Influence of organosulphur compounds from garlic on the secretion of matrix metalloproteinases and their inhibitor TIMP-1 by cultured HUVEC cells.
Organosulphur compounds from garlic, especially diallyl disulphide (DADS) at non-toxic concentrations, affected production and secretion of some matrix metalloproteinases (MMPs) and of tissue inhibitor of metalloproteinase-1 (TIMP-1), one of their inhibitors, by human umbilical vein endothelial cells. Addition of DADS to the culture medium resulted in a concentration-dependent reduction of secreted MMP-2 protein and activity as well as TIMP-1 protein. In the presence of inducers (phorbol 12-myristate 13-acetate, forskolin and tumor necrosis factor alpha) addition of DADS caused a distinct concentration-dependent decrease of MMP-9 and TIMP-1 secretion, while not affecting MMP-9 mRNA levels. Intracellular protein levels remained low and were not affected. Other organosulphur compounds like allyl mercaptan and S-allylcysteine showed no or less clear effects on MMP-secretion or TIMP-1-secretion. These results suggest that DADS may mediate some of the biological effects ascribed to garlic preparations through affecting MMP-TIMP balance.


Raised expression of APRIL in Chinese children with acute lymphoblastic leukemia and its clinical implications.
This study was to determine the expression of a proliferation-inducing ligand (APRIL) and its receptors, B-cell maturation antigen (BCMA) and transmembrane activator and calcium-modulating cyclophilin ligand interactor in childhood acute lymphoblastic leukemia (ALL). The correlation between the plasma APRIL levels and clinical status was also evaluated. Plasma samples from 20 untreated children with ALL, 23 children with ALL in remission, and 15 normal controls were assayed for APRIL plasma concentration by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction was performed to determine the mRNA expression of APRIL and its receptors in blood mononuclear cells in 20 untreated ALL children and 15 normal controls. The untreated ALL patients had higher plasma APRIL levels than the remission group and the normal controls (P<0.001, respectively). No significant difference was found between the remission group and the normal controls in the plasma APRIL levels (P=0.339). The plasma APRIL levels in the untreated patients correlated with white blood cell count at diagnosis (P=0.002) and risk category (P=0.013). The mRNA expression of both APRIL and BCMA in blood mononuclear cells of the ALL patients were higher than those of the normal controls (both P<0.001). No significant difference was found between the patients and the normal controls in the transmembrane activator and calcium-modulating cyclophilin ligand interactor expression (P>0.05). These findings indicate that APRIL and BCMA are over expressed in untreated ALL children. The levels of APRIL correlate with the progression of childhood ALL, which may provide certain clues for monitoring ALL clinically.


[Hemolytic disease of neonates due to anti-M: report of one case and review of reports of 21 cases].
To analyze and summarize clinical manifestation of hemolytic disease of the newborn (HDN) due to anti-M. Data of one case of HDN due to anti-M and the reports of 21 cases seen in the past 20 years at the home country were reviewed and analyzed. There was an increasing number of reports of cases with HDN due to anti-M. Among the 22 cases, four were the first fetus. Of 18 infants, ten were male, and eight were female. The blood group was MN in 19/21 infants, and was M in 2/21 infants. The blood group was N in 10/21 mothers, and was NN in 11/21 mothers. Among the 18 infants, the direct antiglobulin test of 7 infants were positive, of 4 infants were dubiously positive, and of 7 infants was negative. Among the 16 infants, the antibody release test of 13 infants was positive, and of 3 infants were negative. Among 17 infants, the free antibody test of all was positive. Among the 21 mothers, the anti-M of IgG were positive in all mothers, and along with IgM in 11 mothers. The anti-M of IgG was positive in all infants. Mild or severe anemia and icterus were found in all cases. Among the 15 cases, jaundice was evident on the 1st day of life in 11 cases. Among 13 cases, marked elevation of both indirect- and direct-reacting bilirubin levels was reported in 4 cases. Phototherapy was applied when jaundice became evident. High-dose intravenous immunoglobulin was given to 4/15 cases. Exchange transfusion were performed in 8 of 22 cases. Three cases died, and 19 cases were cured. HDN of varying degrees of severity has been reported in association with anti-M and can even lead to intrauterine deaths or requiring treatment with exchange transfusion. If the mother has a history of prior intrauterine deaths, abortion, hydrops fetalis, severe fetal anemia or infertile, MN blood group and anti-M antibodies should be tested after excluding the possibility of other causes and HDN due to ABO or Rh blood group incompatibility. As the efficacy of phototherapy increases, the role of exchange transfusion in acute management is rapidly decreasing. High-dose intravenous immunoglobulin and/or intramuscular metalloporphyrins may further reduce the need for exchange transfusion. The exchange transfusion may be performed through peripheral arterial (drawn out) and venous (infused in) lines.


Strategies for discovery and improvement of enzyme function: state of the art and opportunities.
Developments in biocatalysis have been largely fuelled by consumer demands for new products, industrial attempts to improving existing process and minimizing waste, coupled with governmental measures to regulate consumer safety along with scientific advancements. One of the major hurdles to application of biocatalysis to chemical synthesis is unavailability of the desired enzyme to catalyse the reaction to allow for a viable process development. Even when the desired enzyme is available it often forces the process engineers to alter process parameters due to inadequacies of the enzyme, such as instability, inhibition, low yield or selectivity, etc. Developments in the field of enzyme or reaction engineering have allowed access to means to achieve the ends, such as directed evolution, de novo protein design, use of non-conventional media, using new substrates for old enzymes, active-site imprinting, altering temperature, etc. Utilization of enzyme discovery and improvement tools therefore provides a feasible means to overcome this problem. Judicious employment of these tools has resulted in significant advancements that have leveraged the research from laboratory to market thus impacting economic growth; however, there are further opportunities that have not yet been explored. The present review attempts to highlight some of these achievements and potential opportunities.


Scale-up of polymerization processes.
Scale-up and/or scale-down procedures are crucial during the development of chemical processes. These procedures should be integrated to form a multidisciplinary approach encompassing several branches of science and engineering. The challenge is to find a balance between chemistry, design, environment, hygiene and safety (EHS) compliance and economic factors. The iterative process of scale-up procedures also requires concept discrimination at early stages of process development. Scale-up studies should predict the reactor behavior and the quality and properties of a product from laboratory and pilot plant to full scale; however, not every pilot scale presents a valid industrial scaled-down size. A rational mathematical model describing the process reasonably well for large scale is important for designing industrial processing units, but this is only feasible if a phenomenological understanding is achieved, and if the necessary constants and parameters are estimated accurately. An accomplished process development procedure must lead to products presenting the same properties at both small and large scale.


BMP type II receptor deficiency confers resistance to growth inhibition by TGF-β in pulmonary artery smooth muscle cells: role of proinflammatory cytokines.
Mutations in the bone morphogenetic protein (BMP) type II receptor (BMPR-II) underlie most cases of heritable pulmonary arterial hypertension (HPAH) and a significant proportion of sporadic cases. Pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) not only exhibit attenuated growth suppression by BMPs, but an abnormal mitogenic response to transforming growth factor (TGF)-β1. We sought to define the mechanism underlying this loss of the antiproliferative effects of TGF-β1 in BMPR-II-deficient PASMCs. The effect of TGF-β1 on PASMC proliferation was characterized in three different models of BMPR-II dysfunction: 1) HPAH PASMCs, 2) Bmpr2(+/-) mouse PASMCs, and 3) control human PASMCs transfected with BMPR-II small interfering RNA. BMPR-II reduction consistently conferred insensitivity to growth inhibition by TGF-β1. This was not associated with altered canonical TGF-β1/Smad signaling but was associated with a secreted factor. Microarray analysis revealed that the transcriptional responses to TGF-β1 differed between control and HPAH PASMCs, particularly regarding genes associated with interleukins and inflammation. HPAH PASMCs exhibited enhanced IL-6 and IL-8 induction by TGF-β1, an effect reversed by NF-κB inhibition. Moreover, neutralizing antibodies to IL-6 or IL-8 restored the antiproliferative effect of TGF-β1 in HPAH PASMCs. This study establishes that BMPR-II deficiency leads to failed growth suppression by TGF-β1 in PASMCs. This effect is Smad-independent but is associated with inappropriately altered NF-κB signaling and enhanced induction of IL-6 and IL-8 expression. Our study provides a rationale to test anti-interleukin therapies as an intervention to neutralize this inappropriate response and restore the antiproliferative response to TGF-β1.


Characterizing the transcriptome and microsatellite markers for almond (Amygdalus communis L.) using the Illumina sequencing platform.
The almond tree (Prunus amygdalus Batsch) is an important nut tree grown in subtropical regions that produces nutrient-rich nuts. However, a paucity of genomic information and DNA markers has restricted the development of modern breeding technologies for almond trees. In this study, almonds were sequenced with Illumina paired-end sequencing technology to obtain transcriptome data and develop simple sequence repeats (SSR) markers. We generated approximately 64 million clean reads from the various tissues of mixed almonds, and a total of 42,135 unigenes with an average length of 988 bp were obtained in the present study. A total of 27,586 unigenes (57.7% of all unigenes generated) were annotated using several databases. A total of 112,812 unigenes were annotated with the Gene Ontology (GO) database and assigned to 82 functional sub-groups, and 29,075 unigenes were assigned to the KOG database and classified into 25 function classifications. There were 9470 unigenes assigned to 129 Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways from five categories in the KEGG pathway database. We further identified 8641 SSR markers from 48,012 unigenes. A total of 100 SSR markers were randomly selected to validate quality, and 82 markers could amplify the specific products of A. communis L., whereas 70 markers were successfully transferable to five species (A. ledebouriana, A. mongolica, A. pedunculata, A. tangutica, and A. triloba). Our study was the first to produce public transcriptome data from almonds. The development of SSR markers will promote genetics research and breeding programmes for almonds.


Nitroreductase-based GDEPT.
Nitroreductases that metabolise aromatic nitro groups to hydroxylamines are attractive as enzymes for GDEPT because of the very large electronic change that this metabolism generates, providing an efficient switch that can be exploited to generate potent cytotoxins. While nitroreductase enzymes are widespread, nearly all the work using these in GDEPT has been with the nfsB gene product of Escherichia coli, an oxygen-insensitive flavin mononucleotide nitroreductase (NTR). Four classes of prodrugs for NTR have been described; dinitroaziridinylbenzamides, dinitrobenzamide mustards, 4-nitrobenzylcarbamates and nitroindolines. While some quinones are excellent substrates for NTR, none have been identified as potential GDEPT prodrugs. The most widely studied prodrug used for GDEPT in conjunction with NTR is the dinitroaziridinylbenzamide CB 1954. This shows high selectivity (>1000-fold) in cell lines transfected with NTR, has potent and long-lasting inhibition of NTR-transfected tumours in mice, and is in Phase I trial in conjunction with virally-delivered NTR enzyme. The related mustard SN 23862 has similar selectivity and superior bystander effects in animal models. Nitrobenzyl carbamates of a variety of cytotoxic amines (including aniline mustards, enediynes, duocarmycin analogues, pyrrolobenzodiazepines and the antitumour antibiotics doxorubicin, actinomycin D and mitomcyin C) are metabolised efficiently by NTR to the hydroxylamines, that fragment to release the amines. Nitroindoline derivatives of duocarmycins also show moderate selectivity for NTR-transfected cell lines in culture.


Intestinal preconditioning is mediated by a transient increase in nitric oxide.
The effect of ischemic preconditioning on the intestine, as well the implantation of nitric oxide and prostacyclin in this process has been evaluated. Thus, intestinal ischemia-reperfusion was induced in rats, and the protection conferred by previous preconditioning was evaluated. In addition, the effect of nitric oxide inhibition and the administration of nitric oxide were determined. Results show that the increases observed in LDH release after ischemia-reperfusion were prevented after preconditioning. Inhibition of nitric oxide synthesis abolished the protective effect of preconditioning, and nitric oxide administration replicated this effect. Also, an increased synthesis of nitric oxide has been detected after preconditioning. Increases in 6 keto PGF1 alpha were independent of nitric oxide. Altogether indicates that preconditioning is triggered by an initial increase in nitric oxide synthesis.


Addressing The Interlocking Impact Of Colonialism And Racism On Filipinx/a/o American Health Inequities.
Within the monolithic racial category of "Asian American," health determinants are often hidden within each subgroup's complex histories of indigeneity, colonialism, migration, culture, and socio-political systems. Although racism is typically framed to underscore the ways in which various institutions (for example, employment and education) disproportionately disadvantage Black/Latinx communities over White people, what does structural racism look like among Filipinx/a/o Americans (FilAms), the third-largest Asian American group in the US? We argue that racism defines who is visible. We discuss pathways through which colonialism and racism preserve inequities for FilAms, a large and overlooked Asian American subgroup. We bring to light historical and modern practices inhibiting progress toward dismantling systemic racial barriers that impinge on FilAm health. We encourage multilevel strategies that focus on and invest in FilAms, such as robust accounting of demographic data in heterogeneous populations, explicitly naming neocolonial forces that devalue and neglect FilAms, and structurally supporting community approaches to promote better self- and community care.


[Struma ovarii. Report of a malignant and a benign case].
Struma ovarii is a rare type of ovarian teratoma, composed entirely or in part of thyroid tissue. Malignant Struma ovarii were exceptional. We report one benign and one malignant cases of Struma ovarii. We insist upon their rarety and the difficulty of preoperatory diagnosis. Prognosis is good after surgery.


Anemia in older persons.
Anemia in older persons is commonly overlooked despite mounting evidence that low hemoglobin levels are a significant marker of physiologic decline. Using the World Health Organization definition of anemia (hemoglobin level less than 13 g per dL [130 g per L] in men and less than 12 g per dL [120 g per L] in women), more than 10 percent of persons older than 65 years are anemic. The prevalence increases with age, approaching 50 percent in chronically ill patients living in nursing homes. There is increasing evidence that even mild anemia is associated with increased morbidity and mortality. Anemia warrants evaluation in all older persons, except those at the end of life or who decline interventions. About one third of persons have anemia secondary to a nutritional deficiency, one third have anemia caused by chronic inflammation or chronic kidney disease, and one third have unexplained anemia. Nutritional anemia is effectively treated with vitamin or iron replacement. Iron deficiency anemia often is caused by gastrointestinal bleeding and requires further investigation in most patients. Anemia of chronic inflammation or chronic kidney disease may respond to treatment of the underlying disease and selective use of erythropoiesis-stimulating agents. The treatment of unexplained anemia is difficult, and there is little evidence that treatment decreases morbidity and mortality, or improves quality of life. Occasionally, anemia may be caused by less common but potentially treatable conditions, such as autoimmune hemolytic anemia, malignancy, or myelodysplastic syndrome.


Chemically modified polysulfone hollow fibers with vinylpyrrolidone having improved blood compatibility.
Hydrophilic polysulfone membranes (PVP-PSf) were prepared from polysulfone membranes covalently conjugated with polyvinylpyrrolidone (PVP) on the surface. The immobilized amount of vinylpyrrolidone on PVP-PSf membranes was controlled by the amount of vinylpyrrolidone monomer in the reaction solution and the reaction time. The PVP-PSf membranes were found to be the most hydrophilic membranes among the polysulfone and surface-modified polysulfone membranes prepared in this study. This is explained by the long hydrophilic side chain of polyvinylpyrrolidone on the PVP-PSf membranes which contributes to the hydrophilic wiper on the hydrophobic PSf membranes. It was found that PVP-PSf membranes gave lower protein adsorption from a plasma solution than polysulfone and other surface-modified membranes (p < 0.01). This is attributed to the hydrophilic surface of the PVP-PSf membranes, because the hydrophilic surface is known to reduce the protein adsorption on the membranes. The PVP-PSf membranes showed a much suppressed number of adhering platelets on the surface than polysulfone and other surface-modified membranes (p < 0.01). It is suggested that the hydrophilic surface of the PVP-PSf membranes without ionic groups causes the suppression of platelet adhesion on the PVP-PSf membranes and that the long hydrophilic side chain of polyvinylpyrrolidone on PVP-PSf membranes contributes to the hydrophilic and hemocompatible wipers on the surface of the hydrophobic PSf membranes.


Penetration of ampicillin ('Pondocillin') and amoxycillin ('Imacillin') into bronchial secretions.
The penetration of ampicillin and amoxycillin into bronchial secretions was investigated by bronchoscopy in 20 patients suffering from exacerbations of chronic bronchitis. Five patients received 500 mg pivampicillin, 8 received 700 mg pivampicillin and 7 received 500 mg amoxycillin. There were no significant differences between these three treatments in respect of the serum and bronchial secretion concentrations at the time of bronchoscopy, nor were there any significant differences in the peak serum level or total bioavailability of each regimen. The concentrations in bronchial secretions, on average, were 5.7%, 9.0% and 7.6% of the corresponding serum concentrations in patients given 500 mg pivampicillin, 700 mg pivampicillin and 500 mg amoxycillin, respectively. The concentration in bronchial secretions exceeded the MIC for sensitive strains of Haemophilus influenzae in more cases treated with pivampicillin than with amoxycillin.


Recent advances in central cardiovascular control: sex, ROS, gas and inflammation.
The central nervous system (CNS) in concert with the heart and vasculature is essential to maintaining cardiovascular (CV) homeostasis. In recent years, our understanding of CNS control of blood pressure regulation (and dysregulation leading to hypertension) has evolved substantially to include (i) the actions of signaling molecules that are not classically viewed as CV signaling molecules, some of which exert effects at CNS targets in a non-traditional manner, and (ii) CNS locations not traditionally viewed as central autonomic cardiovascular centers. This review summarizes recent work implicating immune signals and reproductive hormones, as well as gasotransmitters and reactive oxygen species in the pathogenesis of hypertension at traditional CV control centers. Additionally, recent work implicating non-conventional CNS structures in CV regulation is discussed.


Nuclear localization of the p75 neurotrophin receptor intracellular domain.
The p75 neurotrophin receptor, a member of the tumor necrosis factor superfamily of receptors, undergoes an alpha-secretase-mediated release of its extracellular domain, followed by a gamma-secretase-mediated intramembrane cleavage. Like amyloid precursor protein and Notch, gamma-secretase cleavage of the p75 receptor releases an intracellular domain (ICD). However, it has been experimentally challenging to determine the precise subcellular localization and functional consequences of the p75 ICD. Here, we utilized a nuclear translocation assay and biochemical fractionation approaches to follow the fate of the ICD. We found that the p75 ICD can translocate to the nucleus to activate a green fluorescent protein reporter gene. Furthermore, the p75 ICD was localized in nuclear fractions. Chromatin immunoprecipitation experiments indicated that nerve growth factor induced the association of endogenous p75 with the cyclin E(1) promoter. Expression of the p75 ICD resulted in modulation of gene expression from this locus. These results suggest that the p75 ICD generated by gamma-secretase cleavage is capable of modulating transcriptional events in the nucleus.


Healthcare-associated risk factors of vancomycin-resistant Enterococci colonization among outpatients undergoing hemodialysis.
Stool specimens and data were obtained from 399 outpatients undergoing hemodialysis (HD) in order to estimate the colonization rate of vancomycin-resistant enterococci (VRE) and to determine risk factors for VRE acquisition. The prevalence of VRE colonization in outpatients ranged from 0%-22.2%. Risk factors associated with VRE colonization were high hierarchy of hospital, short duration of HD, recent hospitalization, prior use of antimicrobial products, high platelet count, and low hemoglobin/albumin/blood urea nitrogen/creatinine levels, showing that VRE colonization was more common in patients with prior infections and poor nutritional status. Although pulsed-field gel electrophoresis (PFGE) analysis showed that most VRE isolates had diverse patterns, 2 paired cases from separate hospitals presented identical PFGE types.


The synaptic physiology of cochlear hair cells.
Mechanosensory hair cells of the vertebrate inner ear are so-called 'short' receptors that communicate to the central nervous system by way of chemical synapses with afferent neurons. In turn, hair cells are the targets of olivocochlear fibers that carry efferent inhibitory feedback from the brain. These synaptic activities contribute to, or modulate the hair cell's receptor potentials through the gating of associated ion channels. Thus for example, voltage-gated calcium channels open to trigger vesicle fusion and release of transmitter by entry of extracellular calcium. The inward calcium current also depolarizes the membrane and could lead to generation of 'all-or-none' action potentials. However, regenerative depolarization is prevented in most hair cells by prominent voltage-gated potassium conductances that rapidly repolarize the membrane. The magnitude and speed of these delayed potassium conductances determine the size and shape of the resulting receptor potential, and subsequent transmitter release, produced by sound. Efferent feedback is provided by the release of acetylcholine (ACh) from olivocochlear nerve fibers onto outer hair cells in the mammalian cochlea. The hair cell's ACh receptors are ligand-gated cation channels related to the nicotinic receptors of nerve and muscle. Calcium influx through the ACh receptors activates nearby calcium-gated potassium channels, resulting in hyperpolarization and inhibition of the hair cell. Calcium influx during efferent inhibition is regulated by a 'synaptic cistern' that also may act as a calcium store that is triggered by ACh under some conditions.


The Nutritional Content of Rescued Food Conveyed by a Food Aid Organization.
The number of food-insecure families in the European Union has increased, resulting in an increasing number of households depending on food assistance programs. The aim in this study was to evaluate the nutrient content of food rescued by a food aid organization that rescues and redistributes fresh or freshly cooked food to low-income households. To determine the nutritional content of food hampers provided by our case study organization, we weighed all items of food hampers in three weighing rounds over a period of four months. The Food Insecurity Experience Scale (FIES) was applied to measure households' food insecurity. Our results show that, at our case study food aid organization, food donations substantially contribute to energy, macro, and micronutrient dietary recommendation intake (DRI). When evaluating how these nutrients contribute to alleviating food insecurity of the beneficiary households, we found that the perception of food insecurity is independent of the amount of nutrients served. To the best of our knowledge, this is the first study measuring the nutritional content of fresh or freshly cooked rescued food conveyed by a food aid organization.


Inhibition of cytolytic lymphocytes by homologous restriction factor. Lack of species restriction.
Homologous restriction factor (HRF) has been shown to inhibit complement-mediated lysis in a species-restrictive manner. Human HRF is able to block lysis by human complement but not by complement from other species. HRF has also been found in the membrane of lymphokine-activated killer (LAK) cells. When this HRF is inserted into sheep erythrocyte membranes, it is able to protect the erythrocyte from LAK cell lysis. In this report, we show that while HRF can inhibit human complement but not rat complement-mediated hemolysis, it is able to inhibit LAK cell lysis by both human and rat LAK cells. HRF is therefore a more general protective protein than has been previously thought.


Layer-controlled evolution of electron state in the silicene intercalation compound SrSi2.
Silicene, a Si-based analogue of graphene, holds a high promise for electronics because of its exceptional properties but a high chemical reactivity makes it a very challenging material to work with. The silicene lattice can be stabilized by active metals to form stoichiometric compounds MSi2. Being candidate topological semimetals, these materials provide an opportunity to probe layer dependence of unconventional electronic structures. It is demonstrated here that in the silicene compound SrSi2, the number of monolayers controls the electronic state. A series of films ranging from bulk-like multilayers down to a single monolayer have been synthesized on silicon and characterized with a combination of techniques - from electron and X-ray diffraction to high-resolution electron microscopy. Transport measurements reveal evolution of the chiral anomaly in bulk SrSi2 to weak localization in ultrathin films down to 3 monolayers followed by 3D and 2D strong localization in 2 and 1 monolayers, respectively. The results outline the range of stability of the chiral state, important for practical applications, and shed light on the localization phenomena in the limit of a few monolayers.


Disadvantaged Parents' Engagement with a National Secondhand Smoke in the Home Mass Media Campaign: A Qualitative Study.
Mass media campaigns can be effective in tobacco control but may widen health inequalities if they fail to engage disadvantaged smokers. This qualitative study explored how parents with young children living in disadvantaged circumstances engaged with a national campaign which aimed to raise awareness of the importance of smokefree homes. Individual semi-structured interviews were carried out with 17 parents before and after the Scottish 2014 "Right Outside" mass media campaign. A conceptual framework exploring meaningful exposure (recall and understanding), motivational responses (protecting children from secondhand smoke (SHS)) and opportunities to act (barriers) was used to thematically analyse the findings. Campaign recall and engagement, and motivation to protect children were high. Parents identified with the dramatized scenario and visual impact of SHS harm to children in the TV advertisement. Some reported changed smoking practices. However, supervising young children in limited accommodation when caring alone constrained opportunities to smoke outside. Instead, parents described actions other than smoking outside that they had taken or were planning to take to create smokefree homes. Mass media campaigns using emotive, real-life circumstances can be effective in engaging parents about SHS. However, the behavioural impact may be limited because of difficult home environments and circumstances.


cis-2,2'-Bipyrimidine-bridged polynuclear complex: a stairway-like mixed-valent {Fe(4)} cluster.
We report the first example of a polynuclear discrete coordination compound exhibiting only bpym bridges and containing a first-row d transition metal. A smooth self-assembly one-pot synthetic route, starting from simply FeCl(2) and FeCl(3) hydrates, allowed us to prepare a tetranuclear Fe(4) cluster with a stairway-like structure and the formula cis-{[(H(2)O)Cl(3)Fe(III)-μ(bpym)Fe(II)Cl(2)]}(2)-μ(bpym) (1) . All spectroscopic data suggest that complex 1 is a valence-localized mixed-valent Fe(II)-Fe(III) cluster with typical Mössbauer lines for both sites, which do not change with temperature. Reflectance spectroscopy did not allow one to distinguish an intervalence charge-transfer band. However, time-dependent density functional theory (DFT) calculations predict a weak high-energy Fe(II) → Fe(III) transition. Regarding the magnetic properties, the high-spin Fe(II) and Fe(III) ions interact in a weakly antiferromagnetic way with isotropic J constants of only a few wavenumbers as derived from direct-current susceptibility and magnetization data. Broken-symmetry DFT calculations support these observations.


Neuronal responses in extrastriate cortex to objects in optic flow fields.
During locomotion, observers respond to objects in the environment that may represent obstacles to avoid or landmarks for navigation. Although much is known about how visual cortical neurons respond to stimulus objects moving against a blank background, nothing is known about their responses when objects are embedded in optic flow fields (the patterns of motion seen during locomotion). We recorded from cells in the lateral suprasylvian visual area (LS) of the cat, an area probably analogous to area MT. In our first experiments, optic flow simulations mimicked the view of a cat trotting across a plain covered with small balls; a black bar lying on the balls served as a target object. In subsequent experiments, optic flow simulations were composed of natural elements, with target objects representing bushes, rocks, and variants of these. Cells did not respond to the target bar in the presence of optic flow backgrounds, although they did respond to it in the absence of a background. However, 273/423 cells responded to at least one of the taller, naturalistic objects embedded in optic flow simulations. These responses might represent a form of image segmentation, in that cells detected objects against a complex background. Surprisingly, the responsiveness of cells to objects in optic flow fields was not correlated with preferred direction as measured with a moving bar or whole-field texture. Because the direction of object motion was determined solely by receptive-field location, it often differed considerably from a cell's preferred direction. About a quarter of the cells responded well to objects in optic flow movies but more weakly or not at all to bars moving in the same direction as the object, suggesting that the optic flow background modified or suppressed direction selectivity.


The effect of lithium on the renal response to the dopamine prodrug gludopa in normal man.
1. The effect of oral lithium on the renal response to gamma-L-glutamyl-L-dopa (gludopa, 25 micrograms kg-1 min-1) was investigated in seven normal males. 2. Gludopa at this dose produced an 800-fold increase in urine dopamine excretion. It was natriuretic and suppressed plasma renin activity without altering blood pressure and pulse. 3. Lithium alone increased sodium excretion and stimulated plasma renin activity. However, it abolished the natriuresis produced by gludopa. 4. Gludopa did not significantly affect lithium clearance. 5. This study suggests that lithium interacts with dopamine at the proximal tubule and that the lithium clearance method is not suitable for investigating dopaminergic mechanisms in the kidney.


The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma.
The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous beta-catenin, gamma-catenin, p120-catenin, and E-cadherin, as well as nuclear beta-catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of beta-catenin was inversely related to distant metastases.


Adding Alzheimer's. The industry targets a growing market.
The gaga, go-go early boom may be over for assisted living, but life most definitely goes on for owners and operators. True, money isn't as easy to come by as it once was, as Wall Street analysts and financiers worry about overbuilding and the quality of earnings. The competition is getting more intense and savvier daily. Fill-up time has lengthened, especially in secondary markets where barriers to entry are low. Most of the affluent suburbs that showed up in everybody's initial feasibility studies are now saturated with high-end assisted living facilities. And the capital crunch has turned many cash-strapped developers into eager sellers. But consumer demand keeps growing, and the demographics look even brighter 10 or 20 years down the line. The trick is to find new ways to distinguish yourself from your competition--and, perhaps, to attract financing. In this year's special section, we suggest several ways of accomplishing both of those goals.


[The hospital medical director: his role and professional qualification in Modena (Italy) health care system].
The development of health care system in Italy, from 1968, have changed the hospital medical director function and have put him in conflict with the desired physicians involvement in health care management. In Modena the health care system organisation, the self government and the responsibility decentralisation, promoted the achievement of an organisation model tempering every competence because the success of everyone's task depends on the other one's. Therefore, Italian laws are suitable of getting more efficiency and effectiveness in health care system without new rules, if the clinical governance becomes a way to involve the physicians in management and not an instrument to leave out managers and hospital medical directors.


Apparent Greig cephalopolysyndactyly and sinus node disease.
We present the clinical findings and follow-up data from birth to 10.5 years in a boy with Greig cephalopolysyndactyly who, in addition, presents sinus node disease ("sick sinus syndrome"). The significance of the concurrence of Greig cephalopolysyndactyly syndrome, an autosomal dominant condition mapped at 7p13, and sinus node disease is discussed.


Blueberries reduce pro-inflammatory cytokine TNF-α and IL-6 production in mouse macrophages by inhibiting NF-κB activation and the MAPK pathway.
Blueberries (BB) have been reported to attenuate atherosclerosis in apoE-deficient (ApoE(-/-) ) mice. The aim of this study was to evaluate the effects of BB in reducing pro-inflammatory cytokine production in mouse macrophages. ApoE(-/-) mice were fed AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried BB for 5 wk. TNF-α and IL-6 were lower in serum of BB-fed mice and TNF-α expression in aorta was down-regulated with BB feeding. Protein level and mRNA expression of TNF-α and IL-6 were significantly lower in the peritoneal macrophages from mice fed BB without or with LPS or oxLDL stimulation. RAW264.7 macrophages were treated with polyphenol-enriched extracts made from the sera of rats fed CD (SEC) or CD containing 10% BB (SEB). SEB significantly inhibited LPS-induced mRNA expression and protein levels of TNF-α and IL-6. Furthermore, SEB inhibited the phosphorylation of IκB, NF-κB p65, MAPK p38 and JNK. All of these are important signaling pathways involved in the production of TNF-α and IL-6.


Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis.
Experiments have demonstrated interlobe differences in the incidence of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCCA), with a 100% incidence in the left and right median lobes and a 30% incidence in the right anterior lobe 20 weeks after exposure began. These tumor data provide a model to test the hypothesis that chemically induced neoplasia can be qualitatively and quantitatively related to promutagenic DNA damage and concurrent cell replication. Experiments were performed to measure O4-ethyldeoxythymidine (O4-EtdT) (a major pro-mutagenic lesion in hepatic DNA of rats exposed to DEN), N7-ethylguanine, cell replication and hepatocyte initiation using the induction of growth-selected gamma-glutamyl transferase-positive (GGT+) foci in the left and right median and right anterior hepatic lobes following 0, 3, 7, 14 or 28 days of DEN administration. Results demonstrated that O4-EtdT concentrations were consistently higher in the left and right median versus the right anterior hepatic lobes, while cell replication was transiently higher in the right median and right anterior lobes. Likewise, high numbers of GGT+ foci were observed in the left and right median lobes in DEN-exposed rats subjected to a Cayama-Farber growth selection protocol. Following administration of [14C]DEN, the distribution of radioactivity showed a marked left lobe preference in 4-week-old rats that had no prior exposure to DEN and in 8-week-old rats exposed to DEN for 4 weeks. This study suggests that interlobe differences in hepatocyte initiation and the incidence of HCCA may be due in part to differences in cell replication and in DNA alkylation resulting from differential DEN distribution and/or metabolism.


Springing into Action: Reg2 Negatively Regulates Snf1 Protein Kinase and Facilitates Recovery from Prolonged Glucose Starvation in Saccharomyces cerevisiae.
Glucose is the preferred carbon source for the yeast Saccharomyces cerevisiae Glucose limitation activates Snf1 protein kinase, a key regulator of energy homeostasis that promotes utilization of alternative carbon sources and enforces energy conservation. Snf1 activation requires phosphorylation of its T-loop threonine (Thr210) by upstream kinases. When glucose is abundant, Snf1 is inhibited by Thr210 dephosphorylation. This involves the function of the type 1 protein phosphatase Glc7, which is targeted to Snf1 by a regulatory subunit, Reg1. The reg1 mutation causes increased Snf1 activity and mimics various aspects of glucose limitation, including slower growth. Reg2 is another Glc7 regulatory subunit encoded by a paralogous gene, REG2 Previous evidence indicated that the reg2 mutation exacerbates the Snf1-dependent slow-growth phenotype caused by reg1, suggesting a link between Reg2 and Snf1. Here, we explore this link in more detail and present evidence that Reg2 contributes to Snf1 Thr210 dephosphorylation. Consistent with this role, Reg2 interacts with wild-type Snf1 but not with nonphosphorylatable Snf1-T210A. Reg2 accumulation increases in a Snf1-dependent manner during prolonged glucose deprivation, and glucose-starved cells lacking Reg2 exhibit delayed Snf1 Thr210 dephosphorylation and slower growth recovery upon glucose replenishment. Accordingly, cells lacking Reg2 are outcompeted by wild-type cells in the course of several glucose starvation/replenishment cycles. Collectively, our results support a model in which Reg2-Glc7 contributes to the negative control of Snf1 in response to glucose refeeding after prolonged starvation. The competitive growth advantage provided by Reg2 underscores the evolutionary significance of this paralog for S. cerevisiae The ability of microorganisms to respond to stress is essential for their survival. However, rapid recovery from stress could be equally crucial in competitive environments. Therefore, a wise stress response program should prepare cells for quick recovery upon reexposure to favorable conditions. Glucose is the preferred carbon source for the yeast S. cerevisiae Glucose depletion activates the stress response protein kinase Snf1, which functions to limit energy-consuming processes, such as growth. We show that prolonged glucose deprivation also leads to Snf1-dependent accumulation of Reg2 and that this protein helps to inhibit Snf1 and to accelerate growth recovery upon glucose replenishment. Cells lacking Reg2 are readily outcompeted by wild-type cells during glucose depletion/replenishment cycles. Thus, while prolonged glucose deprivation might seem to put yeast cells "on their knees," concomitant accumulation of Reg2 helps configure the cells into a "sprinter's crouch start position" to spring into action once glucose becomes available.


Artificial Peroxidase/Oxidase Multiple Enzyme System Based on Supramolecular Hydrogel and Its Application as a Biocatalyst for Cascade Reactions.
Inspired by delicate structures and multiple functions of natural multiple enzyme architectures such as peroxisomes, we constructed an artificial multiple enzyme system by coencapsulation of glucose oxidases (GOx) and artificial peroxidases in a supramolecular hydrogel. The artificial peroxidase was a functional complex micelle, which was prepared by the self-assembly of diblock copolymer and hemin. Compared with catalase or horseradish peroxidase (HRP), the functional micelle exhibited comparable activity and better stability, which provided more advantages in constructing a multienzyme with a proper oxidase. The hydrogel containing the two catalytic centers was further used as a catalyst for green oxidation of glucose, which was a typical cascade reaction. Glucose was oxidized by oxygen (O2) via the GOx-mediated reaction, producing toxic intermediate hydrogen peroxide (H2O2). The produced H2O2 further oxidized peroxidase substrates catalyzed by hemin-micelles. By regulating the diffusion modes of the enzymes and substrates, the artificial multienzyme based on hydrogel could successfully activate the cascade reaction, which the soluble enzyme mixture could not achieve. The hydrogel, just like a protective covering, protected oxidases and micelles from inactivation via toxic intermediates and environmental changes. The artificial multienzyme could efficiently achieve the oxidation task along with effectively eliminating the toxic intermediates. In this way, this system possesses great potentials for glucose detection and green oxidation of a series of substrates related to biological processes.


The nonoxidative conversion of nitroethane to ethylnitronate in Neurospora crassa 2-nitropropane dioxygenase is catalyzed by histidine 196.
The deprotonation of nitroethane catalyzed by Neurospora crassa 2-nitropropane dioxygenase was investigated by measuring the formation and release of ethylnitronate formed in turnover as a function of pH and through mutagenesis studies. Progress curves for the enzymatic reaction obtained by following the increase in absorbance at 228 nm over time were visibly nonlinear, requiring a logarithmic approximation of the initial reaction rates for the determination of the kinetic parameters of the enzyme. The pH dependence of the second-order rate constant k cat/ K m with nitroethane as substrate implicates the presence of a group with a p K a of 8.1 +/- 0.1 that must be unprotonated for nitronate formation. Mutagenesis studies suggest that this group is histidine 196 as evident from the inability of a H196N variant form of the enzyme to catalyze the formation of ethylnitronate from nitroethane. Replacement of histidine 196 with asparagine resulted in an approximately 15-fold increase in the k cat/ K m with ethylnitronate as compared to the wild-type, which results from the inability of the mutant enzyme to undergo nonoxidative turnover. The results presented herein are consistent with a branched catalytic mechanism for the enzyme in which the ethylnitronate intermediate formed from the H196-catalyzed deprotonation of nitroethane partitions between release from the active site and oxidative denitrification to yield acetaldehyde and nitrite.


Papillomavirus DNA complementation in vivo.
Recent phylogenic studies indicate that DNA recombination could have occurred in ancient papillomavirus types. However, no experimental data are available to demonstrate this event because of the lack of human papillomavirus infection models. We have used the cottontail rabbit papillomavirus (CRPV)/rabbit model to study pathogenesis and immunogenicity of different mutant genomes in vivo. Although the domestic rabbit is not a natural host for CRPV infection, it is possible to initiate infection with naked CRPV DNA cloned into a plasmid and monitor papilloma outgrowth on these animals. Taking advantage of a large panel of mutants based on a CRPV strain (Hershey CRPV), we tested the hypothesis that two non-viable mutant genomes could induce papillomas by either recombination or complementation. We found that co-infection with a dysfunctional mutant with an E2 transactivation domain mutation and another mutant with an E7 ATG knock out generated papillomas in rabbits. DNA extracted from these papillomas contained genotypes from both parental genomes. Three additional pairs of dysfunctional mutants also showed similar results. Individual wild type genes were also shown to rescue the function of corresponding dysfunctional mutants. Therefore, we suggest that complementation occurred between these two non-viable mutant PV genomes in vivo.


Smoking and asthma in adults.
Studies on the effect of smoking on adulthood asthma have provided contradictory results. The current authors conducted a population-based incident case-control study to assess the effects of current and past smoking on the development of asthma in adults. During a 2.5 yr study period, all new asthma cases clinically diagnosed (n=521) and randomly selected controls (n=932) from a geographically defined district in southern Finland were recruited. The risk of developing asthma was significantly higher among current smokers with an adjusted odds ratio (OR) of 1.33 (95% confidence interval 1.00-1.77) and among ex-smokers with an adjusted OR 1.49 (1.12-1.97) compared with never-smokers. Among current smokers, the risk increased up to 14 cigarettes x day(-1), and a similar trend was observed in relation to cumulative smoking. In conclusion, the current results support the hypothesis that smoking causes asthma in adulthood.


Management of synkinesis and asymmetry in facial nerve palsy: a review article.
The important sequelae of facial nerve palsy are synkinesis, asymmetry, hypertension and contracture; all of which have psychosocial effects on patients. Synkinesis due to mal regeneration causes involuntary movements during a voluntary movement. Previous studies have advocated treatment using physiotherapy modalities alone or with exercise therapy, but no consensus exists on the optimal approach. Thus, this review summarizes clinical controlled studies in the management of synkinesis and asymmetry in facial nerve palsy. Case-controlled clinical studies of patients at the acute stage of injury were selected for this review article. Data were obtained from English-language databases from 1980 until mid-2013. Among 124 articles initially captured, six randomized controlled trials involving 269 patients were identified with appropriate inclusion criteria. The results of all these studies emphasized the benefit of exercise therapy. Four studies considered electromyogram (EMG) biofeedback to be effective through neuromuscular re-education. Synkinesis and inconsistency of facial muscles could be treated with educational exercise therapy. EMG biofeedback is a suitable tool for this exercise therapy.


Bcl-x(S) anatagonizes the protective effects of Bcl-x(L).
Bcl-x, a member of the Bcl-2 family, has two alternatively spliced forms, Bcl-x(L) and Bcl-x(S). Bcl-x(L), like Bcl-2, is able to protect cells from a wide variety of apoptotic stimuli. Bcl-x(S), as a result of alternative splicing, lacks 63 amino acids that comprise the region of greatest amino acid identity between Bcl-x(L) and Bcl-2. These amino acids contain the highly conserved BH1 and BH2 regions, which have been used to define the Bcl-2 family. We show that both Bel-x(L) and Bcl-x(S) are able to regulate cell survival in a dose-dependent fashion. Bcl-x(L) is able to increase the cellular apoptotic threshold and is able to form stable complexes with Bax both in vitro and in vivo. In contrast, Bcl-x(S) can effectively inhibit the protective effects of Bcl-x(L) following growth factor withdrawal and chemotherapeutic drug treatment. However, compared with Bax, Bcl-x(S) binds to Bcl-x(L) weakly when assessed by in vitro binding assays. Coimmunoprecipitation from mammalian cells demonstrates that Bcl-x(S) does not show an observable ability to form heterodimers with other Bcl-2 family members. In addition, overexpression of Bel-x(S) does not alter the ability of Bax to heterodimerize with Bcl-x(L) in vivo. Thus, Bcl-x(S) does not appear to function by competitively disrupting the formation of dimers composed of other Bcl-2 family members. This suggests that Bcl-x(S) can enhance cellular sensitivity to apoptosis via a mechanism of action distinct from other Bc1-2 family members that promote apoptosis.


Antistaphylococcal penicillins versus cephalosporins for definitive treatment of meticillin-susceptible Staphylococcus aureus bacteraemia: a systematic review and meta-analysis.
The objective of this study was to assess the comparative effectiveness and safety of antistaphylococcal penicillins (ASPs) and cephalosporins for the definitive treatment of patients with meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. PubMed and Scopus electronic databases were searched up to December 2013. All-cause mortality was the primary outcome of interest. A meta-analysis of unadjusted and adjusted data was performed. Seven articles (1643 patients) were included; all but one were retrospective studies, and three of them employed propensity score matching. The studies enrolled primarily adults hospitalised in medical wards for primary or secondary community-acquired, healthcare-associated or nosocomial MSSA bacteraemia. Several ASPs and cephalosporins were compared. Unadjusted 30-day mortality was lower in patients treated with ASPs than in those treated with cephalosporins [risk ratio (RR)=0.62, 95% confidence interval (CI) 0.40-0.98]. Propensity score-adjusted 30-day mortality was not different in patients receiving ASPs or cephalosporins (RR=0.75, 95% CI 0.41-1.39). Substantial heterogeneity and publication bias were found in these analyses. Both unadjusted (RR=0.85, 95% CI 0.54-1.32) and adjusted (RR=1.42, 95% CI 0.22-9.06) 90-day mortality did not differ between patients receiving ASPs or cephalosporins. Limited data regarding adverse events, development of resistance and recurrence were available. In conclusion, the limited available published data derive from retrospective studies and show that there appears to be no statistically significant difference in mortality between ASPs and cephalosporins for the treatment of MSSA bacteraemia.


Potential and limitations of transcranial color-coded sonography in stroke patients.
Transcranial color-coded duplex sonography (TCCS) enables visualization of the intracranial parenchymal structures and measurement of blood flow velocity in the basal cerebral arteries. The present study aims to evaluate prospectively the clinical usefulness of TCCS in patients with acute stroke. Eighty-four consecutive patients with central nervous symptoms suggesting acute stroke were investigated within the first 48 hours after clinical onset. TCCS was performed with a 2.5-MHz sector transducer through the temporal bone window. CT was available in all patients. Forty-eight patients suffered from an infarction or a transient ischemic attack (TIA) in the territory of the middle cerebral artery (MCA). Fifteen of them showed an MCA occlusion, and 12 of the 15 developed recanalization during follow-up. Twelve revealed an increased, decreased, or oscillating flow pattern in the MCA main stem, and 21 patients had no ultrasonic abnormalities. The positive and negative predictive values of a pathological flow pattern in patients with MCA infarctions or TIA were .92 and .48, respectively. Fifteen patients suffered from an intracerebral hematoma, which could be diagnosed by TCCS in 14 cases. The positive and negative predictive values of a pathological parenchymal echo pattern were .88 and .96, respectively. Three patients suffered from an infarction and one from a TIA in the posterior cerebral artery territory. One female patient with an acute deterioration of a hemiparesis showed a glioma. The dropout rate due to an insufficient acoustic temporal bone window was 20% (17/84). TCCS is a noninvasive bedside method that provides rapid and reliable data regarding stroke subtype and mechanism immediately after onset. Window failure is a serious limitation of this method.


The ascending reticular activating system from pontine reticular formation to the thalamus in the human brain.
Action of the ascending reticular activating system (ARAS) on the cerebral cortex is responsible for achievement of consciousness. In this study, we attempted to reconstruct the lower single component of the ARAS from the reticular formation (RF) to the thalamus in the normal human brain using diffusion tensor imaging (DTI). Twenty six normal healthy subjects were recruited for this study. A 1.5-T scanner was used for scanning of diffusion tensor images, and the lower single component of the ARAS was reconstructed using FMRIB software. We utilized two ROIs for reconstruction of the lower single component of the ARAS: the seed ROI - the RF of the pons at the level of the trigeminal nerve entry zone, the target ROI - the intralaminar nuclei of the thalamus at the level of the commissural plane. The reconstructed ARAS originated from the pontine RF, ascended through the mesencephalic tegmentum just posterior to the red nucleus, and then terminated on the intralaminar nuclei of the thalamus. No significant differences in fractional anisotropy, mean diffusivity, and tract number were observed between hemispheres (p > 0.05). We reconstructed the lower single component of the ARAS from the RF to the thalamus in the human brain using DTI. The results of this study might be of value for the diagnosis and prognosis of patients with impaired consciousness.


[Efficacy of WT1 peptide-/MUC-1 peptide-pulsed dendritic cell therapy in 313 patients with a wide range of cancers].
We assessed the efficacy of Wilms' tumor protein-1(WT1)peptide and/or mucin 1(MUC-1)peptide-pulsed dendritic cell(DC)therapy for a wide range of advanced cancers.This retrospective study included 313 patients with advanced cancer who were vaccinated ≥5 times in our clinic between May 2009 and October 2013.T he clinical response was evaluated.This treatment was approved by the ethics panel of our institution.A total of 313 patients were injected an average of 6.0 times with DCs(2.4×10 / 7 cells/injection).Overall, 292 of the 313(93%)patients obtained clinical benefit according to the Response Evaluation Criteria in Solid Tumors(RECIST), version 1.1. The median survival time(MST)from diagnosis and from first being admitted to this institution was 28.4 months and 13.2 months, respectively. Complete response(CR)was achieved in 21 patients(7.2%).Partial response(PR)was achieved in 69 patients(24%).Stable disease(SD)was observed in 107 patients(37%), and progressive disease(PD)was observed in 95 patients(33%).The response rate(RR)and disease control rate(DCR)for each type of cancer were as follows: colorectal cancer(56 patients), 25%and 45%, respectively; lung cancer(39 patients), 31% and 82%, respectively; pancreatic cancer(36 patients), 22% and 64%, respectively; gastric cancer( 34 patients), 32% and 74%; breast cancer(20 patients), 15% and 75%, respectively; ovarian cancer(16 patients), 19% and 50%, respectively; esophageal cancer(15 patients), 20% and 73%, respectively; and others(76 patients), 38% and 67%.These results demonstrated the potential clinical effectiveness of DC-based immunotherapy.


EEG Correlates of Ten Positive Emotions.
Compared with the well documented neurophysiological findings on negative emotions, much less is known about positive emotions. In the present study, we explored the EEG correlates of ten different positive emotions (joy, gratitude, serenity, interest, hope, pride, amusement, inspiration, awe, and love). A group of 20 participants were invited to watch 30 short film clips with their EEGs simultaneously recorded. Distinct topographical patterns for different positive emotions were found for the correlation coefficients between the subjective ratings on the ten positive emotions per film clip and the corresponding EEG spectral powers in different frequency bands. Based on the similarities of the participants' ratings on the ten positive emotions, these emotions were further clustered into three representative clusters, as 'encouragement' for awe, gratitude, hope, inspiration, pride, 'playfulness' for amusement, joy, interest, and 'harmony' for love, serenity. Using the EEG spectral powers as features, both the binary classification on the higher and lower ratings on these positive emotions and the binary classification between the three positive emotion clusters, achieved accuracies of approximately 80% and above. To our knowledge, our study provides the first piece of evidence on the EEG correlates of different positive emotions.


A new growth inhibitor, pisumin, involved in light inhibition of epicotyl growth of dwarf peas.
A new growth inhibitor, tentatively named pisumin, which increased under red light and remained at initial level or decreased when dwarf pea (Pisum sativum L. cv Progress No. 9) seedlings were transferred from red light to dark, has been isolated in the form of a colorless powder from light-exposed epicotyls of dwarf peas, and characterized partially as an aliphatic carboxylic acid (molecular weight 284) by spectrometric analyses.Exogenous pisumin inhibited the growth of epicotyl segments of dwarf peas at concentrations higher than 0.1 millimolar in the dark.


Objective method to evaluate the competency of residents in cardiac surgery.
Cardiac surgery training has become more challenging as patients and their diagnoses become more complex. Our goal was to develop a multicategorical assessment model for evaluating residents in cardiac surgery. This model is intended to ensure goal-directed progress in their training as well as to recognize and support their surgical talents. We developed a new questionnaire in a multistage, 3-round process based on the Delphi method 'estimate-talk-estimate', using 55 competencies, including 38 general and 17 domain-specific competencies. Each competency is evaluated with 1 or more questions, to which 1 (not competent) to 6 (very competent) points can be chosen as an answer. The resulting model achieved 2 main goals: first, presenting a well-defined competency list for cardiac surgical training and second, providing an objective and realistic evaluation of trainees' abilities. Residents were assessed by all trainers to achieve a high level of objectivity. This evaluation model is highly objective, because residents are evaluated by multiple trainers. It allows individual support and enables better transparency in residency training. Talents and skills are evaluated, recognized and adopted as a base for individual feedback and personalized training programmes.


A novel role of alkaline phosphatase in protection from immunological liver injury in mice.
Little is known about the role of alkaline phosphatase (AP) in liver diseases, except for its elevation in jaundice or cholestasis. Its substrate, endotoxin, is usually elevated in patients as well as animals with liver damage. This study aimed to provide evidence for its new role as protection against immunological liver damage. Liver injury was induced in mice by delayed-type hypersensitivity to picryl chloride. AP activity was measured using a commercial kit. In acute liver injury, a significant decrease in AP activity in serum was observed but there was an increase in liver tissue. Single administration of cyclophosphamide before sensitization with picryl chloride exacerbated the liver injury, with more serious AP changes, while consecutive use after the sensitization alleviated the injury with a recovery from the changes. When liver injury proceeded for 1 week, both serum and liver showed decreased AP activity. Lipopolysaccharide facilitated alanine transaminase release from levamisole-pretreated but not non-treated hepatocytes from naive mice. However, the release was confirmed from liver slices of mice with liver injury proceeding for 1 week, even without levamisole pretreatment. The development of liver injury may lead to a dysfunction in AP synthesis and release. Levamisole may make normal hepatocytes, like the hepatocytes from liver-injured mice, highly sensitive to lipopolysaccharide through inhibiting AP synthesis. The findings obtained in this study suggest that AP may contribute to protection from injury by a mechanism involving neutralization of endotoxin.


Home alone: assessing mobility independence before discharge.
Hospitalists are often confronted with discharge planning responsibility and decisions for elderly patients who live alone. The absence of an in-home helper (spouse, partner, or care-giver) reduces the margin of safety and resilience to any new debility. Research has documented that during hospital stays elderly patients tend to become deconditioned, even if there is no new specific neurologic or motor deficit. In the patient whose pre-hospital mobility independence is not robust, and perhaps marginally compensated, inpatient stays for any diagnosis may result in critical decrements in mobility independence. The present study is an effort to design a bedside tool for the hospitalist by which to discern, or screen, for such debility. The tool is a hierarchical performance test we named I-MOVE (Independent Mobility Validation Examination). It is a quick series of bedside mobility requests to demonstrate capability of fundamental movements critical to independent living. We describe manner in which I-MOVE can be performed. Moreover, we describe the face validity and the high interrater reliability (> 0.90 intra-class correlation coefficient) of two RNs who independently administered and scored I-MOVE for 41 patients on a General Medical Care Unit. Although not yet studied in correlation with outcomes, nor with validated mobility assessment tools, we believe I-MOVE can serve as a useful extension of the nurse's assessment, or the Hospitalist's physical examination. Discerning the continued capability of mobility independence is a desirable, on-going insight for discharge planning of the elderly patient who resides alone.


Management of adolescent and adult inpatients with cystic fibrosis.
A program in which pharmacists help care for cystic fibrosis patients is described. The Egleston Cystic Fibrosis Center at Emory University houses outpatient clinic facilities and a 10-bed inpatient unit and is affiliated with Egleston Children's Hospital. The center provides full-service care for nearly 500 patients. Patients with mild to moderate exacerbations of pulmonary problems can receive their entire course of therapy at the center, and those with severe illness may complete their hospital stay there. A care team consisting of pharmacists, physicians, nurses, and others provides preventive and acute care. Patients can choose a "care partner" who will assist them with their care during any hospitalizations and at home. Both patient and care partner are taught drug administration, nutrition, and physical therapy and meet regularly with the care team. Patients must receive their medication education from a pharmacist before they can administer their own drugs. Pharmacists at the center also evaluate serum drug concentrations, stock the automated dispensing device, monitor for drug interactions, answer drug information questions, and attend multidisciplinary rounds. Pharmacy residents can work with the care team through rotations and clinic experience. Pharmacists at a cystic fibrosis center provide clinical services to patients and promote self-care.


Recognising the potential of large animals for modelling neuromuscular junction physiology and disease.
The aetiology and pathophysiology of many diseases of the motor unit remain poorly understood and the role of the neuromuscular junction (NMJ) in this group of disorders is particularly overlooked, especially in humans, when these diseases are comparatively rare. However, elucidating the development, function and degeneration of the NMJ is essential to uncover its contribution to neuromuscular disorders, and to explore potential therapeutic avenues to treat these devastating diseases. Until now, an understanding of the role of the NMJ in disease pathogenesis has been hindered by inherent differences between rodent and human NMJs: stark contrasts in body size and corresponding differences in associated axon length underpin some of the translational issues in animal models of neuromuscular disease. Comparative studies in large mammalian models, including examination of naturally occurring, highly prevalent animal diseases and evaluation of their treatment, might provide more relevant insights into the pathogenesis and therapy of equivalent human diseases. This review argues that large animal models offer great potential to enhance our understanding of the neuromuscular system in health and disease, and in particular, when dealing with diseases for which nerve length dependency might underly the pathogenesis.


A critical review of the 10 pivotal caries clinical studies used in a recent meta-analysis comparing the anticaries efficacy of sodium fluoride and sodium monofluorophosphate dentifrices.
The 10 pivotal caries clinical studies employed in a recent meta-analysis to compare the anticaries efficacy of sodium fluoride (NaF) and sodium monofluorophosphate (MFP) dentifrices were subjected to a critical review. When reporting the meta-analysis, the author (Johnson) considered these 10 pivotal caries clinical studies as "head-to-head" comparisons of NaF and MFP dentifrices. For the most part, it is difficult to find any common denominator among these 10 caries clinical studies since there were so many diverse factors associated with them. The 10 pivotal studies were conducted over a 20-year period of time in many different geographic areas of the world, using different protocols and study designs, different clinical examiners and caries assessment criteria, as well as evaluating commercially outdated or specially formulated dentifrices. Any attempt to integrate the results from these 10 studies is further complicated by the diversity of statistical methodology used to evaluate the results obtained from the studies. Also, in two of the 10 studies, the comparison of the fluoride dentifrices was obscured by the fact that the participating children used a fluoride mouthrinse during the course of the study. In any case, when all relevant dentifrice comparisons are made, the results of a critical review of the 10 pivotal ("head-to-head") caries clinical studies indicate the following: (1) In three of the studies (Gerdin/Zacherl/Forsman), depending upon how the data is viewed, it can either be shown that NaF dentifrices are favored over MFP dentifrices or that MFP dentifrices are favored over NaF dentifrices. (2) In one of the studies (Edward & Torell), the results are published only in abstract form and a full report of the study is not available. (3) In one of the studies (Koch, Petersson, Kling & Kling) it is reported that MFP dentifrices are favored over NaF dentifrices. (4) In two of the studies (Edlund & Koch, Koch et al) it is reported that NaF dentifrices are favored over MFP dentifrices. However, in both of these studies, there were serious imbalances in baseline caries status favoring the NaF dentifrice groups over the MFP dentifrice groups. In other words, the children using the MFP dentifrices were more prone to caries formation during the course of these studies than the children using the NaF dentifrices. Further, in these two studies there is a serious question regarding the soluble fluoride level of the commercially available MFP dentifrice that was used.(ABSTRACT TRUNCATED AT 400 WORDS)


Spatiotemporal distribution of pollutants and impact of local meteorology on source influence on pollutants' level in a traffic air-shed in Lagos megacity, Nigeria.
Pollution from vehicular emissions is a major cause of poor air quality observed in many urban and semi-urban towns and cities. As such, this study was conducted to assess air quality and the spatiotemporal distribution of vehicular and traffic-related pollutants in several air sheds of Lagos megacity, the economic nerve centre of Nigeria. A setup of low-cost air quality sensors comprising five (5) units was deployed between November 2018 and February 2019 within traffic corridors in the heart of the city. Diurnal variation of pollutants indicated that carbon dioxide (CO2) peaked during the early hours of the day, total oxide (Ox = NO2+O3) peaked at mid-day while carbon monoxide (CO) had two distinct peaks which correspond to morning and evening rush hours. Nitrogen dioxide (NO2) concentration peaked during evening hours. Average concentrations are NO2 (97.1 ± 9.7) ppb, Ox (78.6 ± 27.2) ppb, CO2 (450.1 ± 31.2) ppm, and CO (2285.63 ± 743.7) ppb. Average concentrations of pollutants were above thresholds set by the World Health Organization (WHO) except for NO2 which was within the range permissible limits. The implication of this is that the atmosphere is polluted due to elevated concentrations of airborne pollutants, an indication which is of both health and environmental concern. The air quality index (AQI) indicates that the quality of ambient air varies from good to very unhealthy for Ox, and unhealthy to very unhealthy for CO, while AQI for PM2.5 and PM10 showed hazardous at all the sampling locations except at UNILAG where it is unhealthy for the sensitive group. For all of the sampling sites, conditional bivariate probability function (CBPF) plots show a significant agreement with the location of known pollution sources.


Surgical indications in low lumbar burst fractures: experiences with Anterior Locking Plate System and the reduction-fixation system.
A study of 14 surgically treated patients with low lumbar burst fractures (L3 to L5) is reported. Initially, 13 patients presented with incomplete neurologic deficits below the level of injury. The follow-up period ranged from 24 to 40 months, with an average of 30 months. In group 1, seven patients underwent one-stage anterior decompression, fusion, and Anterior Locking Plate System (ALPS) fixation. In Group 2, seven patients had posterior surgery with decompression, portero-lateral fusion, and a short segment fixation, one above and one below the injuried level, with the reduction-fixation transpediculate system. Indications for one-stage anterior surgery consisted of patients with incomplete neurologic deficits, segmental kyphotic deformity caused by loss of anterior vertebral height (< 50%), or canal encroachment < 50%. When there is significant radiologic evidence of lamina fractures, displaced or greenstick type, or injuries that occurred at the L5 level, the posterior approach was undertaken initially. This may be followed by anterior surgery if satisfactory vertebral height restoration or canal clearance was not achieved. Five dura tears (36%) were noted during surgery: two tears in group 1 and three tears in group 2. There were two patients in group 2 (29%) who had screws broken; however, none in group 1 demonstrated implant failure. In the low lumbar region, the step-off ALPS plate is preferable to the straight plate because of the increasing size of the vertebral body toward the caudal area. A low profile and easy application were its advantages. However, the ALPS could not be distracted or compressed anteriorly.


Surgical volume and outcomes of off-pump coronary artery bypass graft surgery: Does it matter?
Coronary artery bypass grafting performed off-pump has emerged in recent years as a less morbid alternative to on-pump bypass grafting. However, the impact of hospital volume on the outcomes of off-pump relative to on-pump bypass grafting has not been evaluated. We conducted a retrospective study of patients undergoing off-pump (n = 26,011) and on-pump (n = 99,344) coronary artery bypass grafting during 2000 through 2004 in 124 California hospitals, using the California Patient Discharge Database. Generalized linear mixed models were used to compare in-hospital mortality and postoperative complications in patients undergoing on-pump versus off-pump bypass grafting, accounting sequentially for differences in patient characteristics and hospital-level effects. The relative mortality and complication rates for patients undergoing on-pump versus off-pump coronary bypass were evaluated across hospital volume quartiles. Mean length of stay was lower for patients who underwent off-pump compared with on-pump bypass grafting (8.7 vs 9.6 days; P < .001), as were unadjusted mortality and complication rates (2.2% vs 3.3%; 10.1% vs 11.6%, respectively; P < .001). For hospitals in the highest percent off-pump bypass quartile, adjusted mortality and complication rates for patients having off-pump bypass were significantly lower than for the on-pump group (odds ratio [OR] = 0.50; 95% confidence intervals [CI], 0.41-0.61; OR = 0.73; 95% CI, 0.66-0.81, respectively; P < .001); by contrast, for hospitals in the lowest percent off-pump bypass quartile, mortality and complications were similar in off-pump and on-pump groups (OR = 1.10; 95% CI, 0.75-1.63; OR = 0.92; 95% CI, 0.72-1.16, respectively; P > .05). Outcomes were significantly better for off-pump compared with on-pump coronary artery bypass grafting. Although the benefit of off-pump bypass grafting increased as the relative use of the procedure at a hospital increased, off-pump bypass grafting can be safely implemented across numerous hospitals.


Spontaneous Absorption of Cerebral Air Embolus Developed Accidentally during an Intra-arterial Procedure.
Cerebral arterial air embolism (CAAE), although infrequent, is a complication that can occur at any time during an invasive medical procedure. We experienced two cases of CAAE during cerebral angiography accidentally. The author reports the two cases of CAAE wherein air emboli dissolved spontaneously and immediately under normal atmospheric pressure, not under therapeutic hyperbaric environment. One of the cases shows entire dissolution of the air embolus on the moving image. This report shows that arterial air embolus can be absorbed spontaneously, and air embolus size is one of the factors that influence air embolus dissolution besides hyperbaric oxygen condition.


Gα73B is a downstream effector of JAK/STAT signalling and a regulator of Rho1 in Drosophila haematopoiesis.
JAK/STAT signalling regulates many essential developmental processes including cell proliferation and haematopoiesis, whereas its inappropriate activation is associated with the majority of myeloproliferative neoplasias and numerous cancers. Furthermore, high levels of JAK/STAT pathway signalling have also been associated with enhanced metastatic invasion by cancerous cells. Strikingly, gain-of-function mutations in the single Drosophila JAK homologue, Hopscotch, result in haemocyte neoplasia, inappropriate differentiation and the formation of melanised haemocyte-derived 'tumour' masses; phenotypes that are partly orthologous to human gain-of-function JAK2-associated pathologies. Here we show that Gα73B, a novel JAK/STAT pathway target gene, is necessary for JAK/STAT-mediated tumour formation in flies. In addition, although Gα73B does not affect haemocyte differentiation, it does regulate haemocyte morphology and motility under non-pathological conditions. We show that Gα73B is required for constitutive, but not injury-induced, activation of Rho1 and for the localisation of Rho1 into filopodia upon haemocyte activation. Consistent with these results, we also show that Rho1 interacts genetically with JAK/STAT signalling, and that wild-type levels of Rho1 are necessary for tumour formation. Our findings link JAK/STAT transcriptional outputs, Gα73B activity and Rho1-dependent cytoskeletal rearrangements and cell motility, therefore connecting a pathway associated with cancer with a marker indicative of invasiveness. As such, we suggest a mechanism by which JAK/STAT pathway signalling may promote metastasis.


What is the Main Processing Factor Influencing Staphylococcus Species Diversity in Different Manufacturing Units?
The microbiota of traditional dry-cured sausages and industrial environment was assessed to characterize the diversity of coagulase-negative staphylococci (CNS), and establish potential relationships with hygiene level or technological characteristics. Eight processing units from South Portugal were audited according to a checklist of requirements. Environmental and products' samples at different production stages were evaluated regarding hygiene and safety criteria. CNS were recovered, characterized, and their potential use as starters evaluated. Low genetic diversity was observed for Staphylococcus xylosus, whereas Staphylococcus equorum showed diverse genetic profiles. Staphylococcus xylosus predominated in products with a long period of cold smoking, Staphylococcus saprophyticus in products with a long period of hot smoking, Staphylococcus epidermidis in products with a short period of cold smoking, and S. equorum in nonsmoked products. Most S. xylosus were resistant to tetracycline, whereas S. equorum were susceptible. Antibioresistance restricted the selection of starters due to safety recommendations. PRACTICAL APPLICATION: The present manuscript highlighted a few staphylococci strains that could potentially be used as starter cultures in fermented meat products. These selected strains do not show resistance to antimicrobials, exhibit adequate technological features, and are well adapted to the industrial environments of meat processing industries using different processing technologies. Therefore, the selected strains ready to be used in the manufacturing of traditional fermented meat products to ensure safety, standardize product properties, and shorten ripening.


CXCR4 activation promotes differentiation of human embryonic stem cells to neural stem cells.
G protein-coupled receptors (GPCRs) are involved in many fundamental cellular responses such as growth, death, movement, transcription and excitation. Their roles in human stem cell neural specialization are not well understood. In this study, we aimed to identify GPCRs that may play a role in the differentiation of human embryonic stem cells (hESCs) to neural stem cells (NSCs). Using a feeder-free hESC neural differentiation protocol, we found that the expression of several chemokine receptors changed dramatically during the hESC/NSC transition. Especially, the expression of CXCR4 increased approximately 50 folds in NSCs compared to the original hESCs. CXCR4 agonist SDF-1 promoted, whereas the antagonist AMD3100 delayed the neural induction process. In consistence with antagonizing CXCR4, knockdown of CXCR4 in hESCs also blocked the neural induction and cells with reduced CXCR4 were rarely positive for Nestin and Sox1-staining. Taken together, our results suggest that CXCR4 is involved in the neural induction process of hESC and it might be considered as a target to facilitate NSC production from hESCs in regenerative medicine.


Improvements in Quality of Life in Children Following Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in the PEPITES and PEOPLE Studies.
Food allergy quality of life (FAQL) is impaired in children with peanut allergy. Food Allergy Quality of Life Questionnaires (FAQLQs) provide disease-specific insight into the burden of peanut allergy and potential FAQL changes after peanut immunotherapy. To examine FAQL changes in children after treatment with epicutaneous immunotherapy for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg). FAQL was prospectively measured using the FAQLQ parent proxy form (Food Allergy Quality of Life Questionnaire-Parent Proxy Form [FAQLQ-PF], for children aged ≤12 years) and child form (Food Allergy Quality of Life Questionnaire-Child Form [FAQLQ-CF], child rated if aged ≥8 years) during the 12-month double-blind, randomized, controlled Peanut EPIT Efficacy and Safety Study (PEPITES) trial and the initial 12 months of the open-label PEPITES Open Label Extension Study (PEOPLE) follow-up study. Data were analyzed for between-group differences after treatment unblinding. FAQLQs from placebo participants (FAQLQ-PF: 96; FAQLQ-CF: 47) and treatment group participants (FAQLQ-PF: 209; FAQLQ-CF: 105) were analyzed. Twenty-four-month global FAQL scores (FAQLQ-PF/FAQLQ-CF) were significantly improved in the treatment group versus the placebo group (least squares mean, 0.34, P = .008, and 0.46, P = .023, respectively). At 24 months, there was significant FAQLQ-PF score improvement in participants initially randomized to treatment who met the efficacy primary end point (n = 74; least squares mean, 0.55; P < .001) and in participants with any eliciting dose increase (n = 127; least squares mean, 0.66; P < .001). FAQLQ-PF improvements were observed in social dietary limitations (P = .002), food-related anxiety (P = .029), and emotional impact (P = .048) domains. FAQLQ-CF improvements were observed in risk of accidental exposure (P = .002) and allergen avoidance (P = .04) domains. Nearly all outcomes met a nontreatment context minimal clinically important difference previously cited for FAQLQ. Epicutaneous immunotherapy treatment was observed to be associated with significant global and domain-specific FAQL improvement (FAQLQ-PF/FAQLQ-CF), largely driven by increases in eliciting dose, in children with peanut allergy.


Management pitfalls in the use of embolization for the treatment of severe epistaxis.
Angiographic embolization for the treatment of severe recurrent epistaxis was added to the traditional treatment options--nasal packing, cauterization, and surgical vessel ligation--in 1974. Since then, clinical experience has shown that this procedure is safe and effective. When epistaxis cannot be controlled with cautery, nasal packing is the most common next step. As such, it is often performed by emergency physicians and other clinicians who are not otolaryngologists. We report two cases in which intranasal neoplasms were obscured as a result of a significant distortion of the normal anatomy. This distortion was secondary to emergency-room treatment of severe epistaxis by repeated nasal packing followed by angiographic embolization. Pre-embolization angiographic studies and subsequent postembolization endoscopic evaluations did not reveal the presence of the occult neoplasms because of the presence of inflammation and edema after treatment. Clinicians should be aware that nasal packing and embolization can obscure the underlying source of epistaxis, and follow-up radiologic studies and endoscopic evaluations are essential to avoid delays in diagnosis.


Evidence for an influence of the ovary on circulating dehydroepiandrosterone sulfate levels.
Circulating dehydroepiandrosterone sulfate (DS) declines in old age, falling to almost undetectable levels after the seventh decade. Since an accelerated decrease occurs after the menopause, we sought to determine whether ovarian factors may influence adrenal DS secretion independent of chronological age. DS, cortisol, and estradiol levels were compared in subjects grouped according to age, ovarian function, and estrogen replacement. Our data show that premature ovarian failure and ovariectomy in young as well as in postmenopausal subjects precipitate an earlier decline in DS levels. There were no accompanying changes in cortisol levels and no correlations among levels of DS, cortisol, and estradiol. Long term estrogen replacement (over 10 yr) in postmenopausal women over age 65 had no beneficial effect on the age-related DS decline. We suggest that ovarian factors separate from estrogen-mediated effects significantly influence the reduction of DS levels independent of age.


Beta radiation for renal nerve denervation: initial feasibility and safety.
In small clinical trials, sympathetic renal denervation using radiofrequency (RF) energy shows promise in treating resistant hypertension. However, the RF procedure is lengthy and is associated with pain during ablation. Vascular brachytherapy, a proven treatment for in-stent restenosis, has the potential to cause nerve fibrosis. The purpose of the present study was to assess the safety and feasibility of renal artery brachytherapy for sympathetic renal denervation. A total of 10 normotensive domestic swine underwent vascular brachytherapy to left and right renal arteries using the Beta-Cath 3.5 Fr delivery system at doses of 25 Gy (n=8) and 50 Gy (n=8) at 2 mm from the source centre. These groups were compared to untreated arteries that served as control (n=4). Follow-up obtained at one or two months included angiogram, intravascular ultrasound, and histopathology analysis. The vascular brachytherapy procedure was safe and no apparent angiographic or ultrasound injuries to the vessel were seen. Histology showed a varying degree of thermal injury more pronounced in the 50 Gy group. The majority of examined nerves showed some degree of injury; there was a dose-related effect on nerve injury severity. There were varying degrees of arteriolar changes in the examined sections, with most showing a 2-20% degree of endothelial cell loss. This initial feasibility and safety study of renal nerve denervation, mediated by low and intermediate β-radiation dosages, indicates that this approach can cause nerve fibrosis while avoiding significant damage to the renal artery.


Young Adult Perceptions of the British American Tobacco New Zealand Agree/Disagree Plain Packaging Counter-Campaign.
In 2012, British American Tobacco New Zealand (BATNZ) launched a mass media campaign branded "Agree/ Disagree" as a response to the New Zealand government's plans to introduce plain packaging. We examined young adult's views about the campaign to assist tobacco control policymakers in planning future interventions. Interviews with young adults living in the Auckland area were conducted. Interviews covered existing knowledge about plain packaging of tobacco, knowledge about the tobacco industry, and perceptions of specific advertisements included in the campaign. Interview data were analyzed to determine the dominant views about the campaign. Perspectives from 12 interviews reflect the dominant discourse in New Zealand on the benefits of serving economic progress and international trade. Pervasive views about the campaigns reflected perceptions of the risk to the New Zealand image, trade, and economy. Similarly, participants expressed concern about the potential for plain packaging to creep toward other products, such as alcohol. Perceptions of the tobacco industry were mixed but reflect a tolerant view of the ethics of business if viewed to be beneficial to the economy. Participants were broadly accepting of the campaign messages. We identified a tendency toward quasi-libertarian leanings when discussing economics and trade, commercial versus personal responsibility, and the value of freedom (commercial and social). These perspectives were often held simultaneously with conflicting socially responsive values and references to the hegemonic position of "big business." This study affirms the importance of closely monitoring public opinion about tobacco control and of broadening denormalization strategies to reflect the critical role the tobacco industry plays in prolonging the tobacco epidemic. To date there is little evidence on the perceptions young adults hold toward to the tobacco industry and their arguments regarding the introduction of plain packaged cigarettes. Our findings indicate that some young people are attuned to the social discourse regarding the importance of economics, individuality, choice, and freedom as expressed by the tobacco industry. Tobacco control initiatives could challenge core values such as fairness and justice as related to corporate behaviors to retain public support, particularly among young people.


Synthesis, structure and photophysical properties of [UO2X2(O=PPh3)2] (X = Cl, Br, I).
The synthesis of a series of uranyl compounds via oxidation of [Li(THF)4][UX5(THF)] (X = Cl, Br, I) in the presence of Ph3P=O is described. The solid state structures of [Li(O=PPh3)(MeCN)2]2[UO2Cl4], [UO2Br2(O=PPh3)2] and [Li(O=PPh3)4][I3], formed as a by-product from the oxidation of [Li(THF)4][UI5(THF)], is reported. The electronic absorption spectra and photoluminescence spectra of [UO2X2(O=PPh3)2] (X = Cl, Br, I) have been measured and no significant changes in the position of the emission (515-530 nm) or the lifetimes (ca. 1 μs) are observed in this series. However a bathochromic shift is observed in the U-X LMCT band in the electronic absorption spectrum.


Defining Wound Healing Progression in Cetacean Skin: Characteristics of Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).
Cetaceans are tight-skinned mammals that exhibit an extraordinary capacity to heal deep soft tissue injuries. However, essential information of large full-thickness wound healing in cetaceans is still lacking. Here, the stages of full-thickness wound healing were characterized in Fraser's dolphins (Lagenodelphis hosei). The skin samples were collected from normal skin and full-thickness cookiecutter shark (Isistius brasiliensis)-bite wounds of stranded carcasses. We defined five stages of wound healing according to macroscopic and histopathological examinations. Wounds in Stage 1 and 2 were characterized by intercellular and intracellular edema in the epidermal cells near the wound edge, mixed inflammatory cell infiltration, and degradation of collagen fibers. In Stage 3 wounds, melanocytes, melanin granules, rete and dermal ridges were noticed in the neo-epidermis, and the adipose tissue in adjacent blubber was replaced by cells and fibers. Wounds in Stage 4 and 5 were characterized by gradual restoration of the normal skin architecture including rete and dermal ridges, collagen bundles, and adipose tissue. These phenomena were quite different from previous studies in terrestrial tight-skinned mammals, and therefore, further in-depth research into the mechanisms of dolphin wound healing would be needed to gain new insights into veterinary and human regenerative medicine.


Occupational exposures among personnel working near combined burn pit and incinerator operations at Bagram Airfield, Afghanistan.
Occupational air samples were collected at Bagram Airfield Afghanistan for security forces (SF) stationed at the perimeter of the solid waste disposal facility that included a burn pit, air curtain destructors, and solid waste and medical waste incinerators. The objective of the investigation was to quantify inhalation exposures of workers near the disposal facility. Occupational air sample analytes included total particulates not otherwise specified (PNOS), respirable PNOS, acrolein and polyaromatic hydrocarbons (PAH). Exposures were measured for four SF job specialties. Thirty 12-hour shifts were monitored from November 2011 to March 2012. The geometric means for respirable particulate matter and PAH for all job specialties were below the 12-hour adjusted American Conference of Governmental Industrial Hygienists threshold limit value time weighted averages (TLV-TWA). The geometric mean of the respirable particulate matter 12-hour TWAs for the four job specialties ranged from 0.116 to 0.134 mg/m(3). One measurement collected at the tower (3.1 mg/m(3)) position exceeded the TLV-TWA. Naphthalene and pyrene were the only PAHs detected in multiple samples of the 18 PAHs analyzed. The geometric mean concentration for naphthalene was 9.39E-4 mg/m(3) and the maximum concentration was 0.0051 mg/m(3). The geometric mean of acrolein for the four job specialties ranged from 0.021 to 0.047 mg/m(3). There were four exceedances of the Occupational Safety and Health Administration 8-hour permissible exposure limit- time weighted average (PEL-TWA), respectively, ranging from 0.13 to 0.32 mg/m(3).


Disparate cardiac effects of afterload reduction in hypertension.
Cardiac performance, as judged by preload, afterload, and myocardial contractility, was evaluated by non-invasive M-mode echocardiography before and after acute oral administration of calcium entry blockers (nitrendipine and verapamil), angiotensin converting enzyme (ACE) inhibitors (captopril and lisinopril), and a dopamine receptor agonist (fenoldopam) in patients with mild to moderate essential hypertension. Left ventricular end diastolic volume was taken as an index of preload, end systolic stress as an index of afterload, and the ratio of systolic pressure to end systolic volume (SBP:ESV), ejection fraction (EF), and mean velocity of circumferential fibre shortening (Vcf) as indices of contractility. Reductions of afterload and mean arterial pressure were achieved with all antihypertensive agents involved (mean percentage change +/- s.e.m.: 15 +/- 2% and 10 +/- 1%, respectively, P < 0.05) but the afterload reduction with lisinopril was greatest (21 +/- 9%; P < 0.01). The dopamine receptor agonist fenoldopam decreased by preload 24% (P < 0.05) and increased all of the three parameters of myocardial contractility (SBP:SV 66%; EF 17%, Vcf 19%; P < 0.01). In contrast, no effect on these parameters was observed with either calcium entry blocker or either ACE inhibitor.


Pulmonary sequestration with CCAM type II appearing as adrenal tumor protruding through a Bochdalek hernia.
A case of a pulmonary sequestration, which almost exclusively consisted of a congenital cystic adenomatoid malformation type II located subdiaphragmatically in the left retroperitoneal area, is reported. This case, in a 24-year-old male patient, is unique in that it appeared as an adrenal incidentaloma and extended through a Bochdalek hernia into the pleural space. It was discovered upon routine ultrasound screening for hepatocellular carcinoma in a patient with a carrier state for hepatitis B. Diagnosis was established only upon histological analysis of the surgically removed tumor after staining with hematoxylin and eosin as well as surfactant A and B. The location of the tumor may indicate that it was formed by an entrapment of a lung bud by the developing diaphragm. This appearance may give us insight into the formation of such tumors. It also highlights the difficulty of diagnosing subdiaphragmatic retroperitoneal tumors without histological examination.


The reported benefits of telehealth for rural Australians.
A literature review was conducted to identify the reported benefits attributed to telehealth for people living and professionals working in rural and remote areas of Australia. Scopus and relevant journals and websites were searched using the terms: telemedicine, telehealth, telepsychiatry, teledermatology, teleradiology, Australia, and each state and territory. Publications since 1998 were included. The initial search resulted in 176 articles, which was reduced to 143 when research reporting on Australian rural, regional or remote populations was selected. A narrative review was conducted using an existing 'benefits' framework. Patients are reported to have benefited from: lower costs and reduced inconvenience while accessing specialist health services; improved access to services and improved quality of clinical services. Health professionals are reported to have benefits from access to continuing education and professional development; provision of enhanced local services; experiential learning, networking and collaboration. Rural Australians have reportedly benefited from telehealth. The reported improved access and quality of clinical care available to rural Australians through telemedicine and telehealth may contribute to decreasing the urban-rural health disparities. The reported professional development opportunities and support from specialist through the use of telehealth may contribute to improved rural medical workforces recruitment and retention.