfare: a complex domestic and international public-policy issue--who are the key players?
Animal-welfare issues are usually portrayed in the media in a black-and-white fashion, with simple, single-perspective solutions proposed for what are often, in fact, complex policy issues. In this article, we argue that animal welfare is a multifaceted international and domestic public-policy issue that must take account of not only scientific, ethical, and economic issues but also religious, cultural, and international trade policy considerations. Management of animal welfare at a government policy level also requires an approach based on incremental change. Such change must be both science based and ethically principled, and the rate of change must recognize both the expectations of society and the constraints on the animal user. Ideally, such change should involve full ownership and buy-in from the affected animal user group. The range of stakeholders involved in the animal-welfare debate includes industry and producer groups, science bodies, and animal-welfare non-governmental organizations and professional groups, including the veterinary and legal professions. The veterinary profession, in particular, is expected to play an animal-welfare leadership role, and we discuss expectation versus reality at both a national and an international level. This latter discussion includes specific reference to the role of the World Organisation for Animal Health (the OIE) as an intergovernmental organization representing 175 countries and details some of the major achievements since the OIE assumed its international animal-welfare standard-setting role in 2002. We also address the role of the veterinary profession at national, regional, and international levels.


Management of splenic trauma at a rural, Level I trauma center.
The spleen is the most commonly injured organ in blunt abdominal trauma. There remains much controversy in the diagnosis and management of the injured spleen, with a recent trend toward nonoperative management. A 5-year period was reviewed at a rural, Level I trauma center to address issues of operative versus nonoperative management. During this time period, there were 136 patients identified as having trauma to the spleen. Most (95%) were the result of blunt trauma, and a majority of these were from motor vehicle accidents. Computed tomography was the most frequent method of diagnosis. Approximately half of the patients underwent immediate operative intervention. Of those initially observed, 10 patients (16%) eventually were operated on. Most of the cases were due to underestimation of the severity of the splenic injury, and most received blood transfusion. This experience suggests that observation for splenic trauma is appropriate in many cases, as long as the surgeon is certain the spleen is not actively bleeding and the patient will not require blood transfusion.


The cation-responsive protein NhaR of Escherichia coli activates pgaABCD transcription, required for production of the biofilm adhesin poly-beta-1,6-N-acetyl-D-glucosamine.
The pgaABCD operon of Escherichia coli is required for production of the biofilm adhesin poly-beta-1,6-N-acetyl-d-glucosamine (PGA). We establish here that NhaR, a DNA-binding protein of the LysR family of transcriptional regulators, activates transcription of this operon. Disruption of the nhaR gene decreased biofilm formation without affecting planktonic growth. PGA production was undetectable in an nhaR mutant strain. Expression of a pgaA'-'lacZ translational fusion was induced by NaCl and alkaline pH, but not by CaCl(2) or sucrose, in an nhaR-dependent fashion. Primer extension and quantitative real-time reverse transcription-PCR analyses further revealed that NhaR affects the steady-state level of pga mRNA. A purified recombinant NhaR protein bound specifically and with high affinity within the pgaABCD promoter region; one apparent binding site overlaps the -35 element, and a second site lies immediately upstream of the first. This protein was necessary and sufficient for activation of in vitro transcription from the pgaA promoter. These results define a novel mechanism for regulation of biofilm formation in response to environmental conditions and suggest an expanded role for NhaR in promoting bacterial survival.


Vicarious social touch biases gazing at faces and facial emotions.
Research has suggested that interpersonal touch promotes social processing and other-concern, and that women may respond to it more sensitively than men. In this study, we asked whether this phenomenon would extend to third-party observers who experience touch vicariously. In an eye-tracking experiment, participants (N = 64, 32 men and 32 women) viewed prime and target images with the intention of remembering them. Primes comprised line drawings of dyadic interactions with and without touch. Targets comprised two faces shown side-by-side, with one being neutral and the other being happy or sad. Analysis of prime fixations revealed that faces in touch interactions attracted longer gazing than faces in no-touch interactions. In addition, touch enhanced gazing at the area of touch in women but not men. Analysis of target fixations revealed that touch priming increased looking at both faces immediately after target onset, and subsequently, at the emotional face in the pair. Sex differences in target processing were nonsignificant. Together, the present results imply that vicarious touch biases visual attention to faces and promotes emotion sensitivity. In addition, they suggest that, compared with men, women are more aware of tactile exchanges in their environment. As such, vicarious touch appears to share important qualities with actual physical touch. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Brownian escape and force-driven transport through entropic barriers: Particle size effect.
Brownian escape from a spherical cavity through small holes and force-driven transport through periodic spherical cavities for finite-size particles have been investigated by Brownian dynamic simulations and scaling analysis. The mean first passage time and force-driven mobility are obtained as a function of particle diameter a, hole radius R(H), cavity radius R(C), and external field strength. In the absence of external field, the escape rate is proportional to the exit effect, (R(H)R(C))(1-a2R(H))(32). In weak fields, Brownian diffusion is still dominant and the migration is controlled by the exit effect. Therefore, smaller particles migrate faster than larger ones. In this limit the relation between Brownian escape and force-driven transport can be established by the generalized Einstein-Smoluchowski relation. As the field strength is strong enough, the mobility becomes field dependent and grows with increasing field strength. As a result, the size selectivity diminishes.


Sociodemographic And Reproductive Factors Affecting Knowledge Of Married Men Accepting Vasectomy.
Men's attitude is very important in the adoption of methods of contraception and limiting the family size. Men represent half the world's population, but account for less than onethird of contraceptive use. Knowledge of men about vasectomy as contraceptive method is also limited. The objectives of the study were to assess the knowledge of males about vasectomy in age group 25-50 years and to identify the factors affecting the knowledge of men regarding vasectomy. It was cross-sectional descriptive study. All the clients coming for vasectomy at Lahore General Hospital and Family Health Hospital were included in the study. Data was collected through questionnaire, which was entered in to computer using SPSS-17. Confidentiality of the data was ensured and verbal consent was obtained before data collection. Majority (85.6%) of the men had adequate knowledge about vasectomy. Major source of knowledge, motivation and decision making regarding vasectomy were healthcare providers followed by friends and colleagues. Socio-demographic factors like age of the wife, education of men, income of men, media, friends and relatives showed association with knowledge about vasectomy. Almost all the respondents had formal education. Majority of the respondents had knowledge about vasectomy. Respondents acquired knowledge from health personnel, television, radio, newspapers, spouses and friends/colleagues. Misconception of the general population regarding vasectomy needs to be cleared and men should be involved actively in family planning programs. Health education program should be held at community level to educate people about the utilization of procedure.


Prosaposin: a protein with differential sorting and multiple functions.
In eukaryotes the delivery of newly synthesized proteins to their final destination is dependent on a series of functionally distinct compartments, including the endoplasmic reticulum and the Golgi apparatus, which plays a role in post-translational modification, sorting and distribution of proteins. Most cargo is sorted within, and exits from, the trans-Golgi network (TGN). Proteins delivered to lysosomes include hydrolytic enzymes and nonenzymic activator proteins. They are directed away from the cell surface by their binding to mannose-6-phosphate receptors (MPR). However, in I-cell disease, in which the MPR pathway is disrupted, the nonenzymic sphingolipid activator protein, prosaposin, continue to traffic to lysosomes. This observation led to discovery of a new lysosomal sorting receptor, sortilin. The targeting prosaposin to the lysosomes results from the interaction of its C-terminus with sortilin. Deletion of the C-terminus did not interfere with its secretion, but abolished its transport to the lysosomes. Mutational analysis revealed that the first half of the prosaposin C-terminus contains a motif required for its binding to sortilin and its transport to the lysosomes. Prosaposin can be also secreted to the extracellular space as oligomers. Extracellular prosaposin showed to exert a variety of responses in nervous tissues including the activation of G protein-coupled receptors and ERK phosphorylation. Lastly, prosaposin has been found to be expressed in other fluids of the body such as pancreatic juice, bile, cerebrospinal fluid, milk and seminal fluid, indicating that prosaposin is not only a house keeping lysosomal protein but an essential factor in the development and maintenance of the nervous systems and other systems of the body.


Enantioselective binding of albendazole sulphoxide to cytosolic proteins from helminth parasites.
The pharmacological effect of the active albendazole metabolite, albendazole sulphoxide (ABZSO), depends on its sustained presence at the site of parasite location and its binding to helmith beta-tubulin. ABZSO is found in the plasma and tissues of albendazole-treated animals in two enantiomeric forms: (+)ABZSO and (-)ABZSO. Knowledge of enantioselectivity in drug action is necessary, since any difference in target proteins affinity between enantiomers may have implications on the pharmacological effect of this anthelmintic molecule. The binding of ABZSO to mammalian and helminth parasites cytosolic proteins, as well as the differential binding of both enantiomers, were studied. Cytosolic proteins from Moniezia expansa (cestode), Ascaris suum (nematode), Fasciola hepatica (trematode), rat liver and brain as well as purified porcine brain tubulin were used. Drug analysis was performed by HPLC using both C18 and chiral columns. ABZSO protein binding was quantitatively different between parasite species (4.17, 2.5 and 1.07 ng/mg for cestode, nematode and trematode, respectively); this binding to helminth cytosolic proteins was enantioselective. Enantiomeric ratios of (-)ABZSO/(+)ABZSO as a percentage were: 43/57 (Ascaris), 36/64 (Moniezia) and 91/9 (Fasciola). Conversely, the binding of ABZSO to mammalian cytosolic proteins showed no enantioselectivity. The overall binding affinity of ABZSO for mammalian cytosolic proteins was lower than that observed in helminth proteins. The characterization of the comparative binding pattern of ABZSO enantiomers to cytosolic proteins from helminth parasites and mammalian tissues may contribute to understanding the pharmacological properties of this chiral anthelmintic molecule.


Professional skippers' sun-protection knowledge and behavior in the tropics.
A preliminary inquiry, conducted on Martinique Island, sought to determine professional skippers' sun-protection knowledge and behavior. Fifty-two skippers (mean age: 41 years) completed a questionnaire; 39 (75 %) had a simple sunburn over the last 6 months and 3 (6%) severe sunburn; 54 (64%) declared achieving sun protection by wearing clothes during >90% of the day. Only 17% had used sun protection >90% of the time.