Semisynthetic Abietic and Dehydroabietic Acid Derivatives and Triptoquinone Epimers Interfere with LPS-Triggered Activation of Dendritic Cells.
Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1β, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents.


Dual colorimetric and fluorogenic probes for visualizing tyrosine phosphatase activity.
Two resorufin-based substrates for protein tyrosine phosphatase (PTP) activity have been synthesized. These substrates provide sensitive fluorogenic readouts of PTP activity in vitro and in living cells at both acidic and neutral pH. In addition, the presence of the pathogenic bacteria Staphylococcus aureus was detected visually using a colorimetric readout.


[Group therapy through graphic art.].
In this article we describe and comment upon two graphic art therapy groups. Is it possible to accomplish work of a psycho-therapeutic nature in such groups? We attempt to respond to this question using examples taken from the experience of these different groups. First, we explain how the groups operate, our method of intervention, the general evolution, and finally, we present, in an in-depth fashion, the progress of one of the participants.


[The value of antibody coated bacteria in the evaluation of the level of urinary tract infections].
In 51 female and 43 male patients urinary tract infections (UTI) were detected by urinary cultures. The levels of UTI were detected by clinical and by physical studies, and by laboratory and X ray findings. In 42 of the patients, lower level UTI and in 52 patients upper level UTI were found. In 57.4% of the cases E. coli and in the remainder, proteus, pseudomonas, klebsiella, staphylococci and streptococci were found in decreasing rates as being the etiological agents of UTI. In 20 male and 32 female patients, upper level UTI were found. In the urine sediments of 85% males and 84.3% females with upper level UTI and in 13% males and 11% females with lower level UTI, antibody coated bacteria (ACB) were found to be positive. The difference of ABD in upper and lower level UTI was found to be significant and the detection of ACB by direct fluorescens method in urine sediments was shown to be valuable in the diagnosis of UTI.


Visual Servoed Three-Dimensional Cell Rotation System.
Three-dimensional (3-D) positioning and orientation of embryos/oocytes is necessary to facilitate micromanipulation tasks such as cell injection and cellular structural biopsy commonly performed under a microscope. Conventional cell orientation is performed manually by using a vacuum equipped micropipette to aspirate and release the cell, which is a trial-and-error approach. The conventional method relies heavily on the skill of the operator; it also suffers from low precision, low success rate and low controllability. These drawbacks illustrate the need for a systematic 3-D cell rotational system to automate the cell orientation process. In this paper, we present a noninvasive single cell rotation system that can automatically orientate a zebrafish embryo to a desired position when both the cytoplasm and the yolk are in the focal plane. A three-point-contact model for cell rotation that involves a custom-designed rotational stage is introduced to provide precise rotational position control. A vision recognition algorithm is also proposed to enable the visual servoing function of the system. Experimental results show that the proposed system can achieve high success rates of 92.5% (x-axis rotation with 40 trails) and 97.5% (about the z-axis with 80 trails). The system can also successfully complete 3-D cell orientation at an average speed of 31 s/cell with a high in-plane rotation accuracy of 0.3 (°) . As a high precise, high controllable and deterministic cell manipulating system, it provides a starting point for automated cell manipulation for intracytoplasmic sperm injection and embryo biopsy for preimplantation genetic diagnosis.


The modification of Sp3 isoforms by SUMOylation has differential effects on the SRC1A promoter.
Previously, we had described a housekeeping like promoter that regulates expression of the SRC gene in many cell types. This promoter was found to be regulated by Sp1 and hnRNP-K. However, at that time we could find little evidence supporting a significant role for Sp3 in SRC activation. Interestingly, despite its first description some 12 years ago, a full length Sp3 clone has only recently been described. Previous mechanistic studies, including our own, employed a version of Sp3 that was significantly N-terminally truncated. In addition, several shorter Sp3 isoforms exist that result from internally initiated translation sites. To complicate matters further, all Sp3 isoforms can be modified by SUMO-1. Due to this newly emerging information few reports exist that systematically explore these various Sp3 isoforms (SUMOylated or not) and how they affect activity of specific mammalian promoters. We therefore undertook such a study to re-evaluate regulation of SRC by these various Sp3 isoforms. Using human and insect cells we found that the newly isolated full length version of Sp3 was only a weak to moderate activator of SRC. However, to our surprise, the more commonly used N-terminally truncated version of Sp3 was up to five times more active. We also found that mutations preventing SUMOylation of the shorter Sp3 isoforms were sufficient to convert them into potent transactivators of SRC. In contrast to other studies, however, we found that SUMOylation of full length Sp3 had little effect on its transcriptional properties. These results provide new insights into the complexity of Sp3 mediated transcription which appears to be highly dependent on the isoform bound, SUMOylation status and the promoter context.


Lessons from the story of early child development: domain decisions and framing youth development.
This article maintains that effective communications strategy derives from a complex understanding of frame coherence. In particular, this understanding calls for a closer examination of the ways in which the "pictures in people's heads" are activated by exposure to a key arena of frame contestation: the issue domain. Drawing from FrameWorks' research on child development, the authors show that by choosing to align child development with specific domains, advocates may serve to further entrench public thinking in ways that imperil expert policy recommendations. Parallel cautions are drawn for youth issues, with further research from the FrameWorks portfolio. While aligning child and adolescent development with health, workforce, or education may result in further news coverage to those policies, research suggests it may also depress support for those same public policies.


Deep neck abscess: an analysis of microbial etiology and the effectiveness of antibiotics.
The objective was to demonstrate the aerobic and anaerobic microbiology of deep neck space abscess and to analyze the coverage rate of different empiric antimicrobial agents. A retrospective review of hospitalized patients with deep neck abscess diagnosed at a tertiary-care, general hospital between April 2001 and October 2006. The study enrolled 100 patients. The bacterial cultures of 89 patients yielded positive results (89%). The predominant aerobes were viridans streptococci, Klebsiella pneumoniae, and Staphylococcus aureus. The predominant anaerobes included species of Prevotella, Peptostreptococcus, and Bacteroides. Five different combinations of empiric antibiotics, namely regimen 1: penicillin G and clindamycin and gentamicin, regimen 2: ceftriaxone and clindamycin, regimen 3: ceftriaxone and metronidazole, regimen 4: cefuroxime and clindamycin, and regimen 5: penicillin and metronidazole, were compared using the antimicrobial susceptibility of 89 cases. The coverage rates of regimens 1, 2, 3, 4, and 5 were 67.4%, 76.4%, 70.8%, 61.8%, and 16.9%, respectively. The coverage of regimen 5 was considerably worse than that of the other four regimens (p < 0.001). Regimen 2 was significantly better than regimen 4 (p < 0.001). Regimen 2 had better coverage than regimens 1 (p = 0.096) and 3 (p = 0.302), but the difference was not statistically significant. This study demonstrates the bacteriology of deep neck abscess and analyzes the coverage rate of different empiric antimicrobial agents. Regimens 1, 2, and 3 could be good candidates for empiric antibiotics. Pathogen-directed antimicrobial therapy should be adjusted after the culture results are obtained.


Endocrine and bone metabolic complications in chronic liver disease and after liver transplantation in children.
With improved survival of orthotopic liver transplantation (OLT) in children, prevention and treatment of pre- and posttransplant complications have become a major focus of care. End-stage liver failure can cause endocrine complications such as growth failure and hepatic osteodystrophy, and, like other chronic illnesses, also pubertal delay, relative adrenal insufficiency, and the sick euthyroid syndrome. Drug-induced diabetes mellitus post-OLT affects approximately 10% of children. Growth failure is found in 60% of children assessed for OLT. Despite optimisation of nutrition, rarely can further stunting of growth before OLT be prevented. Catch-up growth is usually observed after steroid weaning from 18 months post-OLT. Whether growth hormone treatment would benefit the 20% of children who fail to catch up in height requires testing in randomised controlled trials. Hepatic osteodystrophy in children comprises vitamin D deficiency rickets, low bone mass, and fractures caused by malnutrition and malabsorption. Vitamin D deficiency requires aggressive treatment with ergocalciferol (D2) or cholecalciferol (D3). The active vitamin D metabolites alphacalcidol or calcitriol increase gut calcium absorption but do not replace vitamin D stores. Prevalence of fractures is increased both before OLT (10%-28% of children) and after OLT (12%-38%). Most fractures are vertebral, are associated with low spine bone mineral density, and frequently occur asymptomatically, but they may also cause chronic pain. Fracture prediction in these children is limited. OLT in children is also associated with a greater risk of developing avascular bone necrosis (4%) and scoliosis (13%-38%). This article reviews the literature on endocrine and skeletal complications of liver disease and presents preventive screening recommendations and therapeutic strategies.


The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae.
High levels of copper are toxic and therefore bacteria must limit free intracellular levels to prevent cellular damage. In this study, we show that a number of pneumococcal genes are differentially regulated by copper, including an operon encoding a CopY regulator, a protein of unknown function (CupA) and a P1-type ATPase, CopA, which is conserved in all sequenced Streptococcus pneumoniae strains. Transcriptional analysis demonstrated that the cop operon is induced by copper in vitro, repressed by the addition of zinc and is autoregulated by the copper-responsive CopY repressor protein. We also demonstrate that the CopA ATPase is a major pneumococcal copper resistance mechanism and provide the first evidence that the CupA protein plays a role in copper resistance. Our results also show that copper homeostasis is important for pneumococcal virulence as the expression of the cop operon is induced in the lungs and nasopharynx of intranasally infected mice, and a copA(-) mutant strain, which had decreased growth in high levels of copper in vitro, showed reduced virulence in a mouse model of pneumococcal pneumonia. Furthermore, using the copA(-) mutant we observed for the first time in any bacteria that copper homeostasis also appears to be required for survival in the nasopharynx.


An Overview of Metabolic Activity, Beneficial and Pathogenic Aspects of Burkholderia Spp.
Burkholderia is an important bacterial species which has different beneficial effects, such as promoting the plant growth, including rhizosphere competence for the secretion of allelochemicals, production of antibiotics, and siderophores. In addition, most of Burkholderia species have demonstrated promising biocontrol action against different phytopathogens for diverse crops. In particular, Burkholderia demonstrates significant biotechnological potential as a source of novel antibiotics and bioactive secondary metabolites. The current review is concerned with Burkholderia spp. covering the following aspects: discovering, classification, distribution, plant growth promoting effect, and antimicrobial activity of different species of Burkholderia, shedding light on the most important secondary metabolites, their pathogenic effects, and biochemical characterization of some important species of Burkholderia, such as B. cepacia, B. andropogonis, B. plantarii, B. rhizoxinica, B. glumae, B. caryophylli and B. gladioli.


Effects of macroalgae loss in an Antarctic marine food web: applying extinction thresholds to food web studies.
Antarctica is seriously affected by climate change, particularly at the Western Antarctic Peninsula (WAP) where a rapid regional warming is observed. Potter Cove is a WAP fjord at Shetland Islands that constitutes a biodiversity hotspot where over the last years, Potter Cove annual air temperatures averages increased by 0.66 °C, coastal glaciers declined, and suspended particulate matter increased due to ice melting. Macroalgae are the main energy source for all consumers and detritivores of Potter Cove. Some effects of climate change favor pioneer macroalgae species that exploit new ice-free areas and can also decline rates of photosynthesis and intensify competition between species due to the increase of suspended particulate matter. In this study, we evaluated possible consequences of climate change at Potter Cove food web by simulating the extinction of macroalgae and detritus using a topological approach with thresholds of extinction. Thresholds represent the minimum number of incoming links necessary for species' survival. When we simulated the extinctions of macroalgae species at random, a threshold of extinction beyond 50% was necessary to obtain a significant number of secondary extinctions, while with a 75% threshold a real collapse of the food web occurred. Our results indicate that Potter Cove food web is relative robust to macroalgae extinction. This is dramatically different from what has been found in other food webs, where the reduction of 10% in prey intake caused a disproportionate increase of secondary extinctions. Robustness of the Potter Cove food web was mediated by omnivory and redundancy, which had an important relevance in this food web. When we eliminated larger-biomass species more secondary extinctions occurred, a similar response was observed when more connected species were deleted, yet there was no correlation between species of larger-biomass and high-degree. This similarity could be explained because both criteria involved key species that produced an emerging effect on the food web. In this way, large-biomass and high-degree species could be acting as source for species with few trophic interactions or low redundancy. Based on this work, we expect the Potter Cove food web to be robust to changes in macroalgae species caused by climate change until a high threshold of stress is reached, and then negative effects are expected to spread through the entire food web leading to its collapse.


Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors.
Inhibitors of bacterial ureases are considered to be promising compounds in the treatment of infections caused by Helicobacter pylori in the gastric tract and/or by urealytic bacteria (e.g., Proteus species) in the urinary tract. A new, extended transition state scaffold, bis(aminomethyl)phosphinic acid, was successfully explored for the construction of effective enzyme inhibitors. A reliable methodology for the synthesis of phosphinate analogues in a three-component Mannich-type reaction was elaborated. The obtained molecules were assayed against ureases purified from Sporosarcina pasteurii and Proteus mirabilis, and aminomethyl(N-n-hexylaminomethyl)phosphinic acid was found to be the most potent inhibitor, with a K i = 108 nM against the S. pasteurii enzyme.


Role of Counterions in Controlling the Properties of Ultrasonically Generated Chitosan-Stabilized Oil-in-Water Emulsions.
An oil-in-water emulsion was ultrasonically prepared in aqueous chitosan solutions containing different counterions. Tetradecane was used as the oil phase in order to mimic nonpolar substances used in food processes. Various acids were used to dissolve chitosan, and we found that conjugate bases of the acids used, which act as counterions to neutralize the positive charges of ammonium ions present in the chitosan backbone, played a significant role in controlling the size, size distribution, and stability of chitosan-encapsulated tedradecane emulsion droplets (microspheres). The counterion effect is also found to be strongly dependent upon tetradecane (TD)/chitosan (CS) ratio and ultrasonic power. Key observations are: (i) for a given TD/CS ratio, the size and size distribution decrease when the acid is varied from nitric acid to benzenesulfonic acid at high TD/CS ratio, and the effect becomes less significant at low TD/CS ratio; (ii) for a given acid, the size and size distribution increase with an increase in TD/CS ratio; and (iii) at low TD/CS ratio the size and size distribution are significantly influenced by the viscosity of the system. A possible mechanism for the observed counterion effect is proposed. The role of counterions, solution viscosity, and ultrasonic power in controlling the physical and functional properties of ultrasonically generated chitosan-stabilized tetradecane microspheres is discussed in detail. The key new finding of this study is that it is possible to form stable emulsions without the addition of external emulsifiers and stabilizers, but only using chitosan with different acids to dissolve chitosan. This strategy could be used in the generation of stable food emulsions.


Soft and Stretchable Liquid Metal-Elastomer Composite for Wearable Electronics.
Soft devices, especially capacitive stress (or strain) sensors, are important for applications, including wearable medical monitoring, electronic skin, and soft robotics. The incorporation of liquid metal particles (LMPs) into highly deformable elastomers as inclusions ameliorates the mechanical compliance caused by a rigid filler. The high dielectric constant and liquid feature of LMPs are suitable for soft sensors with high sensitivity and a large real-time dynamic detection range. Here, a class of LM-elastomer composites are introduced with elastic and high dielectric properties, making them uniquely suitable for the application of soft stress sensors. The prepared stretchable soft stress sensor can detect the bending degree of the finger, monitor physiological signals in real time, and distinguish the vibration from the pronunciation of different letters. The nanoscale X-ray computational tomography (nano-CT) measurements indeed detect the changes of LMPs under stress, i.e., LMPs in the matrix distribute from uneven to relatively uniform, agglomerate, and even connect each other to have a conduction path in the composition with high LMP contents, which cause the changes in the physical properties of devices under operation. The cognition of LMP changes in composites under stress is instructive for promoting their further applications in the field of soft devices.


Expression of mutant ubiquitin (UBB+1) and p62 in myotilinopathies and desminopathies.
Protein aggregates in muscle cells are the morphological hallmark of myofibrillar myopathies, including myotilinopathies and desminopathies. The aim of the present study is to analyse the expression of mutant ubiquitin (UBB+1), an aberrant form of ubiquitin which accumulates in certain disorders characterized by intracellular aggregates of proteins, and p62, a multimeric signal protein which plays an active role in aggregate formation, in muscle biopsies from patients suffering from myotilinopathy and desminopathy in order to gain understanding of the mechanisms leading to protein aggregation in these disorders. Single immunohistochemistry, and single- and double-labelling immunofluorescence and confocal microscopy for UBB+1 and p62, has been performed in muscle biopsies from patients suffering from myotilinopathy and desminopathy. Strong UBB+1 immunoreactivity, colocalizing with myotilin aggregates, was found in muscle fibres in myotilinopathies. UBB+1 accumulation, colocalizing with desmin aggregates, also occurs in desminopathies. In addition, strong p62 immunoreactivity colocalizing with myotilin aggregates was observed in myotilinopathies. Similarly, p62 immunoreactivity colocalizing with desmin aggregates was found in desminopathies. The present findings suggest that accumulation of protein aggregates in myotilinopathies and in desminopathies may be related with UBB+1/abnormal protein complexes which are resistant to proteasome degradation. Furthermore, these observations suggest a relationship between the presence of p62 and the formation of inclusions in different subtypes of myofibrillar myopathies.


The interval between menarche and age of first sexual intercourse as a risk factor for subsequent HPV infection in adolescent and young adult women.
We sought to determine whether the interval between menarche and age of first sexual intercourse is associated with subsequent human papilloma virus (HPV) infection and if so, whether the association is independent of the age of first sexual intercourse. Female university students completed a survey and were screened for cervicovaginal HPV infection. HPV-positive subjects were matched to HPV-negative subjects (n = 504). Mean subject age was 20.4 +/- 2.1 years, age of first sexual intercourse 16.7 +/- 1.8 years, and interval 4.4 +/- 2.0 years. The interval was associated with HPV infection, but the association became nonsignificant in univariate stratified analyses and multivariate models estimating the association between the interval and HPV infection. A short interval is associated with HPV infection, but the association is not independent of age of first sexual intercourse. Age of first sexual intercourse should be considered an important and identifiable risk factor for subsequent HPV infection in research and clinical settings.


Complete heart block induced by general anesthesia in a patient with suspected conduction system defect: a case report.
We report a rare incident of complete heart block occurring after induction of general anesthesia in an apparently fit patient. An external temporary pacemarker was first applied, which was then replaced by isoproterenol infusion, but permanent pacing was required postoperatively. The role of anesthesia as a precipitating factor was discussed. It is suggested that surgical patients suspicious of conduction system defect should be under continuous hemodynamic monitoring with temporary pacing at hand during perioperative period.


Ultrasound characterization of mammary gland development in heifer calves fed at two different levels until weaning.
Ultrasound technologies allow for a non-invasive assessment of mammary gland (MG) development, the differentiation between the tissue types of the MG, and the evaluation of changes in its composition. This study aimed to work out a detailed description of the different stages of MG development that are visually discernible by ultrasonography for providing a template to classify the different structures. With this basis, the qualitative categorization of the developmental stage, as well as further quantitative assessments via pixel densities in the structures of interest, should be facilitated. Ultrasonic images were acquired from all four quarters of 37 German Holstein heifer calves fed either at a high feeding level of milk replacer (MR; 14% solids) at 10 L/day (1.4 kg MR/day; HI, n = 18) or at a restrictive low level of 5.7 L/day (0.8 kg MR/day; RES, n = 19) until linear weaning from week 13 to 14 of life. Ultrasound MG scans were performed first in week 3 of life, fortnightly from week 8-16, and in week 20 of life, in standing position, of each quarter, using a B-mode ultrasound device equipped with a linear probe (18 MHz). The developmental stages of the mammary gland parenchyma (PAR), visible in ultrasound images, obtained over 20 weeks of life, were categorized, described, and drawn by hand. On this basis, a template for classifying the visible categories of mammary PAR development and its surrounding tissue (SURR), and for measuring their pixel brightness was created thus providing an ultrasonographic atlas of the developing bovine MG, describing 11 categories. The ultrasound images were further classified by PAR structure, and pixel brightness was measured in PAR and SURR by using ImageJ Fiji. The difference in pixel brightness between PAR and SURR, the delta (Δ) pixel value was calculated. With increasing age, higher atlas categories of PAR developmental stages were shown. Pixel values, i.e. the brightness of PAR, its SURR, and Δ pixel value changed with age but were neither affected by the feeding group nor by a group × time interaction. With progressing PAR development, its pixel brightness increased from week 10 to 20 of life, i.e., the PAR became more hyperechoic since it spread and grew into its SURR. The atlas can serve as a template for the categorization and qualitative assessment of MG structures and for the quantitative assessment of PAR's development by measuring pixel brightness. With our study, we could show the structural development in PAR as well as in SURR in MG simultaneously in early life and confirm the spreading of PAR into its SURR by ultrasound scanning.


Pathway switching explains the sharp response characteristic of hypoxia response network.
Hypoxia induces the expression of genes that alter metabolism through the hypoxia-inducible factor (HIF). A theoretical model based on differential equations of the hypoxia response network has been previously proposed in which a sharp response to changes in oxygen concentration was observed but not quantitatively explained. That model consisted of reactions involving 23 molecular species among which the concentrations of HIF and oxygen were linked through a complex set of reactions. In this paper, we analyze this previous model using a combination of mathematical tools to draw out the key components of the network and explain quantitatively how they contribute to the sharp oxygen response. We find that the switch-like behavior is due to pathway-switching wherein HIF degrades rapidly under normoxia in one pathway, while the other pathway accumulates HIF to trigger downstream genes under hypoxia. The analytic technique is potentially useful in studying larger biomedical networks.


Allopreening in birds is associated with parental cooperation over offspring care and stable pair bonds across years.
Individuals of many species form bonds with their breeding partners, yet the mechanisms maintaining these bonds are poorly understood. In birds, allopreening is a conspicuous feature of interactions between breeding partners and has been hypothesized to play a role in strengthening and maintaining pair bonds within and across breeding attempts. Many avian species, however, do not allopreen and the relationship between allopreening and pair bonding across species remains unexplored. In a comparative analysis of allopreening and pair bond behavior, we found that allopreening between breeding partners was more common among species where parents cooperate to rear offspring. The occurrence of allopreening was also associated with an increased likelihood that partners would remain together over successive breeding seasons. However, there was no strong evidence for an association between allopreening and sexual fidelity within seasons or time spent together outside the breeding season. Allopreening between partners was also no more common in colonial or cooperatively breeding species than in solitary species. Analyses of evolutionary transitions indicated that allopreening evolved from an ancestral state of either high parental cooperation or high partner retention, and we discuss possible explanations for this. Overall, our results are consistent with an important role for allopreening in the maintenance of avian pair bonds.


Fine vascular anatomy of adult rabbit knee ligaments.
The microvascular anatomy of discrete knee ligaments in adult rabbits is described. Epiligamentous plexuses give rise to a limited number of vessels which penetrate deeply into ligament substance. Intraligamentous vessels are usually longitudinally orientated, widely separated linear anastomoses but occasionally complex glomus-like configurations are present. The significance of these findings is discussed in relation to other articular connective tissues and to the possible roles of the intraligamentous microvasculature.


Probing the effects of mild traumatic brain injury with transcranial magnetic stimulation of the primary motor cortex.
The present paper systematically reviews studies using transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) to assess cortical excitability, intra-cortical inhibition/facilitation and synaptic plasticity following mild traumatic brain injury (mTBI). Articles using TMS over M1 in patients with mTBI or sport-related concussion indexed in PubMed and published between 1998 and September 2014 were included in the present review. From the 17 articles that matched search criteria, results from various TMS paradigms were summarized and divided in three main areas of interest: motor cortical excitability/facilitation, motor cortical inhibition and cortical plasticity. Although studies suggest a trend of abnormal intra-cortical inhibition following mTBI, no clear and specific pattern emerges from the surveyed data. At this time and with the possible exception of intra-cortical inhibitory measures, TMS cannot reliably detect changes in M1 excitability in individuals with mTBI or a concussion at both the acute and chronic stages of injury. This may be explained by the small number of studies and large variety of stimulation parameters. Additional longitudinal and multimodal studies are needed to better understand the nature of the excitability changes that may occur within M1 following mTBI.


Interaction between Charge-Regulated Metal Nanoparticles in an Electrolyte Solution.
We present a theory which allows us to calculate the interaction potential between charge-regulated metal nanoparticles inside an acid-electrolyte solution. The approach is based on the recently introduced model of charge regulation which permits us to explicitly-within a specific microscopic model-relate the bulk association constant of a weak acid to the surface association constant for the same weak acid adsorption sites. When considering metal nanoparticles we explicitly account for the effect of the induced surface charge in the conducting core. To explore the accuracy of the approximations, we compare the ionic density profiles of an isolated charge-regulated metal nanoparticle with explicit Monte Carlo simulations of the same model. Once the accuracy of the theoretical approach is established, we proceed to calculate the interaction force between two charge-regulated metal nanoparticles by numerically solving the Poisson-Boltzmann equation with charge regulation boundary condition. The force is then calculated by integrating the electroosmotic stress tensor. We find that for metal nanoparticles the charge regulation boundary condition can be well approximated by the constant surface charge boundary condition, for which a very accurate Derjaguin-like approximation was recently introduced. On the other hand, a constant surface potential boundary condition often used in colloidal literature, shows a significant deviation from the charge regulation boundary condition for particles with large charge asymmetry.


Increased neuronal expression of alpha B-crystallin in human olivary hypertrophy.
We studied morphologic changes in olivary hypertrophy from dentato-olivary tract lesions by immunohistologic methods with antialpha B-crystallin and antiheat shock protein 27 (HSP 27). The majority of central chromatolysis-like enlarged neurons, which are frequently seen in the early stages of olivary hypertrophy on ipsilateral lesions, showed a marked expression of alpha B-crystallin; however, HSP 27 did not show increased expression in those neurons. In the later stages of olivary hypertrophy, increased expressions of alpha B-crystallin varied in the remaining neurons and the expression of HSP 27 increased in hypertrophied astrocytes, although the expression of alpha B-crystallin in hypertrophic astrocytes was not prominent. The accumulation of alpha B-crystallin and HSP 27 may represent responses to pathologic conditions.


The attitudes of obstetric caregivers towards labour pain relief methods and associated factors at public health centers of East Gojjam zone, Amhara Region, Ethiopia: Institutional based cross-sectional study.
labour pain relief is a key factor for maternal satisfaction during childbirth. However, in developing countries, labour pain management is not a well-established service mainly due to negative attitudes of health care providers resulting in unmeasured suffering from childbirth for mothers. Thus, this study was aimed to assess attitude of obstetric caregiver towards labour pain management and associated factors at public health centers of East Gojjam zone. institutional-based cross-sectional study was conducted from March 1-30, 2018. Three hundred and nine sampled obstetric caregivers have participated, with a 96.8%(299) response rate. Data were collected with structured pretested questionnaires. Data were entered into Epi data 4.2 versions and bivariate and multivariate logistic regression was carried out using SPSS 23 versions with 95 % CI to determine the association between dependent and independent variables. out of the study participants, 128 (42.8%) had a negative attitude towards managing labour pain. Knowledge (AOR =3.785, 95 % CI: 2.251,6.365), training (AOR=2.923, 95% CI: 1.266, 6.749) and Companion (AOR=1.834, 95% CI: 1.055, 3.189) had significantly associated with attitude of obstetric caregiver towards labour pain relief methods. the result of this study showed that there is still a negative attitude towards labour pain management among obstetric caregivers in the study setting. Providing knowledge-based in-service training for obstetric caregivers to change their attitude towards labour pain relief methods is advisable.


Plastic corticostriatal circuits for action learning: what's dopamine got to do with it?
Reentrant corticobasal ganglia circuits are important for voluntary action and for action selection. In vivo and ex vivo studies show that these circuits can exhibit a plethora of short- and long-lasting plastic changes. Convergent evidence at the molecular, cellular, and circuit levels indicates that corticostriatal circuits are involved in the acquisition and automatization of novel actions. There is strong evidence that activity in corticostriatal circuits changes during the learning of novel actions, but the plastic changes observed during the early stages of learning a novel action are different than those observed after extensive training. A variety of studies indicate that the neural mechanisms and the corticostriatal subcircuits involved in the initial acquisition of actions and skills differ from those involved in their automatization or in the formation of habits. Dopamine, a critical modulator of short- and long-term plasticity in corticostriatal circuits, is differentially involved in early and late stages of action learning. Changes in dopaminergic transmission have several concomitant effects in corticostriatal function, which may be important for action selection and action learning. These diverse effects may subserve different roles for dopamine in reinforcement and action learning.


Ontogenesis of opercular deformities in gilthead sea bream Sparus aurata: a histological description.
The aim of this study was to characterize histological changes during opercular osteogenesis in farmed gilthead sea bream Sparus aurata larvae from 7 to 69 days post hatching (dph) and compare normal osteogenesis with that of deformed opercles. Mild opercular deformities were first detected in 19 dph larvae by folding of the opercle's distal edge into the gill chamber. Here, the variation in the phenotype and the irregular bone structure at the curled part of the opercles is described and compared with the histology of normal opercles. Results indicated that deformed opercles still undergo bone growth with the addition of new matrix by osteoblasts at the opercular surface, especially at its edges. No significant difference was found in bone thickness between deformed and normal opercles. In addition to differences in bone architecture, differences in collagen fibre thickness between normal and deformed opercles were also found.


The colorectal cancer patients' journey: the Auckland region.
To identify the time taken from referral to first treatment of patients with colorectal cancer (CRC) in the Auckland region and benchmark these against available guidelines for timeliness. Retrospective study of clinical records of all patients diagnosed with CRC identified from the national registry and Auckland regional databases in the years 2001 and 2005. Data extracted included demographics, dates and types of interventions and the patient journey from referral to initiation of first treatment. Of the 1128 patients diagnosed and treated in these cohorts, 68% were referred through their general practitioner and 58% saw a surgeon at their first specialist appointment. Seventy-nine percent received initial treatment with curative intent. The median time from initial referral to first treatment was 35 days, with only 68% of patients being treated within 62 days of initial referral. The colorectal patient journey is complicated by multiple pathways of presentation and treatment and by patient choice. These factors need to be considered when assessing the acceptability of transit times based on summary data. That nearly one-third of patients did not complete the United Kingdom-based target of 62 days from referral to first treatment indicates there is a need for further improvement in service delivery for patients developing CRC in the Auckland region.


Susceptibility of Mycobacterium avium and Mycobacterium intracellulare to various antibacterial drugs.
Mycobacterium avium and M. intracellulare of human and natural sources, identified by the Gen-Probe Rapid Diagnostic System for M. avium Complex (MAC) were studied for susceptibility to eight different drugs. In the case of human isolates of MAC, the following was noted. M. avium showed nearly the same susceptibility to streptomycin, kanamycin, ethambutol, and clofazimine as was seen with M. intracellulare. M. avium was much more resistant to rifampicin and rifabutin than was M. intracellulare, and M. avium was more susceptible to quinolones such as ofloxacin and ciprofloxacin. Conversely, in the case of MAC from natural sources, there was no difference between the susceptibility of M. avium and M. intracellulare to these antibacterial agents.


NRF2 deficiency reduces life span of mice administered thoracic irradiation.
Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-β and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-β-mediated signaling, assessed by measuring expression of a surrogate TGF-β1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2(-/-) mice resulted in rapid expression of PAI-1 and FSP-1 compared to irradiated wild-type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2(-/-) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild-type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2(+/-) and Nfe2l2(-/-) mice exhibited a mean life span of 176 days compared to wild-type mice, which lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for the development of late tissue injury.


Plant lipid phosphate phosphatases: current advances and future outlooks.
Lipids are widely distributed in various tissues of an organism, mainly in plant storage organs (e.g., fruits, seeds, etc.). Lipids are vital biological substances that are involved in: signal transduction, membrane biogenesis, energy storage, and the formation of transmembrane fat-soluble substances. Some lipids and related lipid derivatives could be changed in their: content, location, or physiological activity by the external environment, such as biotic or abiotic stresses. Lipid phosphate phosphatases (LPPs) play important roles in regulating intermediary lipid metabolism and cellular signal response. LPPs can dephosphorylate lipid phosphates containing phosphate monolipid bonds such as: phosphatidic acid, lysophosphatidic acid (LPA), and diacylglycerol pyrophosphate, etc. These processes can change the contents of some important lipid signal mediation such as diacylglycerol and LPA, affecting lipid signal transmission. Here, we summarize the research progress of LPPs in plants, emphasizing the structural and biochemical characteristics of LPPs and their role in spatio-temporal regulation. In the future, more in-depth studies are required to boost our understanding of the key role of plant LPPs and lipid metabolism in: signal regulation, stress tolerance pathway, and plant growth and development.


Machine learning models to predict micronutrient profile in food after processing.
The information on nutritional profile of cooked foods is important to both food manufacturers and consumers, and a major challenge to obtaining precise information is the inherent variation in composition across biological samples of any given raw ingredient. The ideal solution would address precision and generability, but the current solutions are limited in their capabilities; analytical methods are too costly to scale, retention-factor based methods are scalable but approximate, and kinetic models are bespoke to a food and nutrient. We provide an alternate solution that predicts the micronutrient profile in cooked food from the raw food composition, and for multiple foods. The prediction model is trained on an existing food composition dataset and has a 31% lower error on average (across all foods, processes and nutrients) than predictions obtained using the baseline method of retention-factors. Our results argue that data scaling and transformation prior to training the models is important to mitigate any yield bias. This study demonstrates the potential of machine learning methods over current solutions, and additionally provides guidance for the future generation of food composition data, specifically for sampling approach, data quality checks, and data representation standards.


[Stoma prolapse and stoma retraction].
Prolapse and retraction of an intestinal stoma are postoperative complications which severely decrease the quality of life of patients and in some cases lead to an operative revision. Both entities should be treated with sophisticated care by specialized stoma therapists in the early phase in order to prevent secondary problems such as dermal ulceration. However, in case of additional problems, such as ileus, bleeding, incarceration or impossibility of adequate stoma care, an operative revision is indicated. It remains an individual decision whether a local or a transabdominal revision of the stoma is necessary.At present the level of information and the number of well designed studies dealing with prolapse or retraction of a stoma are unsatisfactory and there are merely studies which report on prolapse and retraction as an incidental finding rather than primarily focusing on these problems. In addition there is a lack of clear cut definitions for both entities which would allow a comparison of data obtained in different studies.There is clearly a demand for a structured scientific clarification as the occurrence of stomal retraction or prolapse may present psychological and medical problems for the patients and therefore needs to be treated, conservatively and/or operatively, by both stoma specialists and surgeons.


A graphene hybrid supramolecular hydrogel with high stretchability, self-healable and photothermally responsive properties for wound healing.
Wound healing is a ubiquitous healthcare problem in clinical wound management. In this paper, the fabrication of a graphene hybrid supramolecular hydrogel (GS hydrogel) for wound dressing applications is demonstrated. The hydrogel is composed of two components, including N-acryloyl glycinamide (NAGA) as the scaffold and graphene as the photothermally responsive active site for photothermal therapy. Based on the multiple hydrogen bonds between the dual amide motifs in the side chain of N-acryloyl glycinamide, the hydrogel exhibits high tensile strength (≈1.7 MPa), good stretchability (≈400%) and self-recoverability. In addition, the GS hydrogel shows excellent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), benefiting from the addition of graphene that possesses great photothermal transition activity (≈85%). Significantly, in vivo animal experiments also demonstrated that the GS hydrogel effectively accelerates the wound healing processes by eradicating microbes, promoting collagen deposition and angiogenesis. In summary, this GS hydrogel demonstrates excellent mechanical performance, photothermal antimicrobial activity, and promotes skin tissue regeneration, and so has great application potential as a promising wound dressing material in clinical use.


New insight into clinical development of nucleic acid aptamers.
Nucleic acid-based aptamers have been shown as high-affinity ligands and potential antagonists of disease-associated proteins. Aptamers, isolated from combinatorial libraries by an iterative in vitro selection process, discriminate between closely related targets and are characterized by high specificity and low toxicity thus representing a valid alternative to antibodies to target specific proteins of biomedical interest. Moreover, they are non-immunogenic and can be easily stabilized by chemical modifications thus expanding their therapeutic potential. Here, we will focus on the structural and functional features of aptamers that have entered the clinical development pipeline together with those aptamers holding great potential as therapeutics in preclinical studies. The future perspectives of aptamers as therapeutics will be discussed as well.


Violence against women--what are ICM and its member associations doing about it?
Midwives are in a key position to address issues surrounding violence against women (VAW). The International Confederation of Midwives is committed to keeping VAW on the world's health agenda and make sure all the issues receive the necessary attention.


Exploring the Interactions between Housing and Neighbourhood Environments for Enhanced Child Wellbeing: The Lived Experience of Parents Living in Areas of High Child Poverty in England, UK.
Children's health can be affected by the interrelated characteristics of the physical and social environment where they live, including housing quality, neighbourhood characteristics and the local community. Following a systems-based approach, this exploratory project sought to understand how the needs and aspirations associated with the home environment can work in synergy with, or be exacerbated by, other aspects of the local area. The study recruited parents of children aged 2-12 years old from two local authorities in England with high levels of child poverty: Tower Hamlets in East London, and Bradford District in West Yorkshire. Thematic analysis of participant interviews highlighted ten themes and opportunities for improvements. The evidence presented in this research emphasises how environmental quality issues within and outside the home, compounded further by delays in repairs and reduction in service standards, as well as affordability issues, are likely to deeply affect the wellbeing of an entire generation of disadvantaged children whose parents can feel disempowered, neglected and often isolated when attempting to tackle various dimensions of inequalities. Interventions which can improve the quality of housing, and access to space and services, are urgently needed, including initiatives to support and empower families and local communities, especially those prioritising opportunities for action.


Adjuvant radiotherapy in Stage I endometrial cancer. Where do we stand?
This paper reviews the anatomical spread and failure patterns of surgical Stage I endometrial cancer. The controversial aspects of the optimal adjuvant treatment are presented. An attempt is made to identify the most effective management approach based on the pertinent literature data.


P-Akt/miR‑200 signaling regulates epithelial-mesenchymal transition, migration and invasion in circulating gastric tumor cells.
Both circulating tumor cells (CTCs) and epithelial-mesenchymal transition (EMT) play an important role in invasion, migration and chemoresistant in tumor development. This study aimed to detect whether EMT occurred in human gastric CTCs and to explore the mechanism of EMT in human gastric CTCs. We analysed epithelial markers (pan-CK, E-cadherin), mesenchymal markers (N-cadherin, vimentin) EMT related miR‑200s, and Akt in gastric CTCs. The impact of miR‑200s on EMT, migration and invasion in CTCs was tested. We found that epithelial markers pan-CK, E-cadherin were decreased, and mesenchymal markers N-cadherin, vimentin were overexpressed in gastric CTCs. Expression of EMT related transcriptors, snail1, zeb1, twist1, were reversely correlated with miR‑200s, and were positively correlated with phospho-Akt. Upregulated of miR‑200s downregulated twist1 and zeb1 mRNA expression, and resulted in the supression of EMT, and impaired migration and invasion in gastric CTCs. Inhibition of p-Akt led to upregulation of miR‑200s. In conclusion, gastric CTCs exhibited remarkable EMT process, and p-Akt/miR‑200s signaling regulates EMT, migration and invasion in gastric CTCs.


Global health database.
The Global Health database is available from Ovid Technologies, Inc., and also from CABI Publishing, EBSCO, and DataStar/ DIALOG. This database is really the combination of two others--the Public Health and Tropical Medicine database, formerly produced by the Bureau of Hygiene and Tropical Diseases, as well as human health and diseases information that is extracted from the CAB Abstracts database. This column will provide readers with an overview of the Global Health database, as well as present some searching hints. The Ovid interface will be used.


Nonlinear multiscale wavelet diffusion for speckle suppression and edge enhancement in ultrasound images.
This paper introduces a novel nonlinear multiscale wavelet diffusion method for ultrasound speckle suppression and edge enhancement. This method is designed to utilize the favorable denoising properties of two frequently used techniques: the sparsity and multiresolution properties of the wavelet, and the iterative edge enhancement feature of nonlinear diffusion. With fully exploited knowledge of speckle image models, the edges of images are detected using normalized wavelet modulus. Relying on this feature, both the envelope-detected speckle image and the log-compressed ultrasonic image can be directly processed by the algorithm without need for additional preprocessing. Speckle is suppressed by employing the iterative multiscale diffusion on the wavelet coefficients. With a tuning diffusion threshold strategy, the proposed method can improve the image quality for both visualization and auto-segmentation applications. We validate our method using synthetic speckle images and real ultrasonic images. Performance improvement over other despeckling filters is quantified in terms of noise suppression and edge preservation indices.


New transgenic evidence for a system of sympathetic axons able to express tissue plasminogen activator (t-PA) within arterial/arteriolar walls.
Sympathetic axons embedded in a few arterioles and vasa vasora were recently shown to store tissue plasminogen activator (t-PA) in vesicles. But the extension of such t-PA axons to arteries and arterioles throughout the organism has not been verified. Confirmation of this anatomy would identify a second significant source of vessel wall t-PA. To visualize fine embedded axons independent of endothelium, we created a transgenic mouse whose expressions of the t-PA promoter and enhanced green fluorescent protein are confined to sympathetic neurons and other neural crest derivatives. Confocal images reveal the extension of t-PA axons to arterioles serving heart, brain, kidney, lung, mesentery, and skin; plus aortic, carotid, and mesenteric artery walls. Ganglion neurons and adrenal chromaffin cells also show strong expressions. These new sightings confirm the existence of a system of t-PA axons that is prominent in arterioles, and compatible with the release of neural t-PA into their walls.


Bactericidal activity of metal-mediated peroxide-ascorbate systems.
Model systems containing ascorbate, hydrogen peroxide, and divalent copper or cobalt have been shown to possess marked bactericidal activity. At equivalent concentrations, copper-containing systems were more bactericidal than the corresponding mixtures containing cobalt. Cobalt at concentrations below 10(-4) M did not appreciably augment microbicidal activity, whereas systems containing copper at concentrations as low as 5 x 10(-6) M were still capable of causing some bacterial death. Manganese was inactive. None of these systems was as potent as the well known myeloperoxidase-peroxide-halide system. The mechanisms of action of these systems are not as yet clear. The possibility that they function through the generation of superoxide (O(2) (-)), hydroxyl radical (OH.), or other free radicals was explored through the use of superoxide dismutase and several free radical scavengers. It seems likely at present that the two active metal-mediated systems function via separate mechanisms. The copper system acts with dehydroascorbate, whereas the cobalt system does not. Activity in the cobalt system appears to depend upon the generation of free radicals.


Multi- and Transgenerational Effects of Environmental Toxicants on Mammalian Reproduction.
Environmental toxicants (ETs) are an exogenous chemical group diffused in the environment that contaminate food, water, air and soil, and through the food chain, they bioaccumulate into the organisms. In mammals, the exposure to ETs can affect both male and female fertility and their reproductive health through complex alterations that impact both gametogeneses, among other processes. In humans, direct exposure to ETs concurs to the declining of fertility, and its transmission across generations has been recently proposed. However, multi- and transgenerational inheritances of ET reprotoxicity have only been demonstrated in animals. Here, we review recent studies performed on laboratory model animals investigating the effects of ETs, such as BPA, phthalates, pesticides and persistent contaminants, on the reproductive system transmitted through generations. This includes multigenerational effects, where exposure to the compounds cannot be excluded, and transgenerational effects in unexposed animals. Additionally, we report on epigenetic mechanisms, such as DNA methylation, histone tails and noncoding RNAs, which may play a mechanistic role in a nongenetic transmission of environmental information exposure through the germline across generations.


Arrestin2 expression selectively increases during neural differentiation.
Arrestins and G protein-coupled receptor kinases (GRKs) are key players in homologous desensitization of G protein-coupled receptors. Two non-visual arrestins, arrestin2 and 3, and five GRKs (GRK2, 3, 4, 5 and 6) are involved in desensitization of many receptors. Here, we demonstrate a steady increase in arrestin2 expression during prenatal development. The density of arrestin2 mRNA is higher in differentiated areas as compared with proliferative zones, whereas arrestin3 mRNA shows the opposite distribution. At embryonic day 14, concentrations of arrestin proteins are similar (32-34 nM). Later in development, arrestin2 expression rises, leading to a fourfold excess of arrestin2 over arrestin3 at birth (48 vs. 11 ng/mg protein or 102 vs. 25 nM). Among GRKs, only GRK5 increased with embryonic age from 124 nm at E14 to 359 nM at birth. Similarly, in vitro differentiation of cultured precursor cells, neurospheres, leads to a significant up-regulation of arrestin2 resulting in > 20-fold excess of arrestin2 (160 vs. 7 nM). GRK5 is the only subtype increased with neurosphere differentiation, although the change is only about twofold. The data demonstrate selective increases in the expression of arrestin2 associated with neural development and suggest specific yet unappreciated roles for arrestin2 in neural differentiation.


MicroRNA-376b-3p Suppresses Choroidal Neovascularization by Regulating Glutaminolysis in Endothelial Cells.
Choroidal neovascularization (CNV) is a common pathological change of various ocular diseases that causes serious damage to central vision. Accumulated evidence shows that microRNAs (miRNAs) are closely related with the regulation of endothelial metabolism, which plays crucial roles in angiogenesis. Here, we investigate the molecular mechanism underlying the regulation of endothelial glutamine metabolism by miR-376b-3p in the progression of CNV. Human retinal microvascular endothelial cells (HRMECs) were transfected with control or miR-376b-3p mimics, and the expression of glutaminase 1 (GLS1), a rate-limiting enzyme in glutaminolysis, was detected by real-time PCR or Western blotting. The biological function and glutamine metabolism of transfected HRMECs were measured by related kits. Luciferase reporter assays were used to validate the CCAAT/enhancer-binding protein beta (CEBPB) was a target of miR-376b-3p. Chromatin immunoprecipitation and RNA immunoprecipitation assays were performed to verify the binding of CEBPB on the promoter region of GLS1. Fundus fluorescein angiography and immunofluorescence detected the effect of miR-376b-3p agomir on rat laser-induced CNV. The expression of miR-376b-3p was decreased, whereas GLS1 expression was increased in the retinal pigment epithelial-choroidal complexes of rats with CNV. HRMECs transfected with miR-376b-3p mimic showed inhibition of CEBPB, resulting in the inactivation of GLS1 transcription and glutaminolysis. Moreover, the miR-376b-3p mimic inhibited proliferation, migration and tube formation but promoted apoptosis in HRMECs, whereas these effects counteracted by α-ketoglutarate supplementation or transfection with CEBPB overexpression plasmid. Finally, the intravitreal administration of the miR-376b-3p agomir restrained CNV formation. Collectively, miR-376b-3p is a suppressor of glutamine metabolism in endothelial cells that could be expected to become a therapeutic target for the treatment of CNV-related diseases.


Singlet oxygen generation from lophine hydroperoxides.
Singlet oxygen was detected from the reaction of lophine hydroperoxides 2 in the presence of 1,3-diphenyl-isobenzofuran as a singlet oxygen detector. In order to examine the substituent effect on the formation of (1)O(2), 2-(p-substituted phenyl) lophine peroxides 2a-c were tested. It was found that an electron-attracting group contributed to the efficient formation of (1)O(2) (80% for a NO(2) group), while an electron-donating group enhanced the efficiency of chemiluminescence.


Characterization of antigens recognized by monoclonal and polyclonal antibodies directed against uvomorulin.
Uvomorulin is a cell surface glycoprotein involved in compaction of early mouse embryo. Antibodies, either monoclonal or polyclonal, raised against a purified tryptic fragment of uvomorulin recognize, in a detergent lysate of embryonal carcinoma cells metabolically labeled with 35S, three molecules (120, 100, and 88 kDa) that are not related, as judged by peptide mapping. Only the 120-kDa form is related to the tryptic fragment of uvomorulin and, thus, is considered as the native form of uvomorulin. Although all three products are apparently detectable at the cell surface, only the 120-kDa form is glycosylated. Coimmunoprecipitation of the three different polypeptides is probably due to shared epitopes rather than to their presence in a multimeric complex.


Photocatalytic ozonation under visible light for the remediation of water effluents and its integration with an electro-membrane bioreactor.
Photocatalysis and photocatalytic ozonation under visible light have been applied for the purification of a complex aqueous matrix such as the grey water of Masdar City (UAE), by using N-doped brookite-rutile catalysts. Preliminary runs on 4-nitrophenol (4-NP) solutions allowed to test the reaction system in the presence of a model pollutant and to afford the relevant kinetic parameters of the process. Subsequently, the remediation of grey water effluent has been evaluated in terms of the reduction of total organic carbon (TOC) and bacterial counts. The concentration of the most abundant inorganic ionic species in the effluent has been also monitored during reaction. Photocatalytic ozonation under visible light allowed to reduce the TOC content of the grey water by ca. 60% in the optimized experimental conditions and to reduce the total bacterial count by ca. 97%. The extent of TOC mineralization reached ca. 80% when the photocatalytic ozonation occurred downstream to a preliminary electro-membrane bioreactor (eMBR). Coupling the two processes enhanced the global efficiency. In fact, the eMBR treatment lowered the turbidity and the organic load of the effluent entering the photocatalytic ozonation treatment, which in turn enhanced the extent of purification and disinfection.


Lenvatinib as a Therapeutic Option in Unresectable Metastatic Pheochromocytoma and Paragangliomas.
Metastatic pheochromocytomas and paragangliomas (mPPGL) are rare vascular neuroendocrine tumors that highly express vascular growth factors. Systemic treatment options in cases of unresectable multisite disease are limited. Multikinase inhibitors that inhibit angiogenesis, such as lenvatinib, have proven effective in several other malignancies, and may be a viable option for mPPGL. We aimed to evaluate the efficacy of lenvatinib as salvage therapy in mPPGLs. This was a retrospective analysis of mPPGL patients ≥ 18 years of age who received lenvatinib from 2015 to 2020 at a tertiary referral center. Patients were started on lenvatinib 20 mg daily and dose was adjusted according to tolerance or disease progression. Eleven patients were included. Median treatment duration was 14.7 months (95% CI, 2.3-NE). Treatment was discontinued due to disease progression, adverse events, or death. Overall survival at 12 months was 80.8% (95% CI, 42.3-94.9%) but its median was not reached. Median progression-free survival was 14.7 months (95% CI, 1.7-NE). Among the 8 patients with measurable disease, overall response rate was 63%, as 5/8 experienced a partial response and 3/8 had stable disease. Worsening hypertension and anemia were the most common adverse events. Lenvatinib may be a viable treatment option for mPPGL, although at the potential risk of worsening hypertension. Larger, multicenter studies are needed to better characterize treatment efficacy.


Functional internal complexity of amygdala: focus on gene activity mapping after behavioral training and drugs of abuse.
The amygdala is a heterogeneous brain structure implicated in processing of emotions and storing the emotional aspects of memories. Gene activity markers such as c-Fos have been shown to reflect both neuronal activation and neuronal plasticity. Herein, we analyze the expression patterns of gene activity markers in the amygdala in response to either behavioral training or treatment with drugs of abuse and then we confront the results with data on other approaches to internal complexity of the amygdala. c-Fos has been the most often studied in the amygdala, showing specific expression patterns in response to various treatments, most probably reflecting functional specializations among amygdala subdivisions. In the basolateral amygdala, c-Fos expression appears to be consistent with the proposed role of this nucleus in a plasticity of the current stimulus-value associations. Within the medial part of the central amygdala, c-Fos correlates with acquisition of alimentary/gustatory behaviors. On the other hand, in the lateral subdivision of the central amygdala, c-Fos expression relates to attention and vigilance. In the medial amygdala, c-Fos appears to be evoked by emotional novelty of the experimental situation. The data on the other major subdivisions of the amygdala are scarce. In conclusion, the studies on the gene activity markers, confronted with other approaches involving neuroanatomy, physiology, and the lesion method, have revealed novel aspects of the amygdala, especially pointing to functional heterogeneity of this brain region that does not fit very well into contemporarily active debate on serial versus parallel information processing within the amygdala.


Thermal therapy for congestive heart failure: estimation by TEI index.
Systolic dysfunction commonly coexists with diastolic dysfunction in patients with congestive heart failure due to myocardial disease. Also, right ventricular dysfunction is frequently associated with left ventricular dysfunction. The Doppler total ejection isovolume (TEI) index, a combined measurement of systolic and diastolic myocardial performance, is more reflective of overall cardiac function than systolic or diastolic function alone in both ventricles, and provides a conceptually new measure of global cardiac function. Single sauna bathing improves acute hemodynamics and repeated sauna therapy improves cardiac function and clinical symptoms in patients with heart failure. More recently, improvement of vascular endothelial function were observed by repeated sauna therapy in patients with heart failure. The TEI index, combining systolic and diastolic myocardial function, is a promising tool for the quantitative assessment of global cardiac function before and after thermal therapy.


Altered expression of CDX2 in colorectal cancers.
CDX2 is a caudal-related homeobox transcription factor whose expression in the adult is normally restricted to the intestinal epithelium; it is implicated in the development and maintenance of the intestinal mucosa. The specific aim of this study was to elucidate the potential etiological role of CDX2 protein in colorectal carcinogenesis. We have analyzed the expression pattern of CDX2 protein in relation to the phenotype of 123 sporadic colorectal cancers by immunohistochemistry using tissue microarray. Strong CDX2 immunostaining was seen in the nuclei of corresponding normal intestinal epithelium. Interestingly, loss of CDX2 immunostaining was observed in 29 (23.6%) of 123 colorectal adenocarcinomas and its expression was correlated with the differentiation grade of the carcinoma (Chi-Square test, p<0.01). Clinically, CDX2 protein was immunopositive in 11 (91.7%) of 12 cases corresponding to stage A, 40 (85.1%) of 47 corresponding to stage B, 39 (69.6%) of 56 corresponding to stage C, and 4 (50.0%) of 8 corresponding to stage D. Statistically, CDX2 protein expression was related to tumor stage (Bartholomew test, p<0.05) and lymph node metastasis (Chi-Square test, p<0.05). These results indicate that loss of expression of CDX2 protein may play an important role in the tumorigenesis of colorectal cancers and that CDX2 expression represents a highly significant marker, which is able to identify a subset of patients at high risk.


[A case of recurring breast cancer causing pericardial metastasis showing a good response following local treatment with methotrexate].
A 52-year-old woman was admitted with a chief complaint of dyspnea. She had undergone right mastectomy for Stage IIB breast cancer 2 years and five months earlier. Chest roentgenogram revealed cardiomegaly and bilateral pleural effusion, and a cardiac echogram showed marked retention of pericardial effusion. A diagnosis of cardiac tamponade was made and pericardiocentesis for continuous drainage was carried out cytologically, the effusion was class V and showed evidence of pericardial metastasis of breast cancer. Pericardiocentesis followed by methotrexate instillation 6 times in a dose of 110 mg successfully controlled the cardiac tamponade, after which the catheter could be removed from the pericardial space. Systemic chemotherapy (CEF) was started at the same time. The patient was discharged very much improved after these treatments, but she died of brain metastasis after 9 months. This case suggests that intrapericardial application of methotrexate may be very useful in the management of carcinomatous cardiac tamponade without any serious side effects.


Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity.
Patients with active acromegaly have increased bone turnover and skeletal abnormalities. Biochemical cure of acromegaly may represent a functional GH-deficient state and result in cortical bone loss. Reduced PTH target-organ sensitivity occurs in adult GH deficiency and may underlie the associated development of osteoporosis. We examined the effect of active and treated acromegaly on PTH concentration and target-organ sensitivity. Ten active acromegalic subjects (GH nadir > 0.3 mug/liter after 75-g oral glucose load and IGF-I above age-related reference range) and 10 matched controls participated in the study. Half-hourly blood and 3-h urine samples were collected on patients and controls for 24 h. Samples were analyzed for PTH, calcium (Ca), nephrogenous cAMP (NcAMP, a marker of PTH renal activity), beta C-telopeptide (bone resorption marker), and procollagen type-I amino-terminal propeptide (bone formation marker). Serum calcium was adjusted for albumin (ACa). Eight acromegalic subjects who achieved biochemical cure (GH nadir < 0.3 mug/liter after 75-g oral glucose load and IGF-I within reference range) after standard surgical and/or medical treatment reattended and the protocol repeated. Active acromegalic subjects had higher 24-h mean PTH, NcAMP, ACa, urine Ca, beta C-telopeptide, and procollagen type I amino-terminal propeptide (P < 0.05), compared with controls. Twenty-four-hour mean PTH increased (P < 0.001) in the acromegalic subjects after treatment, whereas NcAMP and ACa decreased (P < 0.05). Increased bone turnover associated with active acromegaly may result from increased PTH concentration and action. Biochemical cure of acromegaly results in reduced PTH target-organ sensitivity indicated by increased PTH with decreased NcAMP and ACa concentrations. PTH target-organ sensitivity does not appear to return to normal after successful treatment of acromegaly in the short term and may reflect functional GH deficiency.


"Trading bickering for teamwork".
Bickering is an unpleasant phenomena found wherever groups of people congregate. Bickering on a health care team such as that found in the nurse department can create a negative environment and poor morale. The nurse manager should take responsibility for action which can deter this type of behavior and should visibly lead the staff to more productive interactions.


Enantiomeric separation of some flavanones using shinorhizobial linear octasaccharides in CE.
Succinoglycan, a shinorhizobial exopolysaccharide produced by Shinorhizobium meliloti, is composed of an octasaccharide subunit. S. meliloti produces both high-molecular-weight and low-molecular-weight (M(r)<10 000) succinoglycans that consisted of monomer, dimer, or trimer of an octasaccharide unit. We isolated and purified the monomer among low-molecular-weight succinoglycans and used this microbial linear octasaccharide as a novel chiral additive for enantiomeric separation of some flavanones such as homoeriodictyol, hesperetin, naringenin, and isosakuranetin in CE. Throughout the present investigation, we firstly used noncyclic oligosaccharides for the chiral separation of flavanones. We also found that successful enantioseparation of four flavanones depends on the presence of succinate substituents of the linear monomeric octasaccharide in CE, suggesting that succinylation of succinoglycan monomer is decisive for the effective enantiomeric separation.


Quantification of protein-protein interactions within membranes by fluorescence correlation spectroscopy.
The characterization of interactions between membrane proteins as they take place within the lipid bilayer poses a technical challenge, which is currently very difficult and, in many cases, impossible to overcome. The recent development of a method based in the combination two-color fluorescence cross-correlation spectroscopy with scanning of the focal volume allows the detection and quantification of interactions between biomolecules inserted in biological membranes. This powerful strategy has allowed the quantitative analysis of diverse systems, such as the association between proteins of the Bcl-2 family involved in apoptosis regulation or the binding between a growth factor and its receptor during signaling. Here, we review the last developments to quantify protein/protein interactions in lipid membranes and focus on the use of fluorescence-correlation-spectroscopy approaches for that purpose.


Low ankle-brachial pressure index predicts increased risk of cardiovascular disease independent of the metabolic syndrome and conventional cardiovascular risk factors in the Edinburgh Artery Study.
To investigate whether a low ankle-brachial pressure index (ABI) predicts increased risk of cardiovascular disease (CVD) independent of the metabolic syndrome and conventional cardiovascular risk factors. The Edinburgh Artery Study is a population-based cohort study in which subjects were followed up until their death or for approximately 15 years. Low ABI at baseline was defined as <0.9; subjects with ABI >1.4 (n = 13) were excluded from the analyses. We used a modified version of the definition of the metabolic syndrome published in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, replacing waist circumference criteria with BMI criteria. Data on relevant parameters were available for 1,467 men and women ages 55-74 years at baseline. Cox proportional hazards models were used to study cardiovascular morbidity and mortality before and after adjusting for potential confounding factors. We determined that 25% of the study population had the metabolic syndrome and that a low ABI was more prevalent among people with than without the metabolic syndrome (24 vs. 15%; P < 0.001). During the follow-up period, there were 226 deaths from CVD and 462 nonfatal cardiovascular events. The hazard ratio (95% CI) for low ABI after adjusting for age, sex, baseline CVD, diabetes, smoking status, LDL cholesterol, and metabolic syndrome was 1.5 (1.1-2.1) for CVD mortality and 1.5 (1.2-1.8) for all CVD outcomes. Low ABI is associated with increased risk of CVD independent of the metabolic syndrome and other major CVD risk factors.


The Pentaflex pressure-reducing mattress replacement.
Support surfaces play a crucial role in pressure sore prevention. This article outlines the use of polyurethane foam as a versatile and effective support surface. It briefly describes a number of tests which are used to determine foam quality and summarizes the characteristics and clinical evidence supporting the use of the Pentaflex pressure-reducing foam mattress.


Ultrastructure of spermiogenesis and spermatozoa of Discocotyle sagittata (Monogenea: Polyopisthocotylea: Discocotylinea).
Ultrastructural analysis revealed that the spermatozoon of Discocotyle sagittata (Leuckart, 1842) is composed of two parallel axonemes, mitochondrion, nucleus and cortical microtubules. The nucleus, which occupies a central/distal position and has an unusual crescent-shaped profile, is slightly shorter than the mitochondrial rod. The two axonemes, which are of unequal length, and the cortical microtubules (up to 68 forming a continuous ring in the principal region) extend almost the entire length of the spermatozoon. A fold of the plasma membrane creates a unilateral flange or undulating membrane. Epifluorescence microscopy indicated that spermatogenesis gives rise to clusters of 64 spermatids connected to a common cytophore. Spermiogenesis and the structure of the filiform sperm of D. sagittata conform to the typical polyopisthocotylean pattern.


MyD88 Regulates LPS-induced NF-ĸB/MAPK Cytokines and Promotes Inflammation and Malignancy in Colorectal Cancer Cells.
Inflammation may play a role in cancer initiation and progression. The molecular mechanisms by which inflammation causes colorectal cancer, remains unclear. The present study investigated a signaling pathway that affects inflammation in colorectal cancer. SW480 cells, HCT116 cells, and cells with knockdown of myeloid differentiation 88 (MyD88), and forced expression of MyD88 were treated with lipopolysaccharide (LPS; 1 μg/ml). Inflammation-related mRNA expression was analyzed by the quantitative reverse transcription polymerase chain reaction and inflammatory cytokines were detected by western blotting. The enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammation-related cytokines in colorectal cancer cells. Cancer cell properties were evaluated using the wound-healing assay, transwell migration assay, transwell invasion assay, colony-formation assay, and CCK-8 assay. LPS up-regulated mRNA and protein levels of inflammatory factors in colorectal cancer cells. Knockdown of MyD88 inhibited LPS-induced mRNA expression and inflammatory protein expression in colorectal cancer cells. Similarly, silencing of MyD88 expression suppressed LPS-induced changes in the biological behavior of colorectal cancer cells. Silencing of MyD88 expression down-regulated expression of proteins of the LPS/nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-ĸB)/mitogen-activated protein kinase (MAPK) signaling pathway. Restoration of the expression of MyD88 reversed the effects in LPS-treated HCT116 cells. MyD88-regulated LPS/NF-ĸB/MAPK signaling pathway affects the inflammatory and biological behavior of LPS-induced colorectal cancer cells.


Automated graph-based analysis and correction of cortical volume topology.
The human cerebral cortex is topologically equivalent to a sheet and can be considered topologically spherical if it is closed at the brain stem. Low-level segmentation of magnetic resonance (MR) imagery typically produces cerebral volumes whose tessellations are not topologically spherical. We present a novel algorithm that analyzes and constrains the topology of a volumetric object. Graphs are formed that represent the connectivity of voxel segments in the foreground and background of the image. These graphs are analyzed and minimal corrections to the volume are made prior to tessellation. We apply the algorithm to a simple test object and to cerebral white matter masks generated by a low-level tissue identification sequence. We tessellate the resulting objects using the marching cubes algorithm and verify their topology by computing their Euler characteristics. A key benefit of the algorithm is that it localizes the change to a volume to the specific areas of its topological defects.


CXCL12 defines lung endothelial heterogeneity and promotes distal vascular growth.
There is a growing amount of data uncovering the cellular diversity of the pulmonary circulation and mechanisms governing vascular repair after injury. However, the molecular and cellular mechanisms contributing to the morphogenesis and growth of the pulmonary vasculature during embryonic development are less clear. Importantly, deficits in vascular development lead to significant pediatric lung diseases, indicating a need to uncover fetal programs promoting vascular growth. To address this, we used a transgenic mouse reporter for expression of Cxcl12, an arterial endothelial hallmark gene, and performed single-cell RNA sequencing on isolated Cxcl12-DsRed+ endothelium to assess cellular heterogeneity within pulmonary endothelium. Combining cell annotation with gene ontology and histological analysis allowed us to segregate the developing artery endothelium into functionally and spatially distinct subpopulations. Expression of Cxcl12 is highest in the distal arterial endothelial subpopulation, a compartment enriched in genes for vascular development. Accordingly, disruption of CXCL12 signaling led to, not only abnormal branching, but also distal vascular hypoplasia. These data provide evidence for arterial endothelial functional heterogeneity and reveal conserved signaling mechanisms essential for pulmonary vascular development.


Soft nanostructured films for directing the assembly of functional materials.
Lipids are a class of biological small molecules with hydrophilic and hydrophobic constituents forming the structural membranes in cells. Over the past century an extensive understanding of lipid biology and biophysics has been developed illuminating lipids as an intricate, highly tunable, and hierarchical soft-matter system. In addition to serving as cell membrane models, lipids have been investigated as microphase separated structures in aqueous solutions. In terms of applications lipids have been realized as powerful structural motifs for the encapsulation and cellular delivery of genetic material. More recently, lipids have also revealed promise as thin film materials, exhibiting long-range periodic nano-scale order and tunable orientation. In this review we summarize the pertinent understanding of lipid nanostructure development in bulk aqueous systems followed by the current and potential perturbations to these results induced by introduction of a substrate. These effects are punctuated by a summary of our published results in the field of lipid thin films with added nucleic acids and key results introducing hard materials into lipid nanostructured substrates.


[Diabetes mellitus and Friedreich´s ataxia in a child: a complicated coexistence].
Friedreich's ataxia is an autosomal recessive disease caused by trinucleotide repeat expansion, presenting among other systemic complications, diabetes mellitus. The appearance of motor clumsiness, with running and jumping difficulties in a 6-year-old boy prompted the genetic study of Friedreich's ataxia, confirming his diagnosis. After diagnosis, it was evaluated by Pediatric Cardiology, detecting the presence of non-obstructive hypertrophic cardiomyopathy, and by Pediatric Endocrinology, due to overweight. At 9 years of age, he was diagnosed with diabetes mellitus, a regimen of insulin treatment was initiated. During follow-up, he presented significant neurological deterioration, reaching the use of a wheelchair, which hinders adequate metabolic control. This is a report of a pediatric patient with Friedrich ataxia and diabetes mellitus.


Factor structure of Bech's version of the Brief Psychiatric Rating Scale in Brazilian patients.
The objective of the present study was to evaluate the factor structure of Bech's version of the Brief Psychiatric Rating Scale (BPRS), translated into Portuguese. The BPRS was administered to a heterogeneous group of psychiatric inpatients (N = 98) and outpatients (N = 62) in a University Hospital. Each patient was evaluated from one to eight times. The interval between consecutive interviews was one week for the inpatients and one month for the outpatients. The results were submitted to factorial analysis. The internal consistency of the total scale and of each factor was also estimated. Factorial analysis followed by normalized orthogonal rotation (Varimax) yielded four factors: Withdrawal-Retardation, Thinking Disorder, Anxious-Depression and Activation. Internal consistency measured by Cronbach's alpha coefficient ranged from 0.766 to 0.879. The data show that the factor structure of the present instrument is similar to that of the American version of the BPRS which contains 18 items, except for the absence of the fifth factor of the latter scale, Hostile-Suspiciousness.


Use of complementary and alternative medicine by patients with cancer in northern Turkey: analysis of cost and satisfaction.
The aims of this study were to determine (1) the prevalence of complementary and alternative medicine use among patients with cancer, (2) the method of use of the particular therapy, (3) the reasons for using complementary and alternative medicine therapies, (4) the benefits experienced by the use of complementary and alternative medicine, (5) the source of information about complementary and alternative medicine therapies and, (6) the satisfaction and cost of complementary and alternative medicine. Complementary and alternative medicine consists of diverse medical and healthcare systems, practices and products that are not considered at present to be a part of conventional medicine. The majority of patients who use complementary and alternative medicine use more than one method. Complementary and alternative medicine use is more common in cases of advanced disease or poor prognosis. This is a descriptive study of complementary and alternative medicine. This study was conducted in the Chemotherapy Unit at Ondokuz Mayıs University, Faculty of Medicine, Samsun, Turkey, between 18 March 2008-30 June 2008. Two hundred fifty-three patients with cancer, among 281 patients who applied to the chemotherapy clinic between these dates, agreed to take part in the study with whom contact could be made were included. A questionnaire including descriptive characteristics in collecting data, characteristics about diseases and their treatments, complementary and alternative medicine information and implementation situations and a control list about complementary and alternative medicine implementations were given. The collected data were evaluated by computer using descriptive statistics, the chi-square test and Student's t-test. In this study, 94·1% of the patients were content with medical treatment, 58·9% of them used complementary and alternative medicine treatments, 41·1% did not use any complementary and alternative medicine treatments. The satisfaction level of the patients with complementary and alternative medicine methods was slightly above mediocre (2·33 SD 0·64, on a scale of 1-3). The average cost per capita spent by the patients using complementary and alternative medicine for all the different methods was US$288·26. It was determined that although patients did not have enough knowledge about complementary and alternative medicine methods, the prevalence of complementary and alternative medicine and satisfaction levels are high that complementary and alternative medicine users spend substantial sums of money for these methods. To sustain medical treatment and prognosis of cancer, it is important for nurses to consult with their patients regarding the use and potential risks of some complementary and alternative medicine.


Plasma leptin is independently associated with the intima-media thickness of the common carotid artery.
To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is significantly and independently associated with plasma concentrations of leptin, an adipose tissue hormone that has recently been proposed as a cardiovascular risk factor in obese patients. Cross-sectional sample of normal-weight and obese men and women. One-hundred and twenty healthy subjects (52 men and 68 women), aged 18-45 y and with a wide range of BMI, were recruited for the study. Fasting plasma leptin concentrations and the IMT of the CCA were measured in all subjects. Leptin concentrations were measured by radioimmunoassay and the IMT of the CCA was quantified by high resolution B-mode ultrasound imaging. Central fat (measured by waist circumference), smoking habits, blood pressure, insulin sensitivity (measured by the insulin tolerance test), and fasting plasma glucose, insulin and lipid pattern (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) were also measured. IMT of the CCA was positively correlated with log leptin concentrations (P<0.005 in men and P<0.001 in women), body mass index (P<0.001 in men and women), waist circumference (P<0.001 in men and women), age (P<0.001 in men and P<0.05 in women), and negatively associated with insulin sensitivity in both sexes (P<0.05). IMT was also directly correlated with cholesterol (P<0.05), LDL-cholesterol (P<0.01) and systolic blood pressure in men (P<0.05), and with diastolic blood pressure levels in women (P<0.05). When a multiple linear regression model was used without body mass index (BMI), the correlation between leptin and IMT was maintained in both men (P<0.01) and women (P<0.005), independent of age, insulin sensitivity, smoking habits, systolic blood pressure, fasting glucose, triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol. By contrast, BMI-adjusted leptin concentrations were not significantly associated with IMT (Pc (partial correlation): 0.41 in men and 0.15 in women). Moreover, when BMI was entered into a multiple linear regression model without leptin, the correlation between BMI and IMT was maintained in both men (P<0.005) and women (P<0.01), independent of the same parameters. Plasma leptin concentrations are independently associated with the IMT of the CCA, suggesting that the increase of adipose tissue mass (or leptin per se) may have an unfavourable influence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent and/or confounded by the relationship between IMT and obesity.


Influence of Educational Level and Healthy Habits on the Prevalence of Diabesity in a Spanish Working Population.
Diabesity is a growing problem internationally. Taking into account the importance of physical activity and diet in its prevention and treatment, the objective of this study was to delve into the impact of healthy habits on diabesity. A descriptive, cross-sectional study was carried out in 386,924 Spanish adult workers. Obesity was determined according to eleven different formulas. Life habits were also valued; sociodemographic variables; and educational level; as well as analytical and clinical variables such as blood pressure and blood glucose levels. The association between the different variables was performed using the chi-square and the Student's t-tests when the samples were independent. A multivariate analysis was performed using the multinomial logistic regression test by calculating the odds ratio and a 95% confidence interval. The Hosmer-Lemeshow goodness-of-fit test was also performed. The overall prevalence of diabesity ranged between 0.3% (95% CI 0.3-0.4) when obesity was assessed according to the abdominal volume index and 8.3% (95% CI 8.2-8.4) when evaluated according to the CUN-BAE (Clínica Universitaria de Navarra Body Adiposity Estimator) formula. The prevalence of diabesity was also higher in workers with a non-heart-healthy diet and in those who did not exercise regularly. The most disadvantaged socioeconomic classes are those with the highest prevalence of diabesity. It is important to prioritise prevention in populations and communities with the most unfavourable social and environmental conditions to reduce the burden of diabesity.


Staging and response of sternal histoplasmosis by 18F-FDG PET/CT.
Histoplasmosis, a granulomatous mycosis caused by the fungus Histoplasma capsulatum, is known to primarily affect the lungs and the immune system, with involvement of skeletal system as a rare manifestation, in which case the disease usually assumes multifocality. We present a singular case of a young man diagnosed to have an isolated skeletal histoplasmosis involving the body of sternum where 18F-FDG PET/CT played major role in both diagnosis and in response evaluation to antifungal therapy.


Animal Models of Temporomandibular Disorder.
Temporomandibular disorders (TMD) are a group of diseases in the oral and maxillofacial region that can manifest as acute or chronic persistent pain, affecting millions of people worldwide. Although hundreds of studies have explored mechanisms and treatments underlying TMD, multiple pathogenic factors and diverse clinical manifestations make it still poorly managed. Appropriate animal models are helpful to study the pathogenesis of TMD and explore effective treatment measures. At present, due to the high cost of obtaining large animals, rodents and rabbits are often used to prepare TMD animal models. Over the past decade, various animal models have been intensively developed to understand neurobiological and molecular mechanisms of TMD, and seek effective treatments. Although these models cannot carry out all clinical features, they are valuable in revealing the mechanisms of TMD and creating curative access. Currently, there are multitudinous animal models of TMD research. They can be constructed in different means and summarized into four ways according to the various causes and symptoms, including chemical induction (intra-articular injection of ovalbumin, collagenase, formalin, vascular endothelial growth factor, intramuscular injection of complete Freund's adjuvant, etc.), mechanical stress stimulation (passive mouth opening, change of chewing load), surgical operation (partial disc resection, joint disc perforation) and psychological stress induction. Here, we summarize and discuss different approaches of animal models for determining neurophysiological and mechanical mechanisms of TMD and assess their advantages and limitations, respectively.


[Clinical, metabolic and hormonal changes in patients with obesity on low-calorie diet therapy].
Low-calorie diet therapy (LCDT) was used to treat obesity in 74 females aged 18-49 in four regimens: short-term (up to 7 days), of middle duration (10-14 days), long-term (up to 21-24 days) and fractionated. Middle duration of LCDT proved most favourable. Long-term fasting may bring unstable effects or complications. LCDT results in electrolyte unbalance, hypokalemia, hypokaligestia. Relevant correction is necessary on the diet day 5-6. Red cell count, blood levels of sugar and protein, lipidogram, nitrogenous metabolism, coagulation activity changed insignificantly. Obese patients on LCDT exhibited reduced hyperinsulinism responsible for body mass decrease, hyperproduction of hydrocortisone and prolactin enhancing fat synthesis. They also developed T3-hypothyrosis reducing thermogenesis. The changes in the body mass depended on these factors.


An optrode particle geometry to decrease response time.
A hollow 3 μm sensing microcapsule containing chromoionophores within a 100 nm organosilica shell is reported. This shows a response to an ion step two orders of magnitude faster than 'filled' sensing particles of similar diameter. Incorporation of chromoionophores ETH 5294 and ETH 7061 in the capsule shell is shown with a t(90) response <2 s compared with >15 min for filled particles of similar diameters. This ultrafast geometry is also extended to dual ionophore dye incorporation and preliminary exploration of a FRET-based ratiometric method is examined to extend the pH response range, using a single excitation wavelength.