Fabrication of zeolite-4A membranes on a catalyst particle level.
Zeolite-4A membranes are coated onto spherical Pt/gamma-Al2O3 particles with an average diameter of 1.5 mm, and a model oxidation reaction of a mixture of CO and n-butane (50 : 50) is used to demonstrate the concept of reactant selectivity via the coated defect-free membranes.


Flexion/extension cervical spine views in blunt cervical trauma.
To examine the contribution of flexion and extension radiographs in the evaluation of ligamentous injury in awake adults with acute blunt cervical spine trauma, who show loss of cervical lordosis and neck pain. All patients who presented to our emergency department following blunt trauma were enrolled in this study, except those with schiwora, neurological deficits or fracture demonstrated on cross-table cervical spine X-rays, and those who were either obtunded or presented after cervical spine surgery. Adequacy of flexion and extension views was checked by the neurosurgery and radiology team members. All these patients underwent cross-table cervical spine view followed by flexion/extension views based on the loss of lordosis on cross-table imaging and the presence of neck pain. A total of 200 cases were reviewed, of whom 90 (45%) underwent repeat X-rays because of either inadequate exposure or limited motion. None of the patients with loss of lordosis on cross-table view had positive flexion and extension views of cervical spine for instability. Our results show that in patients who underwent acute radiographic evaluation of blunt cervical spine trauma, flexion and extension views of the cervical spine are unlikely to yield positive results in the presence of axial neck pain and/or loss of cervical lordosis. We can also hypothesize that performing flexion and extension views will be more useful once the acute neck pain has settled.


Water challenges for the 21st century.
The World Water Council was created in to act as the international water policy think-tank and can thus play a central role in defining the water challenges for the 21 st century and the routes to their solution. This article outlines the origins of the Council and the major steps undertaken since its foundation in 1996, inluding contributions to the various World Water Forums, the World Water Vision and other agenda-setting international meetings.


Zero thermal expansion in NaZn13-type La(Fe,Si)13 compounds.
A zero thermal expansion material in a pure form of NaZn13-type La(Fe,Si)13 was fabricated. Through optimizing the chemical composition, an isotropic zero thermal expansion material is achieved. The obtained materials exhibit a low expansion of |α| < 1.0 × 10(-6) K(-1) (α is the coefficient of linear thermal expansion) over a broad temperature range (15-150 K). The present study indicates that the thermal expansion behavior of the NaZn13-type La(Fe,Si)13 compounds depends mainly on the content of Si element. This new material is desirable in many fields of industry as a reliable and low-cost zero thermal expansion material.


[Results of repeated adenomectomies in high-risk patients].
It is reported on 76 patients who were operated on due to an adenoma of the prostate and simultaneous cystolithiasis. The bilateral adenomectomy of the prostate is justified in geriatric patients who are endangered by a secondary failure of other organ systems. The mortality of this selected number of patients is high in simultaneous adenomectomy with lithotomy despite progress in operation technique, anaesthesiology and treatment with antibiotics. On the other hand, all bilaterally operated patients survived so that we recommend this procedure in all risk patients.


Nanostructure design for drastic reduction of thermal conductivity while preserving high electrical conductivity.
The design and fabrication of nanostructured materials to control both thermal and electrical properties are demonstrated for high-performance thermoelectric conversion. We have focused on silicon (Si) because it is an environmentally friendly and ubiquitous element. High bulk thermal conductivity of Si limits its potential as a thermoelectric material. The thermal conductivity of Si has been reduced by introducing grains, or wires, yet a further reduction is required while retaining a high electrical conductivity. We have designed two different nanostructures for this purpose. One structure is connected Si nanodots (NDs) with the same crystal orientation. The phonons scattering at the interfaces of these NDs occurred and it depended on the ND size. As a result of phonon scattering, the thermal conductivity of this nanostructured material was below/close to the amorphous limit. The other structure is Si films containing epitaxially grown Ge NDs. The Si layer imparted high electrical conductivity, while the Ge NDs served as phonon scattering bodies reducing thermal conductivity drastically. This work gives a methodology for the independent control of electron and phonon transport using nanostructured materials. This can bring the realization of thermoelectric Si-based materials that are compatible with large scale integrated circuit processing technologies.


Performance of a dedicated light delivery and dosimetry device for photodynamic therapy of nasopharyngeal carcinoma: phantom and volunteer experiments.
The objective of this study was to develop a light delivery and measurement device for photodynamic therapy (PDT) in the nasopharyngeal cavity, which achieves a homogeneous and reproducible fluence rate distribution to a target area and provides proper shielding of predefined risk areas. A flexible silicone applicator was developed, incorporating light delivery and dosimetry fibers. The applicator can be inserted through the mouth and fixed in the nasopharyngeal cavity. Tissue optical phantoms were prepared on the basis of optical properties measured in vivo using diffuse reflectance spectroscopy (DRS). The fluence rate over the length of the applicator surface was measured in air, in tissue optical phantoms and in five healthy volunteers. The fluence rate distribution over the applicator surface in air and tissue optical phantom was found to be more homogeneous (SD/mean 3.8% and 18.3%, respectively) than the fluence rate distribution in five volunteers (SD/mean ranging from 19% up to 52%). The maximum observed fluence rate build-up in the nasopharynx varied between subjects and ranged from a factor of 4.1-6.9. Shielding of the risk area such as the soft palate and tongue was effective. In air and in tissue optical phantoms the fluence rate distribution of the device was highly homogeneous. The observed inter-subject and intra-subject variations in fluence rate in healthy volunteers originated from differences in optical properties and nasopharyngeal geometry. Light delivery based on a single tissue surface measurement will not be adequate. In situ dosimetric measurements are required to determine the light fluence delivered to a geometrically complex site such as the nasopharynx. These observations should be taken in consideration when developing light applicators for PDT of the nasopharynx and other non-uniform surfaces.


Migraine and women's health.
Migraine is a significant women's health concern. Epidemiological research has demonstrated that migraine is one of the most common pain conditions and that women are disproportionately affected. Recent advances in pathophysiology highlight the hormonal antecedents of these sex differences in migraine and the potential influence of hormones on migraine pain pathways. Migraine spawns substantial suffering and disability and gives rise to great economic and personal burden. Despite the availability of effective pharmacological and nonpharmacological treatments, only a fraction of migraine sufferers receive state-of-the-art treatment. Access to effective treatment is limited by economic and social barriers to care, including the long-standing social stigma that trivializes headache. Although doubtless a women's health issue, migraine has been largely overlooked in the women's health initiatives. This paper argues that migraine is an important women's health concern and that greater attention to migraine promises to make a demonstrable improvement in the quality of life of many women.


Ethanol exposure impairs LPS-induced pulmonary LIX expression: alveolar epithelial cell dysfunction as a consequence of acute intoxication.
Alcohol intoxication impairs innate immune responses to bacterial pneumonia, including neutrophil influx. Lipopolysaccharide (LPS)-induced chemokine (LIX or CXCL5) is a recently described chemokine produced by type-II alveolar epithelial (AE2) cells which facilitates neutrophil recruitment. The effect of acute alcohol intoxication on AE2 cell expression of LIX is unknown. C57BL/6 mice were given an intraperitoneal (i.p.) injection of ethanol (4 g/kg) or saline 30 minutes prior to intratracheal (i.t.) injection with 10 mug Escherichia coli LPS. In vitro stimulation of primary AE2 cells or murine AE2 cell line MLE-12 was performed with LPS and tumor necrosis factor-alpha (TNF-alpha). LIX protein is readily detectable in the lung but not in plasma following LPS administration, demonstrating "compartmentalization" of this chemokine during pulmonary challenge. In contrast to the CXC chemokines keratinocyte-derived chemokine and macrophage inflammatory protein-2, which are abundantly expressed in both lung tissue and alveolar macrophages, LIX expression is largely confined to the lung parenchyma. Compared to controls, intoxicated animals show a decrease in LIX and neutrophil number in bronchoalveolar lavage fluid following LPS challenge. Ethanol inhibits LIX at the transcriptional level. In vitro studies show that LPS and TNF-alpha are synergistic in inducing LIX by either primary AE2 or MLE-12 cells. Acute ethanol exposure potently and dose-dependently inhibits LIX expression by AE2 cells. Activation of nuclear factor-kappaB is critical to LIX expression in MLE-12 cells, and acute ethanol treatment interferes with early activation of this pathway as evidenced by impairing phosphorylation of p65 (RelA). Inhibition of p38 mitogen-activated protein kinase signaling, but not ERK1/2 activity, in MLE-12 cells by acute alcohol is likely an important cause of decreased LIX expression during challenge. These data demonstrate direct suppression of AE2 cell innate immune function by ethanol and add to our understanding of the mechanisms by which acute intoxication impairs the lung's response to microbial challenge.


MILVA: an interactive tool for the exploration of multidimensional microarray data.
Clustering techniques such as k-means and hierarchical clustering are commonly used to analyze DNA microarray derived gene expression data. However, the interactions between processes underlying the cell activity suggest that the complexity of the microarray data structure may not be fully represented with discrete clustering methods. A newly developed software tool called MILVA (microarray latent visualization and analysis) is presented here to investigate microarray data without separating gene expression profiles into discrete classes. The underpinning of the MILVA software is the two-dimensional topographic representation of multidimensional microarray data. On this basis, the interactive MILVA functions allow a continuous exploration of microarray data driven by the direct supervision of the biologist in detecting activity patterns of co-regulated genes. The MILVA software is freely available. The software and the related documentation can be downloaded from http://www.ncrg.aston.ac.uk/Projects/milva. User 'surrey' as username and '3245' as password to login. The software is currently available for Windows platform only.


Locomotor-related networks in the lumbosacral enlargement of the adult spinal cat: activation through intraspinal microstimulation.
It is commonly accepted that locomotor-related neuronal circuitry resides in the lumbosacral spinal cord. Pharmacological agents, epidural electrical stimulation, and sensory stimulation can be used to activate these instrinsic networks in in vitro neonatal rat and in vivo cat preparations. In this study, we investigated the use of low-level tonic intraspinal microstimulation (ISMS) as a means of activating spinal locomotor networks in adult cats with complete spinal transections. Trains of low-amplitude electrical pulses were delivered to the spinal cord via groups of fine microwires implanted in the ventral horns of the lumbosacral enlargement. In contrast to published reports, tonic ISMS applied through microwires in the caudal regions of the lumbosacral enlargement (L7-S1) was more effective in eliciting alternating movements in the hindlimbs than stimulation in the rostral regions. Possible mechanisms of action of tonic ISMS include depolarization of locally oscillating networks in the lumbosacral cord, backfiring of primary afferents, or activation of propriospinal neurons.


Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications.
Intraductal papillary mucinous neoplasms (IPMNs) are increasingly recognized entities, whose management remains sometimes controversial, due to the high rate of benign lesions and on the other side to the good survival after resection of malignant ones. Retrospective analysis of a prospectively collected Western series of IPMN. Forty cases of IPMN were analysed (1992-2007). Most patients were symptomatic (72.5%); cholangio-MRI had the best diagnostic accuracy both for the tumour nature (83.3%) and for the presence of malignancy (57.1%). ERCP was done in 8 cases (20%), and the results were poor. Thirteen patients were treated by pancreatic resection and 27 were maintained in follow-up. Total pancreatectomy was performed in 46% of the cases; in situ and invasive carcinoma were recognized in 15.4% and 38.4% of the cases, respectively. The mean follow-up was 42 months (range 12-72). One only patients with nodal metastases died 16 months after the operation for disease progression, while 91.6% of the operated patients are disease free. Out of the 27 not resected patients, 2 out of 4 presenting a lesion at high risk for malignancy died, while the remaining are in good conditions and disease free, with a mean follow-up of 31 months. Therapeutic indication for IPMNs is mainly based upon radiological evaluation of the risk of malignancy. While the main duct tumours should be resected, preserving whenever possible a portion of the gland, the secondary ducts tumours may be maintained under observation, in absence of radiological elements of suspicion such as size larger than 3 cm, or a wall greater than 3 mm or nodules or papillae in the context of the cyst.


Effect of Reducing the Size and Number of Faces of Polyhedral Specimen on Wood Characterization by Ultrasound.
The complete characterization of wood, with the determination of the 12 elastic constants that represent its orthotropy, is greatly relevant in applications employing structural calculation software programs. Ultrasound allows for such characterization with relative simplicity when compared to other methods. The polyhedron is considered the most appropriate specimen format for allowing the 12 constants to be calculated with a single specimen, and the traditionally used one is the 26-sided polyhedron, which, to be produced manually with more precision in directing the main directions of the wood, needs larger faces. The accuracy of this technique tends to be reduced when increasing the growth rings' inclination since the waves deviate from the main directions of orthotropy. This research aimed to verify whether it is possible to reduce the polyhedra dimension without affecting the results of the elastic parameters obtained in wood characterization by ultrasound. The results indicate that the dimension of the polyhedron can be reduced without prejudice to the results of the elastic parameters obtained by the ultrasound test and that, in the manual production process of the specimen, the best way to make this reduction is to eliminate the faces unused in the test, changing the polyhedron to 18 faces instead of 26. Reducing the number of faces simplifies the manufacturing process and thus increases the possibility of producing specimens with straighter growth rings and better-directed symmetry axes.


High-Quality Draft Genome Sequence of Lactobacillus casei Strain Z11, Isolated from a Human Adult Intestinal Biopsy Sample.
Several Lactobacillus casei strains are used as probiotics. L. casei strain Z11, isolated from a human colon biopsy sample, has been suggested as a probiotic candidate based on promising properties in vitro Here, we present a 2.74-Mbp high-quality draft genome sequence for this strain.


Synthesis of novel selenapenams, selenacephems, and selenazepines using a 2-(trimethylsilyl)ethyl protection approach.
Selenapenams, selenacephems, and selenazepines were synthesized using a 2-(trimethylsilyl)ethyl (TSE) protection approach in an extremely simple way. TSE protection for selenium is used for the first time in the synthesis of selenium-containing beta-lactam. Novel intramolecular cycloaddition reaction of selenium with alkynes and allenes is used in the present synthesis.


Discretization of gene expression data revised.
Gene expression measurements represent the most important source of biological data used to unveil the interaction and functionality of genes. In this regard, several data mining and machine learning algorithms have been proposed that require, in a number of cases, some kind of data discretization to perform the inference. Selection of an appropriate discretization process has a major impact on the design and outcome of the inference algorithms, as there are a number of relevant issues that need to be considered. This study presents a revision of the current state-of-the-art discretization techniques, together with the key subjects that need to be considered when designing or selecting a discretization approach for gene expression data.


Efferent Mechanisms of Discharging Cnidae: II. A Nematocyst Release Response in the Sea Anemone Tentacle.
Feeding behavior in cnidarians is a sequence of coordinated responses beginning with nematocyst discharge. The nematocyst response produces prey capture by envenomating prey and attaching prey to the tentacle. The strength of attachment of discharged nematocysts to the tentacle is termed intrinsic adherence and is calculated from measurements of adhesive force. Following prey capture, the feeding response involves movement of the tentacles toward the mouth and mouth opening. For ingestion to occur, nematocysts attaching the prey to the tentacles must be released from the tentacle. A nematocyst release response has been proposed, but never documented nor measured. Our criterion for a nematocyst release response is that the intrinsic adherence of discharged nematocysts must decrease to zero. The unit of nematocyst discharge in sea anemone tentacles is the cnidocyte/ supporting cell complex (CSCC). The nematocyst response includes nematocysts discharged from Type C CSCCs by physical contact alone and nematocysts discharged from the more numerous Type B CSCCs that require both chemosensitization and physical contact. We identify two prey-derived substances, N-acetylneuraminic acid (NANA) and glycine, both of which chemosensitize nematocyst discharge from Type B CSCCs at low concentrations. At higher concentrations NANA stimulates the release response of Type Cs, and glycine stimulates the release response of Type Bs.


Comparison between two chromogenic substrates for revealing an immunoperoxidase reaction of human metaphase chromosomes.
To study the binding of an antiadenosine serum to human chromosome DNA, two types of chromogenic reagents were compared. The procedure is as follows: lymphocytes with metaphase chromosomes were spread on slides; some slides were irradiated by UV; all slides were then incubated with antiadenosine rabbit serum and then with antirabbit sheep serum labelled with peroxidase; the latter was revealed in the classical manner by 3,3'-diaminobenzidine (DAB), or, alternatively, by p-phenylenediamine plus pyrocatechol (PPD-PC). The present study shows that the results obtained with PPD-PC were equivalent, if not superior, to those obtained with DAB. In the case of weaker reactions, results with PPD-PC were superior. Furthermore, this reagent has the major advantage of being noncarcinogenic.


Pharmacogenetic prediction of individual variability in drug response based on CYP2D6, CYP2C9 and CYP2C19 genetic polymorphisms.
Interindividual variability in drug response depends on a number of genetic and environmental factors. The metabolic enzymes are well known for their contribution to this variability due to drug-drug interactions and genetic polymorphisms. The phase I drug metabolism is highly dependent upon the cytochrome P450 mono-oxygenases (CYP) and their genetic polymorphism leads to the variable internal drug exposures. The highly polymorphic CYP2C9, CYP2C19 and CYP2D6 isozymes are responsible for metabolizing a large portion of routinely prescribed drugs and contribute significantly to adverse drug reactions and therapeutic failures. In this review, two attractive and easily implementable approaches are highlighted to recommend drug doses ensuring similar internal exposures in the face of these polymorphisms. The first approach relies on subpopulation-based dose recommendations that consider the original population dose as an average of the doses recommended in genetically polymorphic subpopulations. By using bioequivalence principles and assuming linear gene-dose effect, dose recommendations can be made for different metabolic phenotypes. The second approach relates area under the curve to two characteristic parameters; the contribution ratio (CR), computes for the contribution of the metabolic enzyme and the fractional activity (FA), considers the impact of the genetic polymorphism. This approach provides valid and error free internal drug exposure predictions and can take into consideration genetic polymorphisms and drug interactions and/ or both simultaneously. Despite certain advantages and limitations, both approaches provide a good initial frame-work for devising models to predict internal exposure and individualize drug therapy, one of the promises from human genome project.


Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial.
The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib. Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib. Twenty patients (median age: 14 years) were treated. All were evaluable for response and toxicities. The most frequent diagnoses were high-grade glioma (HGG; n = 7) and rhabdomyosarcoma (n = 7). Twenty-one actionable mutations were detected: hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), inactivating mutations in NF1 (n = 7), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease including two patients with HGG (NF1 mutation, six cycles; KRAS mutation, 12 cycles). Six-month progression-free survival was 15% (95% CI, 4 to 34). Five patients (25%) experienced a grade 3 or higher adverse event that was possibly or probably attributable to study drug. A national histology-agnostic molecular screening strategy was effective at identifying children and young adults eligible for treatment with selumetinib in the first Pediatric MATCH treatment arm to be completed. MEK inhibitors have demonstrated promising responses in some pediatric tumors (eg, low-grade glioma and plexiform neurofibroma). However, selumetinib in this cohort with treatment-refractory tumors harboring MAPK alterations demonstrated limited efficacy, indicating that pathway mutation status alone is insufficient to predict response to selumetinib monotherapy for pediatric cancers.


[Mass accident and catastrophe medicine].
Medical management of mass casualties and catastrophy are discussed and principles of treatment outlined, consisting in first aid, improvisation, sorting (triage), organised help and avoiding panic and epidemics. Preparedness and leadership, summarised under the heading "catastrophy planning" are the most important elements to counteract catastrophies.


[Strategies of vaccination for adult population in Spain in the actuality].
The introduction of vaccines around the world has avoided millions of deaths among children and adults every year. Taking into account that some vaccines administered in the childhood do not lend long term immunity, unless a booster dose is given, vaccinated subjects return susceptible with the course of time. Implementation of vaccination policies and recommendations to adult population is important in order to complement vaccination childhood programs and intensify its impact in the infection control.


Clear-cell syringoma. Association with diabetes mellitus.
Only one case of clear-cell syringoma has been reported in the United States, whereas six cases have already been reported in Japan, and ours described herein constitute an eighth and ninth. Eight of the total of nine cases of clear-cell syringoma were associated with diabetes mellitus. In this report, we summarize these nine cases and emphasize the close relationship between clear-cell syringoma and diabetes mellitus.


Suppression of adrenomedullin contributes to vascular leakage and altered epithelial repair during asthma.
The anti-inflammatory peptide, adrenomedullin (AM), and its cognate receptor are expressed in lung tissue, but its pathophysiological significance in airway inflammation is unknown. This study investigated whether allergen-induced airway inflammation involves an impaired local AM response. Airway AM expression was measured in acute and chronically sensitized mice following allergen inhalation and in airway epithelial cells of asthmatic and nonasthmatic patients. The effects of AM on experimental allergen-induced airway inflammation and of AM on lung epithelial repair in vitro were investigated. Adrenomedullin mRNA levels were significantly (P < 0.05) reduced in acute ovalbumin (OVA)-sensitized mice after OVA challenge, by over 60% at 24 h and for up to 6 days. Similarly, reduced AM expression was observed in two models of chronic allergen-induced inflammation, OVA- and house dust mite-sensitized mice. The reduced AM expression was restricted to airway epithelial and endothelial cells, while AM expression in alveolar macrophages was unaltered. Intranasal AM completely attenuated the OVA-induced airway hyperresponsiveness and mucosal plasma leakage but had no effect on inflammatory cells or cytokines. The effects of inhaled AM were reversed by pre-inhalation of the putative AM receptor antagonist, AM ((22-52)) . AM mRNA levels were significantly (P < 0.05) lower in human asthmatic airway epithelial samples than in nonasthmatic controls. In vitro, AM dose-dependently (10(-11) -10(-7) M) accelerated experimental wound healing in human and mouse lung epithelial cell monolayers and stimulated epithelial cell migration. Adrenomedullin suppression in T(H) 2-related inflammation is of pathophysiological significance and represents loss of a factor that maintains tissue integrity during inflammation.


[2,3]-Wittig Rearrangement as a Formal Asymmetric Alkylation of α-Branched Ketones.
The enantioselective [2,3]-Wittig rearrangement of cinnamyloxycyclopentanone derivatives was performed in the presence of a Cinchona-based primary amine. The described method provides synthetically valuable α-hydroxy ketones with quaternary stereogenic centers in excellent enantiomeric purities. Relying on the X-ray crystal structure of the product and the DFT calculations, we propose that the rearrangement is promoted by an intramolecular hydrogen bond between the substrate and the catalyst.


Development from Jasminum sambac Flower Extracts of Products with Floral Fragrance and Multiple Physiological Activities.
To obtain a potential commercial product with floral fragrance and physiological properties from Jasminum sambac flower extracts, enfleurage was conducted for a short time and followed by further extraction through supercritical fluid extraction (SFE). The product extracted through SFE (called 100%SFE) exhibited low physiological activity (including 50.7% antityrosinase activity, 38.6%-45.9% radical scavenging activity, and 6,518-15,003 mg/L half-maximal inhibitory concentration [IC50] of antioxidant activity) and an intense jasmine-like flavor but was nontoxic to CCD-996SK and HEMn cells. By contrast, the residue (called RO) exhibited high physiological activity (94.2%-100%), light jasmine-like flavor, and slight cytotoxicity at the concentration of 4,000 mg/L. When 100%SFE and RO were mixed in the ratio 2 : 8, the resultant mixture exhibited 100% antityrosinase activity, >91.3% radical scavenging activity, strong antioxidant activity (IC50: 273-421 mg/L), high total phenolic content (172.15 mg-GAE/g-extract), noncytotoxicity, and moderately intense jasmine-like flavor; it is also economically competitive. The major antioxidants in these extracts were revealed through gas chromatography-mass spectroscopy (GC-MS). Additionally, the composition and quality of fragrance were confirmed through GC-MS and sensory evaluation, respectively. The major fragrance components in the 2 : 8 extract mixture were benzyl acetate, β-pinene, pentadecyl-2-propyl ester, citronellol, jasminolactone, linalool, farnesol, and jasmone. On the basis of the results, we strongly suggest that the 2 : 8 mixture of extracts from J. sambac flowers can be a powerful antioxidant, whitening, and nontoxic ingredient that can be employed in the pharmaceutical, cosmeceutical, and food industries.


Angiotensin II Type 2 Receptor Inhibits Vascular Intimal Proliferation With Activation of PPARγ.
Angiotensin II type 2 (AT2) receptor stimulation could exert beneficial effects on vascular remodeling. Previously, we reported that AT2 receptor stimulation ameliorated insulin resistance in diabetic mice accompanied by PPARγ activation which also plays a variety of crucial roles in the vasculature. Therefore, this study aimed to investigate the vascular protective effect of the AT2 receptor with activation of PPARγ involving AT2 receptor-interacting protein (ATIP). Vascular injury was induced by polyethylene-cuff placement around the femoral artery in C57BL/6J mice. Treatment with compound 21 (C21), an AT2 receptor agonist, decreased neointimal formation, cell proliferation, and the mRNA levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and interleukin-1β, and phosphorylation of nuclear factor-kappa B, and increased PPARγ DNA-binding activity in the injured artery, whereas these inhibitory effects of C21 were attenuated by co-treatment with a PPARγ antagonist, GW9662. Treatment of vascular smooth muscle cells (VSMC) with C21 prepared from smAT2 transgenic mice, which highly express the AT2 receptor in VSMC, increased both PPARγ activity and its DNA-binding activity determined by dual-luciferase assay and electrophoresis mobility shift assay (EMSA), respectively. We observed that ATIP was involved in PPARγ complex formation, and that transfection of siRNA of ATIP1 attenuated the AT2 receptor-mediated increase in PPARγ activity in VSMC. In response to AT2 receptor stimulation, ATIP was translocated from the plasma membrane to the nucleus. Our results suggest a new mechanism by which AT2 receptor stimulation activates PPARγ, thereby resulting in amelioration of vascular intimal proliferation, and that ATIP plays an important role in AT2 receptor-mediated PPARγ activation.


The Unfolded State of the C-Terminal Domain of L9 Expands at Low but Not at Elevated Temperatures.
The temperature dependence of the overall dimensions of the denatured state ensemble (DSE) of proteins remains unclear. Some studies indicate compaction of the DSE at high temperatures, whereas others argue that dimensions do not decrease. The degree of compaction or expansion in the cold-denatured state has been less studied. To investigate the temperature dependence of unfolded state dimensions, small angle x-ray scattering measurements were performed in native buffer in the absence of denaturant for a designed point mutant of the C-terminal domain of L9, a small cooperatively folded α-β protein, at 14 different temperatures over the range of 5-60°C. The I98A mutation destabilizes the domain such that both the DSE and the folded state are populated at 25°C in the absence of denaturant or extreme pH. Thermal unfolding as well as cold unfolding can thus be observed in the absence of denaturant, allowing a direct comparison of these regimes for the same protein using the same technique. The temperature of maximal stability, Ts, is 30°C. There is no detectable change in Rg of the unfolded state as the temperature is increased above Ts, but a clear expansion is detected as the temperature is decreased below Ts. The Rg of the DSE populated in buffer was found to be 27.8 ± 1.7 Å at 5°C, 21.8 ± 1.9 Å at 30°C, and 21.7 ± 2.0 Å at 60°C. In contrast, no significant temperature dependence was observed for the value of Rg measured in 6 M guanidine hydrochloride. The small angle x-ray scattering data reported here indicate clear differences between the cold- and thermal-unfolded states and show that there is no significant compaction at elevated temperatures.


Multidrug resistance-associated protein 7 expression is involved in cross-resistance to docetaxel in salivary gland adenocarcinoma cell lines.
The aim of the present study was to clarify whether ATP binding cassette transporters are refractory factors in head and neck cancers. For in vitro and in vivo chemotherapeutic studies, we used the following head and neck cancer cell lines: a mouse oral squamous cell carcinoma (SCC) cell line, Sq-1979; a human SCC cell line, SCCHA; a mouse salivary gland adenocarcinoma (SGA) cell line, NR-PG; and a human SGA cell line, HSY. We used a vinca alkaloid anticancer drug, vincristine (VCR), as a chemotherapeutic anticancer drug. To determine the cause of multidrug resistance, Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry of xenografted tumors in nude mice, drug efflux analysis, and drug efflux inhibitory assays were performed. VCR-treated cell lines, Sq-1979/VCR, SCCHA/VCR, NR-PG/VCR, and HSY/VCR, intensively expressed multidrug resistance (MDR) gene 1 mRNA and multidrug resistance associated protein (MRP) 1 mRNA. MRP7 mRNA and protein were expressed in NR-PG/VCR and HSY/VCR cells, but not in Sq-1979/VCR and SCCHA/VCR cells. In each cell clone of NR-PG/VCR and HSY/VCR, MRP7 mRNA was induced by VCR treatment, suggesting an acquired resistance to VCR in the context of MRP7 expression. In the in vivo chemotherapeutic nude mice model, VCR-treated xenografted SCCHA and HSY cells expressed MDR1 and MRP1. Moreover, MRP7 expression was immunohistochemically found in xenografted HSY cells of VCR-injected tumor-bearing mice, but not in SCCHA cells. Furthermore, doxorubicin accumulation was increased and drug cross-resistance to docetaxel decreased in HSY/VCR in the presence of a competitive MRP7 inhibitor, 17-beta-estradiol-(17-beta-D-glucuronide). These results indicate that MDR1 expression, MRP1 expression, and MRP7 expression are refractory factors in head and neck cancer chemotherapy and suggest that induction of MRP7 expression is involved in drug resistance to natural products, especially to docetaxel in SGA.


An IC-PLS framework for group corticomuscular coupling analysis.
Corticomuscular coupling analysis, i.e., examining the relations between simultaneously recorded brain (e.g., electroencephalography--EEG) and muscle (e.g., electro-myography-EMG) signals, is a useful tool for understanding aspects of human motor control. Traditionally, the most popular method to assess corticomuscular coupling has been the pairwise magnitude-squared coherence (MSC) between EEG and concomitant EMG recordings. In this paper, we propose assessing corticomuscular coupling by combining partial least squares (PLS) and independent component analysis (ICA), which addresses many of the limitations of MSC, such as difficulty in robustly assessing group inference and relying on the biologically implausible assumption of pairwise interaction between brain and muscle recordings. In the proposed framework, response relevance and statistical independence are jointly incorporated into a multiobjective optimization function to meaningfully combine the goals of PLS and ICA under the same mathematical umbrella. Simulations, performed under realistic assumptions, illustrated the utility of such an approach. The method was extended to address intersubject variability to robustly discover common corticomuscular coupling patterns across subjects. We then applied the proposed framework to concurrent EEG and EMG data collected in a Parkinson's disease (PD) study. The results from applying the proposed technique revealed temporal components in the EEG and EMG that were significantly correlated with one another. In addition to the expected motor areas, the corresponding spatial activation patterns demonstrated enhanced occipital connectivity in PD subjects, consistent with previous studies suggesting that PD subjects rely excessively on visual information to counteract the deficiency in being able to generate internal commands from their affected basal ganglia.


Association analysis of polymorphisms in ROCK2 with cardiovascular disease in a Chinese population.
Rho-kinase (ROCK) has been shown to play an important role in cardiovascular disease such as coronary artery disease (CAD) and hypertension. Recently, common variants of ROCK2 have been reported to influence blood pressure, but the relationship between common ROCK2 variants and cardiovascular disease has not been extensively studied in the Chinese population. To derive a more precise estimation of their relationship, we screened for the common variants by direct sequencing of all exons of ROCK2, and then we performed genetic association analyses in a CAD case-control study, including a total of 1344 cases and 1267 ethnically and geographically matched controls. Unconditional logistic regression showed that no significant association between common variants in the coding region of ROCK2 and CAD was observed in our study (for rs978906, OR = 0.92, 95% CI 0.72-1.20 and P = 0.63; for rs2230774, OR = 0.90, 95% CI 0.70-1.16 and P = 0.47; for rs56304104, OR = 0.97, 95% CI 0.70-1.31 and P = 0.83; respectively). The relationship between the ROCK2 polymorphisms and cardiovascular disease risk cannot be entirely discounted and warrants further evaluation in a large population.


Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method.
To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.


Propylthiouracil-related hemorrhagic diathesis: a case report and review of the literature.
We present an unusual case of a drug-related hemorrhagic diathesis. One month prior to admission, the patient was diagnosed at another medical center as having Graves' disease and propylthiouracil therapy (PTU) was initiated. Since clinical recovery was not achieved, the PTU was quickly increased to an unconventional daily dose of 1,000 mg. The patient was referred to our hospital because of spontaneous epistaxis, multiple ecchymoses and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), which developed soon after the increase in PTU dose. Drug-related hemorrhagic diathesis was considered, after other possible causes had been eliminated. To the best of our knowledge, this is the first reported case of spontaneous hemorrhage due to PTU use.


In vitro blood damage by high shear flow: human versus porcine blood.
Devices for modern heart support are minimized to reduce priming blood volume and contact area with foreign surfaces. Their flow fields are partly governed by very high velocity gradients. In order to investigate blood damage, porcine and human blood was passed through a narrow Couette type shear gap applying defined high shear rates within the typical range for devices such as blood pumps or artificial heart valves (gamma = 1800/s to 110,000/s for 400 ms). Traumatization profiles of both blood species were recorded in terms of hemolysis and platelet count. Sublethal damage in terms of platelet (PF4) and complement activation (C5a) was additionally measured for human blood. Results for porcine and human blood were very similar. Hemolysis was not started until critical shear rates of about 80,000/s. Impact on platelets was severe with drops in cell count of up to 65% (at gamma = 55,000/s to 110,000/s) likely to set stronger limits to the design layout of devices than hemolysis. Concentrations of PF4 and C5a clearly increased with shear rate exhibiting stronger gradients where hemolysis started. Due to the similar results of porcine and human blood for hemolysis and platelet drop, porcine blood seems to be suitable for device testing. Selection of blood species would thus depend on handling, availability and analysis demands.


Nonlinear dynamics of membrane skeleton in osteocyte.
Osteocytes play an important role in mechanosensation and conduction in bone tissue, and the change of mechanical environment can affect the sensitivity of osteocytes to external stimulation. The structure of osteocytes will be changed when they are subjected to vibrations, which influence the mechanosensitivity of osteocytes and alter the regulation of bone remodeling process. As an important mechanotransduction structure in osteocytes, the membrane skeleton greatly affects the mechanosensation and conduction of osteocytes. However, the dynamic responses of membrane skeleton to the vibration and the structural changes of membrane skeleton are unclear. Therefore, we applied a nonlinear dynamics method to explain the time-dependent changes of membrane skeleton. The semi-ellipsoidal reticulate shell structure of membrane skeleton is built based on the experimental observation in our previous work. Then, the nonlinear dynamic equations of membrane skeleton are established according to the theory of plate and shell dynamics, and the displacement-time curves, phase portraits, and Poincaré maps of membrane skeleton structure were obtained. The numeration results show that under the vibration stimulation of 15 Hz, 30 Hz, 60 Hz, and 90 Hz, the membrane skeleton is destroyed after a transient equilibrium position vibration. The vibration of 15 Hz has the most destructive effect on the membrane skeleton, the natural frequency of membrane skeleton may be less than 15 Hz. In addition, the chaos phenomenon occurs to the membrane skeleton during vibration. As a damping factor, the existence of viscosity alleviates the damage of structure. This study can help us to understand the oscillation characteristic of membrane skeleton in osteocyte.


Prospective Analysis of Immunosuppressive Therapy in Cardiac Sarcoidosis With Fluorodeoxyglucose Myocardial Accumulation: PRESTIGE Study.
Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) can noninvasively assess active inflammatory myocardium in patients with cardiac sarcoidosis (CS). Prednisolone (PSL) is the initial drug of choice for active CS; however, its efficacy has not been prospectively evaluated. Moreover, there are no alternative systematic treatment strategies. The goal of this study was to evaluate the efficacy of methotrexate (MTX) in patients refractory to PSL assessed by using cardiac metabolic activity (CMA) in 18F-FDG-PET. A total of 59 patients with active CS were prospectively enrolled. CMA (standardized uptake value × accumulation area) was used as an indicator of active inflammation, and a 6-month regimen of PSL therapy was introduced, followed by a second FDG scan. Poor responders to PSL therapy (CMA reduction rate <70%) and patients with recurrent CS (CMA reduction rate ≥70% after initial PSL therapy but CMA recurred after an additional 6 months of therapy) were randomly assigned to the MTX or repeat PSL (re-PSL) therapy groups for another 6 months. Fifty-six patients completed the initial 6-month PSL therapy regimen. Median CMA reduced from 203.3 to 1.0 (P < 0.001), and 47 patients were allocated to the response group, 9 to the poor response group, and 2 to the recurrent group. Accordingly, 11 patients were randomly assigned to the MTX (n = 5) or re-PSL (n = 6) groups. After 6 months, neither group showed a significant reduction in CMA values. MTX was comparable to re-PSL in reducing CMA. The 6-month regimen of PSL was a potent therapeutic tool for active CS. When MTX was added to low-dose PSL in patients refractory to the initial PSL therapy, there was no significant difference compared with re-PSL. Further studies are needed to evaluate the therapeutic potential of MTX for active CS, including how MTX works when it is administered in higher doses or for longer periods.


Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension.
We performed an open-label multicenter study to evaluate the safety and efficacy of the dual endothelin receptor antagonist bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Nineteen patients with inoperable CTEPH were enrolled. The primary end point was a change in pulmonary vascular resistance (PVR). Secondary end points included 6-min walk test, peak oxygen uptake (V(O2)), New York Heart Association functional class, serum levels of N-terminal-pro brain natriuretic peptide (NT-pro-BNP), and various other hemodynamic parameters. After 3 months of treatment with bosentan, PVR decreased from 914 +/- 329 to 611 +/- 220 dyne.s.cm(-5) (p < 0.001). Functional class and peak V(O2) remained unchanged, but 6-min walk distance increased from 340 +/- 102 to 413 +/- 130 m (p = 0.009), and serum NT-pro BNP levels improved from 2,895 +/- 2,620 to 2,179 +/- 2,301 (p = 0.027). One patient died, presumably from influenza A infection, and another patient experienced progressive fluid retention despite reduction of PVR. Other than that, treatment was well tolerated by all patients. This open-label pilot trial suggests that bosentan may offer a therapeutic option for patients with inoperable CTEPH. Randomized controlled trials are warranted to confirm these findings.


A comprehensive guidelines-based approach reduces cardiovascular risk in everyday practice: the VARO study.
The aim of study was to investigate the possibility of cardiovascular risk improvement through systematic identification of high-risk individuals and treatment in accordance with current guidelines using modern therapy in daily clinical practice. Two hundred and sixty-three physicians participated in the study. The physicians were asked to screen for cardiovascular risk factors in patients presenting with unrelated problems and to re-evaluate the attainment of treatment goals in those with already known risk factors. Each physician enrolled up to 20 consecutive patients with hypertension and/or hyperlipidemia. A total of 3015 patients were included. Cardiovascular risk was assessed using the SCORE system. Risk factors were treated in accordance with current national guidelines. The therapy of hyperlipidemia and hypertension was preferentially based on rosuvastatin, amlodipine and valsartan. Further medication was at the discretion of the attending physician. Patients were examined at baseline and after 3 and 6 months. The principal result is that global cardiovascular risk decreased by 35% (from 8.9 ±6.4 to 5.9 ±4.4, p < 0.001). Systolic and diastolic blood pressure decreased by 12.5% (from 152 ±18 to 133 ±11, p < 0.001) and 11.4% (from 88 ±11 to 78 ±7, p < 0.001). The level of total cholesterol decreased 21% (from 6.3 ±1.2 to 5.0 ±0.9, p < 0.001) and the concentration of LDL-C decreased 28% (from 3.9 ±1.1 to 2.8 ±0.8, p < 0.001). HDL-C increased by 7% (from 1.43 ±0.58 to 1.53 ±0.56, p < 0.001) and triglycerides decreased by 25% (from 2.4 ±1.3 to 1.8 ±0.9, p < 0.001). Blood pressure and LDL-C target values were reached in 68% and 34%of patients, respectively. The VARO study demonstrates that in daily practice settings, both individual risk factors and global cardiovascular risk are significantly improved through the systematic identification of high-risk individuals and their treatment in accordance with current guidelines using modern pharmacotherapy.


Structure Zone Investigation of Multiple Principle Element Alloy Thin Films as Optimization for Nanoindentation Measurements.
Multiple principal element alloys, also often referred to as compositionally complex alloys or high entropy alloys, present extreme challenges to characterize. They show a vast, multidimensional composition space that merits detailed investigation and optimization to identify compositions and to map the composition ranges where useful properties are maintained. Combinatorial thin film material libraries are a cost-effective and efficient way to create directly comparable, controlled composition variations. Characterizing them comes with its own challenges, including the need for high-speed, automated measurements of dozens to hundreds or more compositions to be screened. By selecting an appropriate thin film morphology through predictable control of critical deposition parameters, representative measured values can be obtained with less scatter, i.e., requiring fewer measurement repetitions for each particular composition. In the present study, equiatomic CoCrFeNi was grown by magnetron sputtering in different locations in the structure zone diagram applied to multinary element alloys, followed by microstructural and morphological characterizations. Increasing the energy input to the deposition process by increased temperature and adding high-power impulse magnetron sputtering (HiPIMS) plasma generators led to denser, more homogeneous morphologies with smoother surfaces until recrystallization and grain boundary grooving began. Growth at 300 °C, even without the extra particle energy input of HiPIMS generators, led to consistently repeatable nanoindentation load-displacement curves and the resulting hardness and Young's modulus values.


Performance of Homeostatic Controller Motifs Dealing with Perturbations of Rapid Growth and Depletion.
An essential property of life is that cells and organisms have the ability to protect themselves against external disturbances/attacks by using homeostatic mechanisms. These defending mechanisms are based on negative feedback regulation and often contain additional features, such as integral control, where the integrated error between a controlled variable and its set-point is used to achieve homeostasis. Although the concept of integral control has its origin in industrial processes, recent findings suggest that biological systems are also capable of showing integral control. We recently described a basic set of negative feedback structures (controller motifs) where robust homeostasis is achieved against different but constant perturbations. As many perturbations in biology, such as infections, increase rapidly over time, we investigated how the different controller motifs equipped with different implementations of integral control perform in relation to rapidly changing perturbations, including exponential and hyperbolic changes. The findings show that the construction of an optimum biochemical controller design for time-dependent perturbations requires a certain match between the structure of the negative feedback loop, its signaling kinetics, and the kinetics of how integral control is implemented within the negative feedback loop.


Judging scandal: Standards or bias in politics.
As the number of political scandals rises, we examined the circumstances that might influence how a politician would be judged as a result of a scandal. Specifically, we hypothesized that ingroup bias theory and shifting standards theory would produce different patterns of judgements. In two studies, we found support for the ingroup bias theory, such that participants rated the fictitious politician's public approval and perceived character as higher if the politician was a member of their own political party (i.e. their ingroup) than if the politician was a member of the another political party (i.e. their outgroup). These results may explain, in part, why people may judge politicians involved in scandal more or less harshly depending on whether they are an ingroup member or outgroup member.


Influenza viruses and the evolution of avian influenza virus H5N1.
Although small in size and simple in structure, influenza viruses are sophisticated organisms with highly mutagenic genomes and wide antigenic diversity. They are species-specific organisms. Mutation and reassortment have resulted in newer viruses such as H5N1, with new resistance against anti-viral medications, and this might lead to the emergence of a fully transmissible strain, as occurred in the 1957 and 1968 pandemics. Influenza viruses are no longer just a cause of self-limited upper respiratory tract infections; the H5N1 avian influenza virus can cause severe human infection with a mortality rate exceeding 50%. The case death rate of H5N1 avian influenza infection is 20 times higher than that of the 1918 infection (50% versus 2.5%), which killed 675000 people in the USA and almost 40 million people worldwide. While the clock is still ticking towards what seems to be inevitable pandemic influenza, on April 17, 2007 the U.S. Food and Drug Administration (FDA) approved the first vaccine against the avian influenza virus H5N1 for humans at high risk. However, more research is needed to develop a more effective and affordable vaccine that can be given at lower doses.


Bovine C4b binding protein. Molecular cloning of the alpha- and beta-chains provides structural background for lack of complex formation with protein S.
C4b binding protein (C4BP) regulates the complement system. It also interacts with anticoagulant protein S and with serum amyloid P component. Human C4BP is composed of seven identical 70-kDa alpha-chains and one 45-kDa beta-chain. The binding site for C4b is located on the alpha-chain, whereas the beta-chain binds protein S. Nothing is known about the structure and function of bovine C4BP. No complexed form of protein S was detected by using a gel filtration chromatography system combined with Western blotting. Bovine cDNA clones encoding the C4BP alpha- and beta-chains were isolated from a bovine liver cDNA library. Three overlapping alpha-chain clones predicted a 562-amino acid residues-long mature polypeptide. The overall amino acid sequence similarity with the human alpha-chain was 61%. Like its human counterpart, the bovine alpha-chain is composed of eight contiguous short consensus repeat units, each of approximately 60 amino acid residues, and a carboxyl-terminal nonrepeat region. One bovine beta-chain clone was found and characterized. It predicted a mature bovine beta-chain of 181 amino acid residues. The identity with the human beta-chain was 65% at the amino acid level. A noteworthy difference between bovine and human beta-chains was that the bovine beta-chain only contained two short consensus repeats compared with three in human beta-chain. Sequence alignment indicates that the region corresponding to residues 1-60 (repeat 1) in the human beta-chain is absent in the homologous bovine polypeptide. Because the short consensus repeats of the human beta-chain contain the binding site for protein S, the lack of one repeat unit in the bovine beta-chain may provide a clue to the lack of complex formation between C4BP and protein S in bovine plasma.


Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy.
To evaluate the virological outcomes in children and adolescents infected with HIV-1 in Salvador, Bahia according to genotyping results. We retrospectively evaluated the rates of virological suppression of children and adolescents submitted to HIV-1 genotyping test from January/2008 to December/2012. The participants were followed in the two referral centers for pediatric AIDS care, in Salvador, Brazil. Resistance mutations, drug sensitivity profiles, and viral subtypes were analyzed using the Stanford HIV-1 Drug Resistance Database. Adherence was estimated by drugs withdrawal at pharmacies of the two sites. 101 subjects were included: 35 (34.6%) were drug-naïve, and the remaining 66 were failing ART. In drug-naïve group, 3 (8.6%), presented with NNRTIs resistance mutations, along with polymorphic mutations to PIs in most (82.8%) of them. Among the failing therapy group, we detected a high frequency (89.4%) of resistance mutations to PIs, NRTI (84.8%), and NNRTI (59.1%). Virological suppression after introduction/modification of genotyping-guided ART was achieved only for patients (53.1%) with drug withdrawal over 95%. Main detected HIV-1 subtypes were B (67.3%), F (7.9), C (1.9%), and recombinant forms (22.9%). Despite the use of genotyping tests in guidance of a more effective antiretroviral regimen, poor adherence to ART seems to be the main determinant of low virological suppression rate for children and adolescents, in Salvador, Brazil.


Predictions for rapid methods and automation in food microbiology.
A discussion is presented on the present status of rapid methods and automation in microbiology. Predictions are also presented for development in the following areas: viable cell counts; real-time monitoring of hygiene; polymerase chain reaction, ribotyping, and genetic tests in food laboratories; automated enzyme-linked immunosorbent assay and immunotests; rapid dipstick technology; biosensors for Hazard Analysis Critical Control Point programs; instant detection of target pathogens by computer-generated matrix; effective separation and concentration for rapid identification of target cells; microbiological alert systems in food packages; and rapid alert kits for detecting pathogens at home.


Simple sequence repeat marker associated with a natural leaf defoliation trait in tetraploid cotton.
Cotton (Gossypium hirsutum L.) leaf defoliation has a significant ecological and economical impact on cotton production. Thus the utilization of a natural leaf defoliation trait, which exists in wild diploid cotton species, in the development of tetraploid cultivated cotton will not only be cost effective, but will also facilitate production of very high-grade fiber. The primary goal of our research was to tag loci associated with natural leaf defoliation using microsatellite markers in Upland cotton. The F2 populations developed from reciprocal crosses between the two parental cotton lines--AN-Boyovut-2 (2n = 52), a late leaf defoliating type, and Listopad Beliy (2n = 52), a naturally early leaf defoliating type--demonstrated that the naturally early leaf defoliation trait has heritability values of 0.74 and 0.84 in the reciprocal F2 population. The observed phenotypic segregation difference in reciprocal crosses suggested a minor cytoplasmic effect in the phenotypic expression of the naturally early leaf defoliation trait. Results from the Kruskal-Wallis (KW) nonparametric test revealed that JESPR-13 (KW = 6.17), JESPR-153 (KW = 9.97), and JESPR-178 (KW = 13.45) Simple sequence repeat (SSR) markers are significantly associated with natural leaf defoliation in the mapping population having stable estimates at empirically obtained critical thresholds (P < .05-.0001). JESPR-178 revealed the highest estimates (P < .0001) for association with the natural leaf defoliation trait, exceeding maximum empirical threshold values. JESPR-178 was assigned to the short arm of chromosome 18, suggesting indirectly that genes associated with natural leaf defoliation might be located on this chromosome. This microsatellite marker may have the potential for use to introgress the naturally early leaf defoliation quantitative trait loci (QTL) from the donor line Listopad Beliy to commercial varieties of cotton through marker-assisted selection programs.


Body Composition, Fitness Status, and Health Behaviors Upon Entering College: An Examination of Female College Students From Diverse Populations.
Although poor health-related behaviors that impact development of chronic diseases begin much earlier than when actual disease is evident, few studies have examined health behaviors in college students, who may be at an important transitional period where early intervention could prevent development of chronic diseases. The purpose of this study was to examine health-related factors in female college students (N = 61) by race/ethnicity and weight status. We found significant differences in health profiles between non-Hispanic White (White) and African American students, including greater physical fitness and healthier diets among White students. Overweight/obese students had worse health profiles than healthy BMI students. Furthermore, weight status was significantly associated with cardiovascular fitness. This supports a focus on PA promotion for interventions in the period of emerging adulthood, alongside the other healthy behaviors, to elicit improvements in weight status and potential reduction of chronic disease risks.


ICOSLG-associated immunological landscape and diagnostic value in oral squamous cell carcinoma: a prospective cohort study.
Background: We previously reported that stroma cells regulate constitutive and inductive PD-L1 (B7-H1) expression and immune escape of oral squamous cell carcinoma. ICOSLG (B7-H2), belongs to the B7 protein family, also participates in regulating T cells activation for tissue homeostasis via binding to ICOS and inducing ICOS+ T cell differentiation as well as stimulate B-cell activation, while it appears to be abnormally expressed during carcinogenesis. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for the maximum response rate of ICOSLG-based immunotherapy in a specific population. Methods: This retrospective study included OSCC tissue samples (n = 105) to analyze the spatial distribution of ICOSLG. Preoperative peripheral blood samples (n = 104) and independent tissue samples (n = 10) of OSCC were collected to analyze the changes of immunocytes (T cells, B cells, NK cells and macrophages) according to ICOSLG level in different cellular contents. Results: ICOSLG is ubiquitous in tumor cells (TCs), cancer-associated fibroblasts (CAFs) and tumor infiltrating lymphocytes (TILs). Patients with high ICOSLGTCs or TILs showed high TNM stage and lymph node metastasis, which predicted a decreased overall or metastasis-free survival. This sub-cohort was featured with diminished CD4+ T cells and increased Foxp3+ cells in invasive Frontier in situ, and increased absolute numbers of CD3+CD4+ and CD8+ T cells in peripheral blood. ICOSLG also positively correlated with other immune checkpoint molecules (PD-L1, CSF1R, CTLA4, IDO1, IL10, PD1). Conclusion: Tumor cell-derived ICOSLG could be an efficient marker of OSCC patient stratification for precision immunotherapy.


Use of oxfendazole to control porcine cysticercosis in a high-endemic area of Mozambique.
A randomized controlled field trial to evaluate the effectiveness of a single oral dose of 30 mg/kg of oxfendazole (OFZ) treatment for control of porcine cysticercosis was conducted in 4 rural villages of Angónia district, north-western Mozambique. Two hundred and sixteen piglets aged 4 months were selected and assigned randomly to OFZ treatment or control groups. Fifty-four piglets were treated at 4 months of age (T1), while another 54 piglets were treated at 9 months of age (T2) and these were matched with 108 control pigs from the same litters and raised under the same conditions. Baseline data were collected on the prevalence of porcine cysticercosis using antigen ELISA (Ag-ELISA), as well as knowledge and practices related to Taenia solium transmission based on questionnaire interviews and observations. All animals were followed and re-tested for porcine cysticercosis by Ag-ELISA at 9 and 12 months of age when the study was terminated. Overall prevalence at baseline was 5.1% with no significant difference between groups. At the end of the study, 66.7% of the controls were found positive, whereas 21.4% of the T1 and 9.1% of the T2 pigs were positive, respectively. Incidence rates of porcine cysticercosis were lower in treated pigs as compared to controls. Necropsy of 30 randomly selected animals revealed that viable cysts were present in none (0/8) of T2 pigs, 12.5% (1/8) of T1 pigs and 42.8% (6/14) of control pigs. There was a significant reduction in the risk of T. solium cysticercosis if pigs were treated with OFZ either at 4 months (OR = 0.14; 95% CI: 0.05-0.36) or at 9 months of age (OR = 0.05; 95% CI: 0.02-0.16). Strategic treatment of pigs in endemic areas should be further explored as a means to control T. solium cysticercosis/taeniosis.


Bromopyruvate as an active-site-directed inhibitor of the pyruvate dehydrogenase multienzyme complex from Escherichia coli.
Bromopyruvate behaves as an active-site-directed inhibitor of the pyruvate decarboxylase (E1) component of the pyruvate dehydrogenase complex of Escherichia coli. It requires the cofactor thiamin pyrophosphate (TPP) and acts initially as an inhibitor competitive with pyruvate (Ki ca. 90 microM) but then proceeds to react irreversibly with the enzyme, probably with the thiol group of a cysteine residue. E1 catalyzes the decomposition of bromopyruvate, the enzyme becoming inactivated once every 40-60 turnovers. Bromopyruvate also inactivates the intact pyruvate dehydrogenase complex in a TPP-dependent process, but the inhibition is more rapid and is mechanistically different. Under these conditions, bromopyruvate is decarboxylated, and the lipoic acid residues in the lipoate acetyltransferase (E2) component become reductively bromoacetylated. Further bromopyruvate then reacts with the new thiol groups thus generated in the lipoic acid residues, inactivating the complex. If reaction with the lipoic acid residues is prevented by prior treatment of the complex with N-ethylmaleimide in the presence of pyruvate, the mode of inhibition reverts to irreversible reaction with the E1 component. In both types of inhibition of E1, reaction of 1 mol of bromopyruvate/mol of E1 chain is required for complete inactivation, and all the evidence is consistent with reaction taking place at or near the pyruvate binding site.


Update on the 'index technique' in worn dentition: a no-prep restorative approach with a digital workflow.
Following the guidelines of the 'index technique' that were published in this journal in 2015, this article presents the 'digital index technique,' an updated no-prep restorative approach to the management of worn dentition. Patients with minimal, moderate, and severe hard tissue wear can be treated based on the application of minimally invasive or noninvasive adhesive composite restorations on posterior and anterior worn dentition. The technique allows for a purely additive treatment without sacrificing healthy hard tooth tissue. It follows the principles of biodentistry (maximum conservation of healthy tissue), and the reinforcing of residual dental structure. Depending on the severity of the enamel and dentin wear, the number of caries, and the size of the existing restorations, different treatment options can be applied to each tooth: direct and indirect partial restorations or full crowns. It is essential to diagnose and treat tooth surface loss in order to properly restore biomechanics, function, and esthetics by means of adhesive restorations. This article proposes that the update of the index technique through the digital workflow is a fast and conservative approach for the planning and management of a full-mouth adhesive restoration in all cases of light, moderate, and severe worn dentition. The technique is based on a 'copy-and-paste' guided approach, stamping composite resin directly onto the tooth surface by means of a transparent index created from a full-mouth digital restorative wax-up, following an initially planned increase in occlusal vertical dimension (OVD) through an esthetic and functional analysis.


Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration.
The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis.


[Mental illness among immigrants and refugees. Are needs and available care adequate?].
A considerable proportion of the Swedish population are of immigrant or refugee origin. This puts new demands on psychiatric care. In Stockholm county, immigrants of non-Scandinavian origin are characterised by lower psychiatric care utilisation rates than are the remainder of the county population. Population studies of multi-ethnic suburban areas in west Stockholm have shown the non-Scandinavian subgroup of the population to be characterised by somewhat lower utilisation of acute and short-term psychiatric care, as compared with native Swedes, but a clearly higher utilisation of primary psychiatric care facilities. Available evidence suggests the existence of several subgroups with high frequencies of mental ill-health in these areas. If sectorized psychiatry is to meet the demands of the population as a whole, economic prioritization is needed, as well as improved knowledge and methodology regarding cross-cultural psychiatry.


Recommendations for the surveillance of mental health problems in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.
Survivors of childhood, adolescent, and young adult (diagnosed when <25 years of age) cancer are at risk of mental health problems. The aim of this clinical practice guideline is to harmonise international recommendations for mental health surveillance in survivors of childhood, adolescent, and young adult cancer. This guideline was developed by a multidisciplinary panel of experts under the sponsorship of the International Guideline Harmonization Group. We evaluated concordance among existing survivorship clinical practice guidelines and conducted a systematic review following evidence-based methods. Of 7249 studies identified, 76 articles from 12 countries met the inclusion criteria. Recommendations were formulated on the basis of identified evidence in combination with clinical considerations. This international clinical practice guideline strongly recommends mental health surveillance for all survivors of childhood, adolescent, and young adult cancers at every follow-up visit and prompt referral to mental health specialists when problems are identified. Overall, the recommendations reflect the necessity of mental health surveillance as part of comprehensive survivor-focused health care.


Characterization of Antioxidant and Antimicrobial Activity and Phenolic Compound Profile of Extracts from Seeds of Different Vitis Species.
Seeds of Vitis vinifera L. with a high content of bioactive compounds are valuable by-products from grape processing. However, little is known about the bioactivity of seeds from other Vitis species. The aim of this study has been to compare the phenolic composition, antimicrobial activity, and antioxidant activity of extracts from seeds of four Vitis species (V. riparia Michx., V. californica Benth., V. amurensis Rupr., and V. vinifera L.). Antioxidant activities were assessed as ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging activity, and oxygen radical absorbance capacity (ORAC). The antimicrobial activity was determined using the microdilution method against some Gram-negative (Escherichia coli, Salmonella enterica ser. Typhimurium, and Enterobacter aerogenes) and Gram-positive (Enterococcus faecalis and Staphylococcus aureus) bacteria. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to evaluate the phenolic profile of extracts. Flavan-3-ols, procyanidins, phenolic acids, flavonols, anthocyanins, and stilbenoids were detected. (+)-Catechin and (-)-epicatechin turned out to be the most abundant in the phenolic profile of V. amurensis seed extract. Phenolic acids prevailed in the extract from V. vinifera seeds. The V. riparia and V. californica seed extracts had higher contents of most individual phenolics compared to the other Vitis species. They also showed a higher total phenolic content, DPPH• scavenging activity, ORAC, and overall antibacterial activity. Total phenolic content significantly correlated with antioxidant activity and antimicrobial activity against E. coli. The principal component analysis (PCA) showed discrimination between V. vinifera, V. amurensis, and clustered V. riparia and V. californica with respect to variables. To recapitulate, this research demonstrates that seeds of different Vitis species, especially V. riparia and V. californica, are sources of molecules with antioxidant and antimicrobial activities that can be used in different sectors, such as in the food, cosmetic, and pharmaceutical industries.


Does the pattern of occupational class inequalities in self-reported health depend on the choice of survey? A comparative analysis of four surveys and 35 European countries.
Despite increasing overall life expectancy, substantial differences in health between socioeconomic groups persist. Research on inequalities in health often draws on data from different, single surveys. An important question that arises is whether these surveys reflect health and inequalities in the same way. When occupational class is utilized, data are often not analysed for women. The aim of this study therefore is to investigate whether patterns of occupational class inequalities in self-reported health differ across sex and country, between four major European surveys. Data on self-reported health and occupational class are taken from the European Social Survey (ESS), the EU Statistics on Income and Living Conditions (EU-SILC), the European Working Conditions Survey (EWCS) and the International Social Survey Programme (ISSP). Data from 35 countries for men and women aged 25–65 years are analysed. Occupational class is measured according to manual and non-manual workers. Age-standardized prevalence rates, and prevalence ratios (PR) between non-manual and manual workers and likelihood ratio (LR) tests are estimated to determine occupational class inequalities in self-rated health in Europe. Results show that prevalence rates of less than good health differ noticeably between countries and surveys. Furthermore, occupational class inequalities in health differ between countries. In some countries inequalities are larger for women than for men. This is especially true in Eastern, Central and Baltic European countries. Besides that no regional patterns, consistent over all surveys, in inequalities could be detected. Inequalities differed significantly between surveys. The magnitude of inequalities in all countries depend on the survey used in the analysis. When undertaking a comparative analysis of inequalities in health, or other determinants, these differences have to be taken into account, as results might differ according to the data source used.


Synthetic control over magnetic moment and exchange bias in all-oxide materials encapsulated within a spherical protein cage.
This work focuses on the synthetic control of magnetic properties of mixed oxide magnetic nanoparticles of the general formula Fe(3-x)Co(x)O(4) (x < or = 0.33) in the protein cage ferritin. In this biomimetic approach, variations in the chemical synthesis result in the formation of single-phase Fe(3-x)Co(x)O(4) alloys or intimately mixed binary phase Fe/Co oxides, modifying the chemical structure and magnetic behavior of these particles, as characterized by static and dynamic magnetization measurements and X-ray absorption spectroscopy.


Intracranial angiomatoid fibrous histiocytoma with Hodgkin lymphoma.
Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumour of uncertain differentiation and low metastatic potential, which occurs predominantly in children and young adults. It occurs mostly within the extremities, trunk, head and neck. We report the case of a 32-year-old female that was operated in our hospital in 2016 and twice in 2017. The patient had headaches and neck pain initially in 2016. We discuss the radiographic and histologic features initially found and the findings that ultimately led to the diagnosis of AFH. The patient had a past history of Hodgkin lymphoma.


Primary structure of human urinary prokallikrein.
The complete amino acid sequence of human urinary prokallikrein has been determined by amino acid analysis and sequence determination of peptide fragments obtained from chemical and enzymological cleavages of kallikrein and by comparison of the N-terminal sequence of prokallikrein with that of kallikrein, the active form. Prokallikrein was a single chain polypeptide which comprised 238 amino acid residues of kallikrein and 7 amino acid residues of the propeptide. The sequence, Asn-X-Thr(Ser), which is a common glycosylation site was found at positions 78-80, 84-86, and 141-143. Two trypsin-susceptible sites were identified. One is the Arg(-1)-Ile(1) bond and the other is the Arg (87)-Gln(88) bond. The sequence of human urinary kallikrein was identical with that of human pancreatic and kidney kallikreins (Fukushima, D. et al. (1985) Biochemistry 24, 8037-8043; Baker, A.R. & Shine, J. (1985) DNA 4, 445-459), which were predicted from the nucleotide sequences of cDNAs. The primary structure of human urinary kallikrein is homologous to those of the other animal kallikreins and kallikrein-related proteins. Key amino acid residues, His(41), Asp(96), and Ser(190), required for catalytic activity and Asp (184) required for kallikrein-type specificity are completely conserved. The results show that human urinary prokallikrein and kallikrein are of tissue type and they are excreted in urine without any modification.


An integrated enhancement and reconstruction strategy for the quantitative extraction of actin stress fibers from fluorescence micrographs.
The stress fibers are prominent organization of actin filaments that perform important functions in cellular processes such as migration, polarization, and traction force generation, and whose collective organization reflects the physiological and mechanical activities of the cells. Easily visualized by fluorescence microscopy, the stress fibers are widely used as qualitative descriptors of cell phenotypes. However, due to the complexity of the stress fibers and the presence of other actin-containing cellular features, images of stress fibers are relatively challenging to quantitatively analyze using previously developed approaches, requiring significant user intervention. This poses a challenge for the automation of their detection, segmentation, and quantitative analysis. Here we describe an open-source software package, SFEX (Stress Fiber Extractor), which is geared for efficient enhancement, segmentation, and analysis of actin stress fibers in adherent tissue culture cells. Our method made use of a carefully chosen image filtering technique to enhance filamentous structures, effectively facilitating the detection and segmentation of stress fibers by binary thresholding. We subdivided the skeletons of stress fiber traces into piecewise-linear fragments, and used a set of geometric criteria to reconstruct the stress fiber networks by pairing appropriate fiber fragments. Our strategy enables the trajectory of a majority of stress fibers within the cells to be comprehensively extracted. We also present a method for quantifying the dimensions of the stress fibers using an image gradient-based approach. We determine the optimal parameter space using sensitivity analysis, and demonstrate the utility of our approach by analyzing actin stress fibers in cells cultured on various micropattern substrates. We present an open-source graphically-interfaced computational tool for the extraction and quantification of stress fibers in adherent cells with minimal user input. This facilitates the automated extraction of actin stress fibers from fluorescence images. We highlight their potential uses by analyzing images of cells with shapes constrained by fibronectin micropatterns. The method we reported here could serve as the first step in the detection and characterization of the spatial properties of actin stress fibers to enable further detailed morphological analysis.


Mild Cognitive Impairment and Driving Cessation: A 3-Year Longitudinal Study.
Driving cessation is associated with significant morbidity in older people. People with mild cognitive impairment (MCI) may be at particular risk of this. Very little research has examined driving in this population. Given this, we sought to identify predictors of driving cessation in people with MCI. One hundred and eighty-five people with MCI were recruited from 9 memory clinics around Australia. People with MCI and their carers reported their driving status and completed measures of cognition, function, neuropsychiatric symptoms, and medication use at regular intervals over a 3-year period. Of the 144 people still driving at baseline, 50 (27.0%) stopped driving during the study. Older age, greater cognitive and functional impairment, and greater decline in cognition and function at 6 months predicted subsequent driving cessation. Twenty-nine of the 50 people (58%) who stopped driving were diagnosed with dementia during the study; all except one of whom ceased driving after their dementia diagnosis. A significant proportion of people diagnosed with MCI stop driving over the following 3 years. This cannot be entirely attributed to developing dementia. Easily assessable characteristics - such as age, cognition, and function - and changes in these measures over 6 months predict driving cessation.


Role of cytokines and chemokines in alcohol-induced tumor promotion.
Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines and the oncogenic effect of alcohol. This review provides novel insight into the mechanisms of alcohol-induced tumor promotion.


Histologic classification as an indication of therapeutic response in malignant lymphoma of dogs.
In retrospective evaluation of treatment of canine malignant lymphoma, 12 of 13 dogs that had received doxorubicin alone or in combination with dacarbazine attained complete remission. Doxorubicin had been given alone, with combination chemotherapy being used only when complete remission could not be achieved and maintained with doxorubicin. The response to single or combined chemotherapy was correlated with histologic cell type of the malignant lymphoma. Histiocytic cell types did not respond to doxorubicin alone, but lymphoblastic types did respond. Combination chemotherapy was effective against histiocytic types. A mixed-cell type, which was initially responsive to doxorubicin alone, but not responsive after relapse, was observed to be histiocytic on rebiopsy.


Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis.
Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r=0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r=0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health.


Endobronchial ultrasound-guided transbronchial needle aspiration for thyroid cyst therapy: A case report.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is of limited usefulness for diagnosing thyroid disease, and few studies have reported its use in diagnosing and treating thyroid cysts. The present study investigated a unique case of diagnosis and treatment of a thyroid cyst by EBUS-TBNA. A 67-year-old male presented with back pain. Positron emission tomography/computed tomography scanning revealed low-density signals in the right lobe of the thyroid. Needle aspiration biopsies and drainage at this site was performed, and EBUS was used for guidance in diagnosing the thyroid cyst. A follow-up chest computed tomography scan indicated that the thyroid lesion had subsequently disappeared. The present study concludes that EBUS-TBNA provides an alternative approach for diagnosing and treating deep thyroid cysts located close to the airway. In all other cases, percutaneous needle aspiration or surgery should be the first choice.


Impact of Fasting Blood Glucose Levels on Blood Pressure Parameters among Older Adults with Prediabetes.
Prediabetes mellitus (pre-DM) is defined as blood glucose levels higher than normal but lower than the threshold for diabetes mellitus (DM) diagnosis. Four-limb blood pressure (BP) differences can help identify a significant risk for cardiovascular diseases (CVDs). The current study aimed to determine the importance of BP and the ankle-brachial index (ABI) between two patient groups and the association between fasting blood glucose (FBG) levels and four-limb BP, ABI, interarm BP difference (IAD), and interleg BP difference (ILD). Moreover, the effect of cardiovascular risk factors on the development of pre-DM among older adults was evaluated. The participants were divided into the normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Data on physical characteristics, lipid profiles, four-limb BP, ABI, IAD, ILD, and cardiovascular risk factors were assessed. The IFG group had a significantly higher systolic blood pressure (SBP) and pulse pressure than the NFG group (p < 0.05). SBP was significantly positively correlated with FBG levels (p < 0.05). The IFG group had a lower ABI than the NFG group (p < 0.05). However, there was no significant difference in terms of IAD and ILD between the two groups. Furthermore, hypertension (HT), metabolic syndrome (MetS), and dyslipidemia were significantly correlated with a high prevalence of prediabetes (p < 0.05). Individuals with prediabetes had a higher BP than those with normoglycemia. Prediabetes was correlated with HT, MetS, and dyslipidemia.


Structure and expression of mos sequences in spontaneous and Moloney murine sarcoma virus-induced yolk sac carcinomas in rats.
Facilitation of yolk-sac carcinoma (YSCa) development in fetectomized rats by the Moloney murine sarcoma virus/murine leukemia virus (Mo-MSV/MLV) complex was found to be closely associated with the presence of Mo-MSV sequences in the genomes of the YSCa cells. The virus-induced YSCas consisted of cells of mono- or oligoclonal origin which always contained in their genomes at least I randomly integrated Mo-MSV provirus. In YSCas which developed in the absence of virus, no rearrangement or amplification of c-mos could be detected. In addition, blot hybridization analysis of cellular RNA failed to detect mos-related RNA in cell lines derived from Mo-MSV-induced as well as from non-virally induced YSCas. The methylation level of c-mos DNA was low in all YSCa cell lines. In contrast, v-mos DNA in cell lines derived from Mo-MSV-induced YSCas was heavily methylated.


Detection of CALR Mutations Using High Resolution Melting Curve Analysis (HRM-A); Application on a Large Cohort of Greek ET and MF Patients.
Somatic mutations in the calreticulin gene (CALR) are detected in approximately 70% of patients with essential thrombocythemia (ET) and primary or secondary myelofibrosis (MF), lacking the JAK2 and MPL mutations. To determine the prevalence of CALR frameshift mutations in a population of MPN patients of Greek origin, we developed a rapid low-budget PCR-based assay and screened samples from 5 tertiary Haematology units. This is a first of its kind report of the Greek patient population that also disclosed novel CALR mutants. MPN patient samples were collected from different clinical units and screened for JAK2 and MPL mutations after informed consent was obtained. Negative samples were analyzed for the presence of CALR mutations. To this end, we developed a modified post Real Time PCR High-Resolution Melting Curve analysis (HRM-A) protocol. Samples were subsequently confirmed by Sanger sequencing. Using this protocol we screened 173 MPN, JAK2 and MPL mutation negative, patients of Greek origin, of whom 117 (67.63%) displayed a CALR exon nine mutation. More specifically, mutations were detected in 90 out of 130 (69.23%) essential thrombocythaemia cases (ET), in 18 out of 33 (54.55%) primary myelofibrosis patients (pMF) and in 9 out of 10 (90%) cases of myelofibrosis secondary to ET (post-ET sMF). False positive results were not detected. The limit of detection (LoD) of our protocol was 2%. Furthermore, our study revealed six rare novel mutations which are to be added in the COSMIC database. Overall, our method could rapidly and cost-effectively detect the mutation status in a representative cohort of Greek patients; the mutation make-up in our group was not different from what has been published for other national groups.


Beta thalassaemia mutations in Sardinians: implications for prenatal diagnosis.
In this study we have characterised by oligonucleotide hybridisation and direct restriction endonuclease analysis the beta thalassaemia mutation in 494 Sardinian beta thalassaemia heterozygotes. The most prevalent mutation, accounting for 95.4% of the cases, was the nonsense mutation at codon 39. The remainder, in decreasing order of frequency, were a frameshift at codon 6 (2.2%), beta + IVS-1, nt 110 (0.4%), and beta + IVS-2, nt 745 (0.4%). This information allows prenatal diagnosis by DNA analysis to be made in the great majority of Sardinian couples at risk for beta thalassaemia.


Combined iron chelator and T-type calcium channel blocker exerts greater efficacy on cardioprotection than monotherapy in iron-overload thalassemic mice.
Although both iron chelators and T-type calcium channel (TTCC) blockers have been shown to exert cardioprotection by decreasing cardiac iron deposition and reducing left ventricular (LV) dysfunction via different channels in iron-overloaded rodent models, the cardioprotective effects of combined iron chelator and TTCC blocker treatment in thalassemic mice has not been investigated. We hypothesized that a combined iron chelator and TTCC blocker exerts better cardioprotection than monotherapy by decreasing cardiac iron accumulation, apoptosis and oxidative stress. An iron-overload condition was induced in heterozygous βKO thalassemic (HT) mice and wild-type (WT) mice by high iron diet consumption (FE) for 3 months. Then, the iron chelator deferiprone (DFP), the TTCC blocker efonidipine (Efo), and combined DFP plus Efo were fed via oral gavage for 1 month whilst the high iron diet was continued. LV function, heart rate variability (HRV), apoptosis and cardiac iron accumulation were determined. Chronic iron-overload in mice led to increased cardiac iron deposition, oxidative stress, apoptosis, and impaired LV function and HRV. Although DFP and Efo showed similar cardioprotective efficacy, the combined DFP plus Efo therapy exerted greater efficacy in reducing cardiac iron deposition and cellular apoptosis than either of the monotherapies in iron-overload thalassemic mice.


Preoperative intravenous ibuprofen does not influence postoperative narcotic use in patients undergoing elective hernia repair: a randomized, double-blind, placebo controlled prospective trial.
Inguinal and umbilical hernia repairs are among the most common surgical procedures performed in the US. Optimal perioperative pain control regimens remain challenging and opioid analgesics are commonly used. Preoperative nonsteroidal anti-inflammatory drug (NSAID) administration has been shown to reduce postoperative narcotic requirements. This study sought to evaluate the efficacy of perioperative intravenous (IV) ibuprofen on postoperative pain level and narcotic use in patients undergoing open or laparoscopic inguinal and/or umbilical hernia repair. A single center, randomized, double-blind placebo-controlled trial involving patients ≥18 years undergoing inguinal and/or umbilical hernia repair was performed. Patients were randomized to receive 800 mg of IV ibuprofen or placebo preoperatively. Outcomes assessed included postoperative pain medication required and visual analog scale (VAS) pain scores. Forty-eight adult male patients underwent inguinal and/or umbilical hernia repair. Patients receiving IV ibuprofen used more oxycodone/acetaminophen (32% vs 13%) and IV hydromorphone (12% vs 8.7%), and fewer combinations of pain medications (44% vs 65.2%) in the first two postoperative hours compared to placebo (p=0.556). The IV ibuprofen group had more patients pain free (28% vs 8.7%, p=0.087) and lower VAS scores (3.08±2.14 vs 3.95±1.54, p=0.134) at 2 hours postoperatively, compared to the placebo group, however, this was not statistically significant. Similar pain levels at 1, 3, and 7 days, postoperative and similar use of rescue medications in both groups were observed. Preoperative administration of IV ibuprofen did not significantly reduce postoperative pain among patients undergoing elective hernia repair. Considerable variability in postoperative narcotic analgesic requirement was noted, and larger scale studies are needed to better understand the narcotic analgesic requirements associated with IV ibuprofen in inguinal/umbilical hernia repair patients.