Climatic variation modulates the indirect effects of large herbivores on small-mammal habitat use.
Large mammalian herbivores (LMH) strongly shape the composition and architecture of plant communities. A growing literature shows that negative direct effects of LMH on vegetation frequently propagate to suppress the abundance of smaller consumers. Indirect effects of LMH on the behaviour of these consumers, however, have received comparatively little attention despite their potential ecological significance. We sought to understand (i) how LMH indirectly shape small-mammal habitat use by altering the density and distribution of understorey plants; (ii) how these effects vary with climatic context (here, seasonality in rainfall); and (iii) the extent to which behavioural responses of small mammals are contingent upon small-mammal density. We tested the effects of a diverse LMH community on small-mammal habitat use using 4 years of spatially explicit small-mammal trapping and vegetation data from the UHURU Experiment, a replicated set of LMH exclosures in semi-arid Kenyan savanna. Small-mammal habitat use was positively associated with tree density and negatively associated with bare (unvegetated) patches in all plots and seasons. In the presence of LMH, and especially during the dry season, small mammals consistently selected tree cover and avoided bare patches. In contrast, when LMH were excluded, small mammals were weakly associated with tree cover and did not avoid bare patches as strongly. These behavioural responses of small mammals were largely unaffected by changes in small-mammal density associated with LMH exclusion. Our results show that LMH indirectly affect small-mammal behaviour, and that these effects are influenced by climate and can arise via density-independent mechanisms. This raises the possibility that anthropogenic LMH declines might interact with changing patterns of rainfall to alter small-mammal distribution and behaviour, independent of numerical responses by small mammals to these perturbations. For example, increased rainfall in East Africa (as predicted in many recent climate-model simulations) may relax constraints on small-mammal distribution where LMH are rare or absent, whereas increased aridity and/or drought frequency may tighten them.


Does heparin rebound lead to postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass?
Heparin rebound is a common observed phenomenon after cardiac surgery with CPB and is associated with increased postoperative blood loss. However, the administration of extra protamine may lead to increased blood loss as well. Therefore, we want to investigate the relation between heparin rebound and postoperative blood loss and the necessity to provide extra protamine to reverse heparin rebound. We searched PubMed, Cochrane, EMBASE, Google Scholar and Web of Science to review the question: "Does heparin rebound lead to postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass." Combination of search words were framed within four major categories: heparin rebound, blood loss, cardiac surgery and cardiopulmonary bypass. All studies that met our question were included. Quality assessment was performed using the Cochrane risk of bias (RoB2) tool for randomized controlled trials and the risk of bias in non-randomized studies of intervention (ROBINS-I) for non-randomised trials. 4 randomized and 17 non-randomized studies were included. The mean incidence of heparin rebound was 40%. The postoperative heparin levels, due to heparin rebound, were often below or equal to 0.2 IU/mL. We could not demonstrate an association between heparin rebound and postoperative blood loss or transfusion requirements. However the quality of evidence was poor due to a broad variety of definitions of heparin rebound, measured by various coagulation tests and studies with small sample sizes. The influence of heparin rebound on postoperative bleeding seems to be negligible, but might get significant in conjunction with incomplete heparin reversal or other coagulopathies. For that reason, it might be useful to get a picture of the entire coagulation spectrum after cardiac surgery, as can be done by the use of a viscoelastic test in conjunction with an aggregometry test.


Trans-repression of gene activity upstream of T-DNA tagged RLK902 links Arabidopsis root growth inhibition and downy mildew resistance.
Receptor-like kinases (RLKs) constitute a large family of signal perception molecules in Arabidopsis. The largest group of RLKs is the leucine-rich repeat (LRR) class that has been described to function in development and defense. Of these, CLAVATA1 (CLV1) and ERECTA (ER) receptors function in maintaining shoot meristem homeostasis and organ growth, but LRR RLKs with similar function in the root remain unknown. For the interaction of Arabidopsis with the oomycete pathogen Hyaloperonospora arabidopsidis the involvement of LRR RLKs has not been demonstrated. A set of homozygous T-DNA insertion lines mutated in LRR RLKs was investigated to assess the potential role of these receptors in root meristem maintenance and compatibility. One mutant line, rlk902, was discovered that showed both reduced root growth and resistance to downy mildew in a recessive manner. The phenotypes of this mutated line could not be rescued by complementation, but are nevertheless linked to the T-DNA insertion. Microarray studies showed that gene expression spanning a region of approximately 84 kb upstream of the mutated gene was downregulated. The results suggest T-DNA mediated trans-repression of multiple genes upstream of the RLK902 locus links both phenotypes.


Indirect coupling of organic anion secretion to sodium in teleost (Paralichthys lethostigma) renal tubules.
Recent findings in both rat and crab indicate that renal accumulation of p-aminohippurate (PAH) across the basolateral membrane can be coupled indirectly to the Na gradient through PAH-glutarate exchange and Na/glutarate cotransport. However, the role of this mechanism in net transepithelial PAH secretion was not examined. Therefore, proximal tubules from Southern flounder kidney were used to assess both the presence of indirect coupling in the fish and its relationship to net secretion. [14C]glutarate uptake by proximal tubular masses was concentrative, Na dependent, and Li inhibitable. Glutarate efflux from preloaded masses was stimulated by addition of PAH to the medium. Thus flounder tubules exhibited both Na/glutarate uptake and glutarate-PAH exchange. Furthermore, steady-state [3H]PAH accumulation was increased 50% by 10-50 microM glutarate, and this increase was abolished by Li, indicating indirect coupling of PAH entry to Na. To determine whether indirect coupling affected net secretion as well as tissue accumulation, the steady-state accumulation of an anionic dye, fluorescein (FL), was measured in individual renal tubules by use of epifluorescence microscopy and video-image analysis. FL accumulated in tubules to levels that were 20-40 times higher than the medium. In most fish, luminal fluorescence was measurably higher than cellular, and uptake in both compartments was markedly reduced by PAH and Li. Moreover, FL accumulation in cells and lumina was increased by 70-100% when 50 microM glutarate was added to the bathing medium. Thus glutarate not only stimulated uphill FL entry into the cells, but also stimulated active secretion into the tubular lumen.(ABSTRACT TRUNCATED AT 250 WORDS)


Reactive oxygen species production in wheat roots is not linked with changes in h fluxes during acidic and aluminium stresses.
Aluminium stress induces peroxidation of lipids in the plasma membrane, the effect akin to that caused by reactive oxygen species (ROS). ROS have recently been proposed as regulators of redox-dependent ion transport across the plasma membrane during biotic and abiotic stresses, thus contributing to the plant defence system. The aim of this study was to discover whether ROS production is linked to redox-dependent H(+) transport system located at the plasma membranes of two near-isogenic lines of wheat (Triticum aestivum L., ET8 = Al-resistant, ES8 = Al-sensitive).The activities of NADPH-dependent ROS synthase and SOD were increased in both wheat lines 15 and 30 min after Al treatments. However, the ROS production was also increased under acidic stress. There was no difference between the two wheat lines in the root-cell plasma membrane capacity to efflux H(+) in response to potassium ferricyanide after Al and acidic treatments. In ET8, both stresses led to increases in ROS production and H(+) influx.ROS production in wheat seedlings was activated primarily by low pH exposure rather than by the Al stress. ROS production and breakdown in wheat seedlings under Al and acidic stresses appear to be linked to the intracellular metabolic changes rather than to the increased activity of plasma membrane-based NADPH-dependent ROS synthase.


Ablation of the cardiac-specific gene leucine-rich repeat containing 10 (Lrrc10) results in dilated cardiomyopathy.
Leucine-rich repeat containing 10 (LRRC10) is a cardiac-specific protein exclusively expressed in embryonic and adult cardiomyocytes. However, the role of LRRC10 in mammalian cardiac physiology remains unknown. To determine if LRRC10 is critical for cardiac function, Lrrc10-null (Lrrc10(-/-)) mice were analyzed. Lrrc10(-) (/-) mice exhibit prenatal systolic dysfunction and dilated cardiomyopathy in postnatal life. Importantly, Lrrc10(-/-) mice have diminished cardiac performance in utero, prior to ventricular dilation observed in young adults. We demonstrate that LRRC10 endogenously interacts with α-actinin and α-actin in the heart and all actin isoforms in vitro. Gene expression profiling of embryonic Lrrc10(-/-) hearts identified pathways and transcripts involved in regulation of the actin cytoskeleton to be significantly upregulated, implicating dysregulation of the actin cytoskeleton as an early defective molecular signal in the absence of LRRC10. In contrast, microarray analyses of adult Lrrc10(-/-) hearts identified upregulation of oxidative phosphorylation and cardiac muscle contraction pathways during the progression of dilated cardiomyopathy. Analyses of hypertrophic signal transduction pathways indicate increased active forms of Akt and PKCε in adult Lrrc10(-/-) hearts. Taken together, our data demonstrate that LRRC10 is essential for proper mammalian cardiac function. We identify Lrrc10 as a novel dilated cardiomyopathy candidate gene and the Lrrc10(-/-) mouse model as a unique system to investigate pediatric cardiomyopathy.


Ripped pocket and pickpocket, novel Drosophila DEG/ENaC subunits expressed in early development and in mechanosensory neurons.
Drosophila melanogaster has proven to be a good model for understanding the physiology of ion channels. We identified two novel Drosophila DEG/ ENaC proteins, Pickpocket (PPK) and Ripped Pocket (RPK). Both appear to be ion channel subunits. Expression of RPK generated multimeric Na+ channels that were dominantly activated by a mutation associated with neurodegeneration. Amiloride and gadolinium, which block mechanosensation in vivo, inhibited RPK channels. Although PPK did not form channels on its own, it associated with and reduced the current generated by a related human brain Na+ channel. RPK transcripts were abundant in early stage embryos, suggesting a role in development. In contrast, PPK was found in sensory dendrites of a subset of peripheral neurons in late stage embryos and early larvae. In insects, such multiple dendritic neurons play key roles in touch sensation and proprioception and their morphology resembles human mechanosensory free nerve endings. These results suggest that PPK may be a channel subunit involved in mechanosensation.


Loss of Uncoupling Protein 1 Expression in the Subcutaneous Adipose Tissue Predicts Childhood Obesity.
Stimulation of thermogenesis by inducing uncoupling protein 1 (UCP1) expression in adipocytes is thought to promote weight loss by increasing energy expenditure, and it is postulated that the human newborn has thermogenic subcutaneous fat depots. However, it remains unclear whether a relevant number of UCP1-expressing (UCP1+) adipocytes exist in the early postnatal life. Here we studied the distribution of UCP1 and the expression of thermogenic genes in the subcutaneous adipose tissues of the human fetus, infant and child. We show that the deep layer of human fetal and neonatal subcutaneous fat, particularly the abdominal wall, is rich in UCP1+ adipocytes. These adipocytes develop in the late third trimester and persist throughout childhood, expressing a panel of genes linked to mitochondrial biogenesis and thermogenesis. During the early childhood adiposity rebound-a critical phase that determines obesity risk later in life-the absence of adipose tissue UCP1 expression in children with normal body mass index (BMI) correlates with an obesity-associated gene expression signature. Finally, UCP1 expression is negatively correlated with BMI z-score and adipocyte size in infants and children. Overall, our results show that the absence of UCP1 expression in adipose tissue is an early indicator of adipose tissue expansion in children.


Muscle ammonia metabolism during isometric contraction in humans.
The changes in ammonia (NH3) and amino acid contents in human skeletal muscle during isometric exercise (2/3 maximal voluntary contraction force) to fatigue have been investigated. Biopsies from musculus quadriceps femoris were obtained at rest, fatigue, and 1 and 4 min recovery. Muscle NH3 (n = 9) increased from 1.3 +/- 0.3 (mean +/- SE) mmol/kg dry muscle (dm) at rest to 3.6 +/- 0.6 at fatigue (P less than 0.01) and remained elevated during recovery, whereas the lactate increase after contraction decreased rapidly during recovery. Total adenine nucleotide (TAN) content decreased from 28.7 +/- 0.5 mmol/kg dm at rest to 25.1 +/- 0.6 at fatigue (P less than 0.001). Muscle glutamine did not change after contraction (P greater than 0.05), whereas glutamate decreased (P less than 0.001), and alanine increased (P less than 0.001). In vivo AMP deaminase activity (measured by the rate of TAN decrease) was positively correlated with the percentage of fast-twitch fibers (r = 0.92; P less than 0.001) and the ATP turnover rate (r = 0.75; P less than 0.001) but was not related to the muscle lactate content (r = 0.27; P greater than 0.05). Phosphocreatine decreased to 6.1 +/- 0.7 mmol/kg dm (range = 1-11) after contraction. It is concluded that during exercise activation of AMP deaminase in vivo occurs when a high ATP turnover rate is coupled with a low phosphocreatine level, muscle pH is of minor importance for direct activation of AMP deaminase in vivo, and increases in NH3 do not have an important influence on glycolysis.


Effect of screw angulation on the bending performance of polyaxial locking interfaces: a micro-CT evaluation.
Polyaxial locking plates rely on a specific thread-to-thread interface of the screw head and the plate hole. The objective of this study was to evaluate the mechanical performance of single screw interfaces when inserted off-axis and to establish correlations between those parameters and the engagement of the screw head and the plate hole thread. Three polyaxial locking screw systems were inserted into the corresponding plates at various angles (0°, 5°, 10°, and 15° off-axis). The screws were tested until failure. A micro-CT was performed to examine the interface between the plate hole and the screw head. The standard insertion at 0° sustained the greatest maximum bending strength without relocation in the screw hole. Screws inserted at 15° showed a significant reduction in force of up to 44%, 55% and 57%, respectively. Micro-CT analysis of the interface showed a significant loss of thread engagement for off-axis insertion. Polyaxial plates offer additional advantages for off-axis placement of screws. However, this flexibility is related to a significant decrease in both thread engagement and bending strength compared to monoaxial insertion. Regardless the insertion angle, the loss of stability is comparable when screws are placed off-axis. Surgeons are advised to consider off-axis insertion as a salvage option, providing access to better bone stock.


Applying the benefits of the AwM study in the clinic.
The Act when Mild (AwM) Study has illustrated the benefits to migraineurs of taking triptan medication when their migraine pain is still mild and within 1 h of the onset of symptoms. Yet many patients wait until the attack has fully developed before taking their medication, with potentially inferior outcomes. In order to reproduce the benefits of early intervention using the AwM paradigm in daily practice, a number of key barriers need to be addressed at both the physician and patient level. Notable physician-related barriers to be overcome, particularly at the primary care level, include accuracy of an early diagnosis of migraine in newly presenting patients, communication skills that generate a therapeutic engagement with migraine patients and enhance patient confidence, the application of knowledge about up-to-date strategies to optimize treatment outcomes, and the setting of achievable goals to avoid unrealistic expectations. Patient-related obstacles that need to be identified and overcome encompass patient attitude, expectations, and behaviour. Migraine patients may be reluctant to consult their physician, and, of those who do, many stop consulting because they perceive that physicians can do little to improve their situation. For this reason, migraine patients need to be counselled about the most appropriate medication for their level of symptoms. Moreover, patients need to be confident before they will adhere routinely to the advice they receive, and high in the priority of advice is the use of medication, particularly triptans, at the first sign of a migraine attack, rather than waiting until their attack has progressed to moderate or severe intensity. Patients who adhere to this advice are likely to experience a notable reduction in the pain, disability and time lost that they would otherwise suffer. The beneficial effects of early triptan intervention illustrated in the AwM Study can therefore be best reproduced in the clinic if the correct advice given to patients is not only accepted and applied by them, but also followed up by their physician.


Key Components of the Complement Lectin Pathway Are Not Only Required for the Development of Inflammatory Arthritis but Also Regulate the Transcription of Factor D.
The complement system plays an important role in the pathogenesis of rheumatoid arthritis (RA). Besides driving lectin pathway (LP) activation, the mannan-binding lectin (MBL)-associated serine proteases (MASPs) also play a key role in regulating the alternative pathway (AP). We evaluated the effects of N-acetylgalactosamine (GalNAc)-conjugated MASP-1 and MASP-2 duplexes in vitro and in mice with and without arthritis to examine whether knockdown of MASP-1 and MASP-2 expression affects the development of arthritis. GalNAc-siRNAs for MASP-1 and MASP-2 demonstrated robust silencing of MASP-1 or MASP-2 at pM concentrations in vitro. To evaluate the impact of silencing in arthritic mice, we used the collagen antibody-induced arthritis (CAIA) mouse model of RA. Mice were injected a 10 mg/kg dose of GalNAc-siRNAs 3x s.q. prior to the induction of CAIA. Liver gene expression was examined using qRT-PCR, and protein levels were confirmed in the circulation by sandwich immunoassays and Western blot. At day 10, CAIA mice separately treated with MASP-1 and MASP-2 duplexes had a specific reduction in expression of liver MASP-1 (70-95%, p < 0.05) and MASP-2 (90%, p < 0.05) mRNA, respectively. MASP-1-siRNA treatment resulted in a 95% reduction in levels of MASP-1 protein in circulation with no effect on MASP-2 levels and clinical disease activity (CDA). In mice injected with MASP-2 duplex, there was a significant (p < 0.05) 90% decrease in ex vivo C4b deposition on mannan, with nearly complete elimination of MASP-2 in the circulation. MASP-2 silencing initially significantly decreased CDA by 60% but subsequently changed to a 40% decrease vs. control. Unexpectedly, GalNAc-siRNA-mediated knockdown of MASP-1 and MASP-2 revealed a marked effect of these proteins on the transcription of FD under normal physiological conditions, whereas LPS-induced inflammatory conditions reversed this effect on FD levels. LPS is recognized by Toll-like receptor 4 (TLR4), we found MBL not only binds to TLR4 an interaction with a Kd of 907 nM but also upregulated FD expression in differentiated adipocytes. We show that MASP-2 knockdown impairs the development of RA and that the interrelationship between proteins of the LP and the AP may extend to the transcriptional modulation of the FD gene.


[Nursing communication tool. A study to introduce a written model for communication between nursing staff of the surgical units and the operating rooms].
A study to introduce a nursing communication toot to make easier the continuity of nursing care of the surgical patient in the pre, per and postoperative periods. The communication tool consists in two parts: preoperative and peroperative notes form. This tool was aplied to 327 patients undergoing surgical treatment who were interned in three general surgical units and in three specialized units in a general hospital. The application of the tool was made by nursing staff of the surgical units and the operating room of the hospital. It was verified, by the analysis of results, that the frequency of the filling-in items on the preoperative form was higher than 83%, above the 70% established in this present study. The percentage of items registered on the peroperative form was above 85%, excepting pulse rate and blood pressure that showed less than 70%. The frequency of the filling-in of the items on the two forms, preoperative and peroperative, was analyzed separately for each six surgical units. The percentual variation of the filling-in was between 83 and 100% which makes possible the inference that this nursing communication tool is certainly applicable to patients undergoing general specialized surgery.


[Halo-fixator vest--indications and complications].
Over the period between 06/00 and 03/03, 41 patients with different injuries of the upper cervical spine were treated by a halo fixator and were statistically recorded. The collective showed different injury patterns, 2 fractures of occiput condyles (5%), 3 Jefferson fractures (7%), 1 combined injury of the odontoid process and an atlas fracture (2%), 32 odontoid fractures (78%), 2 hanged-man-fractures Typ Effendi II (5%) and one case of pathologic fractures from the 2. to the 4. cervical vertebral body based on a plasmocytoma (2%). 31 of 41 patients could be examined for a follow up; 40 complete medical histories were well documented and could be analysed. As complications we had screw loosening in 6 cases (15%), a complete tear out of screws in 2 cases (5%). One patient took the halo away by himself two times, so after the second time surgical stabilisation was performed (2,5%). One case of intracranial penetration of a screw happened after the patient fell down in an accident with the halo (2,5%). Infection of the screw pins appeared in 4 cases (10%) and we had 2 cases of skin necrosis (5%). A second reduction after redisplacement was necessary in 8 cases (20%). 23 patients suffered from pain at the insertion of the screws (75%) and 18 patients complained of pressure in the head (58%). On the question of the comfort of this kind of therapy answered 18 patients with "intolerable" (58%), 10 patients with middle (32%) and 3 patients with tolerable (10%). Despite of the large number of different complications and the miscomfort of a halo fixator we think that there are still indications for treatment of special injuries of the upper cervical spine with a halo fixator. One important aspect is the lack of adequate alternatives even with regard to the biomechanical stability.


New vaccine technologies.
New vaccine development for potential use in human medicine is buoyant. New science (genomics and proteomics) is presenting major new opportunities. New approaches (DNA vaccines, new combination vaccines, new formulations, novel delivery routes, new adjuvants) are being vigorously explored. New needs (defence vaccines) are being identified. One common element in all these varied areas is that pre-clinical evaluation of a candidate new vaccine is a pre-requisite before initiation of clinical trials in humans. Laboratory evaluation also usually continues during the clinical phase of vaccine development. Pre-clinical and laboratory evaluations often involve animals. Data from these studies are used to support an application for marketing authorisation. Regulatory Authorities use precedent to help assess these applications. Where no precedent exists the Regulatory Authorities apply risk-benefit analyses based on the perceived risks of a new product or process. These perceived risks are constantly reviewed as experience is gained. The World Health Organisation facilitates the development of scientific consensus on issues that have an impact on the quality and safety of biological medicines, including vaccines. New vaccine technologies often present new challenges for the safety and efficacy evaluation of candidate preparations. Animal models are usually very important in this process. The number of new vaccine candidates seems set to increase in the short-term.


Solubilization of bovine heart-value collagen.
Complete solubilization of bovine heart-valve gollagen was obtained by using sequential pepsin digestion and extraction with dithiothreitol under non-denaturing conditions. Use of the reducing agent was the crucial step resulting in solubilization. These findings suggest that disulphide-bonded proteins may be in part responsible for the insolubility of bovine heart-valve collagen.


[Delayed behavioral and morphological consequences in activation of the stress-antistress system in early ontogeny stages in rats].
Wistar rat pups aged 4-10-17 days were injected intraperitoneally with corticoliberin (corticotrophin-releasing hormone, CRH) in doses of 0.5 - 1.0 - 2.0 mg/rat, respectively (single administration for each rat), which activates the stress system, or with 70-kDa heat-shock protein (HSP-70) in doses of 5 - 10 - 20 mg/rat, respectively, which plays the role of intracellular shaperons and possesses antistress properties. The effect of drugs on the emotional and motor behavior was assessed in 5 tests (open field, elevated plus-maze, intruder-resident, Porsolt's depression test, and rotation test) in adult rats 90- 100-days-old. The activation of stress or antistress systems by CRH or HSP-70, respectively, changed the behavior of adult rats. These effects depended on the animal gender, being different in males and females: male rats were more sensitive in Porsolt's depression test, elevated plus-maze anxiety test, and rotation test, while being less sensitive in the open field and intruder-resident tests. These results indicate that the initial sensitivity of males and females with respect to CRH and HSP-70 is also different. The experimental data exhibited correlation with the results of morphological investigation of the limbic structures of the brain. In particular, CRH increased the relief (volume) of neurons of substantia nigra and ventral tegmental region without changing their density, while HSP-70 produced moderate degeneration of neurons and decreased their density. It is suggested the obtained data have to be taken into account in planning and conducting experimental investigations devoted to the influence of various pharmacological agents on the behavior.


Multiresolution registration of remote sensing imagery by optimization of mutual information using a stochastic gradient.
Image registration is the process by which we determine a transformation that provides the most accurate match between two images. The search for the matching transformation can be automated with the use of a suitable metric, but it can be very time-consuming and tedious. We introduce a registration algorithm that combines a simple yet powerful search strategy based on a stochastic gradient with two similarity measures, correlation and mutual information, together with a wavelet-based multiresolution pyramid. We limit our study to pairs of images, which are misaligned by rotation and/or translation, and present two main results. First, we demonstrate that, in our application, mutual information may be better suited for sub-pixel registration as it produces consistently sharper optimum peaks than correlation. Then, we show that the stochastic gradient search combined with either measure produces accurate results when applied to synthetic data, as well as to multitemporal or multisensor collections of satellite data. Mutual information is generally found to optimize with one-third the number of iterations required by correlation. Results also show that a multiresolution implementation of the algorithm yields significant improvements in terms of both speed and robustness over a single-resolution implementation.


[Effect of some polycyclic aromatic hydrocarbons on gap junction intercellular communication in hepatoma Hep G2 cell culture].
Systems regulating tissue homeostasis are gap junction intercellular communications (GJIC). It is accepted that the down-regulation of GJIP has been due to tumor promoting properties of carcinogens. In this study, effects of some carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons (PAH) on GJIC were investigated. Noncarcinogenic PAHs do not influence GJIC function. In dose 5 microg/ml carcinogenic PAHs down-regulated GJIC by 70-100% after a 24 h treatment. Dependent on the structure of PAHs, down-regulation was observed after a 1 h treatment. The methyl group in PAH structure decreased down-regulation of GJIC in 1 h experiments, whereas after a 24 h treatment the down-regulation caused by methyl group either contained or not contained PAH was nearly the same. To clarify the role of Ah-receptor in PAH action on GJIC, the effect of 2,3,7,8-tetrachlorodibezdioxin, a specific ligand of Ah-receptor was studied, which appeared to be insignificant. Benzo/a/pyrene does not influence the functioning of gramicidine channels formed in the phospholipid membrane. This result indicates that PAH action on GJIC is not associated with non-specific destruction of the membrane. Thus, two steps are there in PAH action on GJIC: one is fast and caused by specific interaction of unchanged PAH molecule, the other develops in time and is presumably associated with the formation of active metabolites.


Four new species of coccidia (Apicomplexa: Eimeriidae) from Owen Stanley Skinks, Papuascincus stanleyanus (Sauria: Scincidae), from Papua New Guinea.
Between September and November 1991, 12 Owen Stanley skinks, Papuascincus stanleyanus (Booulenger) were collected from various localities on Papua New Guinea and examined for coccidians. Six (50%) were found to harbour four eimerians that we describe here as new. Oocysts of Eimeria burseyi sp. n. were elongate to ellipsoidal with a bilayered wall and measured (length x width, L x W) 36.0 x 24.0 microm, with a L/W ratio of 1.5. Both micropyle and oocyst residuum were absent, but a polar granule was present. Oocysts of Eimeria goldbergi sp. n. were ellipsoidal, with a bilayered wall, and measured 21.4 x 16.1 microm; L/W ratio was 1.3. Both micropyle and oocyst residuum were absent, but a single or fragmented polar granule was present. Oocysts of Eimeria boulengeri sp. n. were spheroidal to slightly subspheroidal, with a thin, single-layered wall that readily collapses, and measured 16.0 microm, L/W ratio was 1.0. Both micropyle and oocyst residuum were absent, but usually one (sometimes two) polar granule(s) were present. Oocysts of Eimeria niuginiensis sp. n. were oblong to tapered with a bilayered wall, and measured 20.0 x 13.1 microm; L/W ratio was 1.5. A micropyle, oocyst residuum and polar granule were absent. To our knowledge, these represent the only coccidians ever described from P. stanleyanus.


Association between periodontitis stages and self-reported diseases in a Norwegian population: the HUNT study.
The relationships between periodontitis and non-communicable diseases (NCDs) have been investigated through several different case-definitions. The differences in methodology may have hindered the basis of comparison between these studies. The classification from the 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions offers a unison platform that may facilitate future comparison of such research. The present study aimed to reproduce associations between periodontitis and other NCDs using the 2017 Classification, in the Trøndelag Health Study (HUNT). The fourth HUNT-survey was carried out between 2017 and 2019. Clinical variables, blood samples and answers to questionnaires were collected from 4933 participants. Periodontal status was assessed based on the latest staging system, and its associations with NCDs were estimated by logistic regression models adjusted for potential confounders. Compared to no or Stage I periodontitis, participants with Stage III/IV periodontitis (radiographic bone loss exceeding 33%) were associated with cardiovascular disease, hyperglycemia in participants with diabetes and chronic obstructive pulmonary disease (COPD)/emphysema. Associations with hyperglycemia in participants with diabetes and COPD/emphysema were also observed in participants with Stage II periodontitis. The only observed association when considering never-smokers alone, was with COPD/emphysema. Periodontitis Stage II and III/IV were associated with major NCDs. Effect sizes increased with increasing periodontitis stages, which implies greater occurrence of coincident comorbidities in patients with severe periodontitis.


Technical note: Dental microwear textures of "Phase I" and "Phase II" facets.
The power stroke of mastication has been traditionally divided into two parts, one which precedes centric occlusion, and the other which follows it-"Phase I" and "Phase II," respectively. Recent studies of primate mastication have called into question the role of Phase II in food processing, as they have found little muscle activity or accompanying bone strain following centric occlusion. That said, many researchers today look to Phase II facets to relate diet to patterns of dental microwear. This suggests the need to reevaluate microwear patterns on Phase I facets. Here we use texture analysis to compare and contrast microwear on facets representing both phases in three primate species with differing diets (Alouatta palliata, Cebus apella, and Lophocebus albigena). Results reaffirm that microwear patterns on Phase II facets better distinguish taxa with differing diets than do those on Phase I facets. Further, differences in microwear textures between facet types for a given taxon may themselves reflect diet. Some possible explanations for differences in microwear textures between facet types are proposed.


Macrophage depletion abates Porphyromonas gingivalis-induced alveolar bone resorption in mice.
The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80(+) macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80(+) macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis-induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis-specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-γ, and IL-12 (p70)] responses were significantly (p < 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86(+)), rather than M2 macrophages (CD206(+)), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1β, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-α and -β, and TNF-α in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.


A novel herpesvirus associated with respiratory disease in Bourke's parrots (Neopsephotus bourkii).
A novel herpesvirus infection in nine Bourke's parrots (Neopsephotus bourkii, formerly Neophema bourkii) housed in an outdoor aviary comprised of multiple species of birds was diagnosed based on histopathology, electron microscopy and polymerase chain reaction (PCR). Clinical signs in the parrots included anorexia, ruffled feathers, depression, loss of weight and respiratory distress. The most common gross lesions were moderately congested and oedematous lungs and a mild fibrinous exudate in the air sacs and lumen of the trachea. Histological examination revealed mild to severe bronchopneumonia and airsacculitis with syncytial cells containing eosinophilic intranuclear inclusion bodies in most birds. Other less frequent changes included tracheitis, syringitis, sinusitis, rhinitis, otitis media and conjunctivitis. Attempts to culture the virus in chicken embryos and chicken embryo liver cells were unsuccessful. Examination by transmission electron microscopy of syncytial cells from the lungs of two birds revealed intranuclear virus particles typical of the family Herpesviridae. DNA from a novel herpesvirus was amplified from lung tissue by PCR using degenerate primers derived from conserved avian herpesvirus sequences. The virus belongs in the genus Iltovirus of the Alphaherpesvirinae subfamily. It is not closely related to Psittacid herpesvirus 1 that causes Pacheco's disease but does group phylogenetically with a clade of herpesviruses that cause respiratory disease in a number of avian species. The proposed name for this herpesvirus is Psittacid herpesvirus 3.


Moment arms about the carpal and metacarpophalangeal joints for flexor and extensor muscles in equine forelimbs.
To determine whether muscle moment arms at the carpal and metacarpophalangeal joints can be modeled as fixed-radius pulleys for the range of motion associated with the stance phase of the gait in equine forelimbs. 4 cadaveric forelimbs from 2 healthy Thoroughbreds. Thin wire cables were sutured at the musculotendinous junction of 9 forelimb muscles. The cables passed through eyelets at each muscle's origin, wrapped around single-turn potentiometers, and were loaded. Tendon excursions, measured as the changes in lengths of the cables, were recorded during manual rotation of the carpal (180 degrees to 70 degrees) and metacarpophalangeal (220 degrees to 110 degrees) joints. Extension of the metacarpophalangeal joint (180 degrees and 220 degrees) was forced with an independent loading frame. Joint angle was monitored with a calibrated potentiometer. Moment arms were calculated from the slopes of the muscle length versus joint angle curves. At the metacarpophalangeal joint, digital flexor muscle moment arms changed in magnitude by < or = 38% during metacarpophalangeal joint extension. Extensor muscle moment arms at the carpal and metacarpophalangeal joints also varied (< or = 41% at the carpus) over the range of joint motion associated with the stance phase of the gait. Our findings suggest that, apart from the carpal flexor muscles, muscle moment arms in equine forelimbs cannot be modeled as fixed-radius pulleys. Assuming that muscle moment arms at the carpal and metacarpophalangeal joints have constant magnitudes may lead to erroneous estimates of muscle forces in equine forelimbs.


Knot Formation on DNA Pushed Inside Chiral Nanochannels.
We performed coarse-grained molecular dynamics simulations of DNA polymers pushed inside infinite open chiral and achiral channels. We investigated the behavior of the polymer metrics in terms of span, monomer distributions and changes of topological state of the polymer in the channels. We also compared the regime of pushing a polymer inside the infinite channel to the case of polymer compression in finite channels of knot factories investigated in earlier works. We observed that the compression in the open channels affects the polymer metrics to different extents in chiral and achiral channels. We also observed that the chiral channels give rise to the formation of equichiral knots with the same handedness as the handedness of the chiral channels.


[The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome: a case report].
The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome is an entity characterized by clinical, analytical, immunological and histological manifestations of both entities. We present the case of a 26-year-old woman with a serious acute hepatitis that fulfills the diagnostic criteria of the overlap syndrome and that showed a satisfactory response to oral corticoid therapy.


Prevalence of asthma and respiratory symptoms in south-central Durban, South Africa.
The prevalence of asthma and respiratory symptoms in south-central Durban, one of the most heavily polluted areas of South Africa, has been determined using a cross-sectional survey of 213 households in the communities of Merewent (97% Indians) and Austerville (98% coloreds). The study population consisted of 367 children (less than 17 years old) and 693 adults. About 10% of the children and 12% of adults reported doctor diagnosed asthma. The self-reported prevalence rates for wheezing (3740%) and attacks of shortness of breath with wheeze (16-28%) were much higher than that for doctor diagnosed asthma and common co-occurrence of the three symptoms is found. The prevalence rates for other respiratory symptoms include 33-35% for chronic cough, 31-32% for chronic phlegm, 44-50% for frequent blocked-runny nose, and 16-27% for sinusitis. Factors in the community that were associated with asthma, wheeze and shortness of breath with wheeze among the adult population included cigarette smoking, use of insecticides (coils and pump spray) and home ownership. An association between asthma among children and a number of household risk factors including dampness, carpet, pets or use of pesticides was not apparent in the community. Asthma prevalence was strongly correlated with missing of school by children (odds ratio (OR): 44; 95% confidence interval (CI): 13-141). The study serves to draw attention to a growing but neglected public health problem in urban areas of Africa.


Hydrogen Water Drinking Exerts Antifatigue Effects in Chronic Forced Swimming Mice via Antioxidative and Anti-Inflammatory Activities.
This study was performed to evaluate antifatigue effect of hydrogen water (HW) drinking in chronic forced exercise mice model. Twelve-week-old C57BL6 female mice were divided into nonstressed normal control (NC) group and stressed group: (purified water/PW-treated group and HW-treated group). Stressed groups were supplied with PW and HW, respectively, ad libitum and forced to swim for the stress induction every day for 4 consecutive weeks. Gross antifatigue effects of HW were assessed by swimming endurance capacity (once weekly for 4 wk), metabolic activities, and immune-redox activities. Metabolic activities such as blood glucose, lactate, glycogen, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) as well as immune-redox activities such as reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), catalase, and the related cytokines were evaluated to elucidate underlying mechanism. Blood glucose and lactate were measured at 0 wk (before swimming) and 4 wk (after swimming). HW group showed a higher swimming endurance capacity (p < 0.001) than NC and PW groups. Positive metabolic effects in HW group were revealed by the significant reduction of blood glucose, lactate, and BUN in serum after 4 wk (p < 0.01, resp.), as well as the significant increase of liver glycogen (p < 0.001) and serum LDH (p < 0.05) than PW group. In parallel, redox balance was represented by lower NO in serum (p < 0.01) and increased level of GPx in both serum and liver (p < 0.05) than PW group. In line, the decreased levels of serum TNF-α (p < 0.01), IL-6, IL-17, and liver IL-1β (p < 0.05) in HW group revealed positive cytokine profile compared to PW and NC group. This study shows antifatigue effects of HW drinking in chronic forced swimming mice via metabolic coordination and immune-redox balance. In that context, drinking HW could be applied to the alternative and safety fluid remedy for chronic fatigue control.


Droplet Exposure Risk to Providers From In-Office Flexible Laryngoscopy: A COVID-19 Simulation.
To provide data on risk of respiratory droplets from common otolaryngologic procedures during the COVID-19 pandemic, a novel simulation of droplet exposure from flexible laryngoscopy was performed. After completion of a nasal symptom questionnaire, topical fluorescein spray was administered into the nasal and oropharynx of 10 healthy volunteers, who then underwent flexible laryngoscopy under 2 conditions: routine without provoked response and with prompted sneeze/cough. After each, droplets on the proceduralist and participant were counted under ultraviolet A light. Droplets were observed on 1 of 10 volunteers after routine laryngoscopy and 4 of 10 during laryngoscopy with sneeze/cough. A nasal symptom score based on congestion and rhinorrhea was significantly elevated among droplet producers after sneeze/cough (P = .0164). No droplets were observed on the provider. Overall, with adequate personal protective equipment, flexible laryngoscopy poses minimal droplet risk to providers. Nasal symptoms can identify patients more likely to produce droplets after sneeze/cough.


Slow synaptic excitation in sympathetic ganglion cells: evidence for synaptic inactivation of potassium conductance.
The slow excitatory postsynaptic potential (EPSP) was investigated in frog sympathetic ganglion cells. In contrast to the increased conductance associated with other known EPSP's, during the slow EPSP resting membrane conductance was decreased. Electrical depolarization of the membrane potentiated the slow EPSP, whereas progressive hyperpolarization decreased its size and then reversed it to a hyperpolarizing potential (the opposite of the effect of membrane polarization on other EPSP's). The reversal potential of the slow EPSP was close to the potassium equilibrium potential. We propose that the slow EPSP, in contrast to classical EPSP's, is generated by an inactivation of resting potassium conductance.


Isolation and sequencing of the Epstein-Barr virus BNLF-1 gene (LMP1) from a Chinese nasopharyngeal carcinoma.
The BamHI fragment containing the Epstein-Barr virus (EBV) LMP1 gene was cloned from a genomic library of the nude mouse-propagated Chinese nasopharyngeal carcinoma CAO. The sequence of the LMP1 gene and its promoter and enhancer was determined. The nucleotide sequence of the CAO isolate differed from those of the B95-8 and Raji isolates in the promoter/enhancer region; the amino acid sequence of the protein also differed. Structural differences in the protein were located mainly in the 20 N-terminal residues and the array of repeated amino acids in the C-terminal part of the protein, in which the CAO isolate displays a cluster of seven perfect repeats of 11 amino acids (aa). Three of these repeats have no counterpart in the other virus strains. This, together with two deletions of five and 10 aa in the C-terminal part, yields a protein of 404 aa, compared to 386 aa for B95-8 and Raji. The larger LMP1 protein was detected on immunoblots of tissue samples from the CAO nude mouse tumour, and was also present in EBV-negative B cell lines and immortalized keratinocytes transfected with the cloned gene. A XhoI restriction site in exon 1 of the B95-8 BNLF-1 gene was absent from the CAO EBV isolate, as well as from 36 of 37 Chinese NPC biopsies tested. In contrast, 17 of 19 NPC biopsies of African origin retained this XhoI site.


Making noncatastrophic health care processes reliable: Learning to walk before running in creating high-reliability organizations.
Health care clinicians successfully apply proven medical evidence in common acute, chronic, or preventive care processes less than 80 percent of the time. This low level of reliability at the basic process level means that health care's efforts to improve reliability start from a different baseline from most other industries, and therefore may require a different approach. This paper describes The Institute for Healthcare Improvement's (IHI) current approach to improving health care reliability, including a useful nomenclature for levels of reliability, and a focus on improving reliability of basic health care processes before moving on to more sophisticated high reliability organization concepts. Early IHI work with a community of health care reliability innovators has identified four themes in health care settings that help to explain at least a portion of the gap in process reliability between health care and other industries. These include extreme dependence on hard work and personal vigilance, a focus on mediocre benchmark outcomes rather than process, great tolerance of provider autonomy, and failure to create systems that are specifically designed to reach articulated reliability goals. This paper describes our recommendations for the initial steps health care organizations' might take, based on these four themes, as they begin to move toward higher reliability.


Use of Electronic Consultation System to Improve Access to Care in Pediatric Hematology/Oncology.
Electronic consultations (eConsult) allow for communication between primary care providers and specialists in an asynchronous manner. This study examined provider satisfaction, topics of interest, and efficiency of eConsult in pediatric hematology/oncology in Ottawa, Canada. We conducted a cross-sectional assessment of all eConsult cases directed to pediatric hematology/oncology specialists using the Champlain BASE (Building Access to Specialists through eConsultation) eConsult service from June 1, 2014 to May 31, 2016. There were 1064 eConsults to pediatrics during the study timeperiod and pediatric hematology/oncology consults accounted for 8% (85). During the same study timeperiod, 524 consults were seen in the pediatric hematology/oncology clinic. The majority of the eConsults were for hematology (90.5%) in contrast to oncology topics (9.5%). The most common topics were anemia, hemoglobinopathy, bleeding disorder, and thrombotic state. Primary care providers rated the eConsult service very highly, and their comments were very positive. The eConsult service resulted in deferral of 40% of consults originally contemplated to require a face-to-face specialist visit. This study showed successful implementation and use of the eConsult service for pediatric hematology/oncology and resulted in avoidance of a large number of face-to-face consultation. The common topics identified areas for continuing medical education.


Mutational analysis of the "regulatory module" of hormone-sensitive lipase.
Hormone-sensitive lipase (HSL) is a rate-limiting enzyme in lipolysis that displays broad substrate specificity. HSL function is regulated by reversible phosphorylation that occurs within a 150 aa "regulatory module" of the protein. The current studies used mutational analysis to dissect the contribution of the "regulatory module" in HSL activity and substrate specificity. Deletion of the entire "regulatory module" or replacement of the "regulatory module" with the "lid" of lipoprotein lipase resulted in enzymatically inactive proteins. Deletion of sequentially longer stretches of the "regulatory module" resulted in a stepwise reduction in hydrolytic activity. Analysis of 7-19 amino acid deletional mutants that spanned the "regulatory module" showed that the N-terminal partial deletion mutants retained normal hydrolytic activity and activation by PKA. In contrast, the C-terminal partial deletion mutants displayed reduced hydrolytic activities, with preferential loss of activity against lipid-, as opposed to water-soluble, substrates. Single amino acid mutations of F650C, P651A, and F654D reduced activity against lipid-, but not water-soluble, substrates. The current results suggest that the length of the "regulatory module" and specific sequences within the C-terminal portion of the "regulatory module" of HSL (amino acids 644-683) are crucial for activity and appear to be responsible for determining lipase activity.


Patient Trust in Physicians: Empirical Evidence from Shanghai, China.
Patient trust in physicians, which can be considered a collective good, is necessary for an effective health care system. However, there is a widespread concern that patient trust in physicians is declining under various threats to the physician-patient relationship worldwide. This article aimed to assess patient trust in physicians through a quantitative study in Shanghai, China, and to provide appropriate suggestions for improving the trust in China. The data from a survey conducted in Zhongshan Hospital and Shanghai Tenth People's Hospital, which are two tertiary public hospitals in Shanghai, were used in this study. Patient trust in physicians was the dependent variable. Furthermore, a 10-item scale was used to precisely describe the dependent variable. The demographic characteristics were independent variables of trust in physicians. Binomial logistic regression was employed to analyze the factors associated with the dependent variable, which was divided into two categories on the basis of the responses (1: Strongly agree or agree and 0: Strongly disagree, disagree, or neutral). This study found that 67% of patients trusted or strongly trusted physicians. The mean score of patient trust in physicians was 35.4 from a total score of 50. Furthermore, patient trust in physicians was significantly correlated with the age, education level, annual income, and health insurance coverage of the patients. Patient trust in physicians in Shanghai, China is higher than previously reported. Furthermore, the most crucial reason for patient distrust in physicians is the information asymmetry between patients and physicians, which is a natural property of the physician-patient relationship, rather than the so-called for-profit characteristic of physicians or patients' excessive expectations.


Prevalence of Clostridium botulinum in fishes from markets in Osaka.
A total of 142 samples of different sea foods, mostly fish, were procured from the near-by supermarkets to examine the edible parts for the presence of Clostridium botulinum. Eleven samples (7.7%) seemed to contain this organism. Of these samples, we identified the toxin type in seven; six were type C and the other one type D. Isolation of C. botulinum type C was successful form the six samples but that of type D failed.


Combining conventional technique with fluoroscopy integration module in accessory pathway ablation.
Accessory pathway (AP) ablation is a straightforward approach with high success rates, but the fluoroscopy time (FT) is significantly longer in conventional technique. Electroanatomical mapping systems (EMS), reduce the FT, but anatomical and activation mapping may prolong the procedure time (PT). The fluoroscopy integration module (FIM) uses prerecorded fluoroscopy images and allows ablation similar to conventional technique without creating an anatomical map. In this study, we investigated the effects of combining the FIM with traditional technique on PT, success, and radiation exposure. A total of 131 patients who had undergone AP ablation were included in our study. In 37 patients, right and left anterior oblique (RAO-LAO) images were acquired after catheter placement and integrated with the FIM. The ablation procedure was then similar to the conventional technique, but without the use of fluoroscopy. For the purpose of acceleration, anatomical and activation maps have not been created. Contact-force catheters were not used. 94 patients underwent conventional ablation using fluoroscopy only. FIM into AP ablation procedures led to a significant reduction in radiation exposure, lowering FT from 7.4 to 2.8 min (p < .001) and dose-area product from 12.47 to 5.8 μGym² (p < .001). While the FIM group experienced a reasonable longer PT (69 vs. 50 min p < .001). FIM reduces FT regardless of operator experience and location of APs CONCLUSION: Combining FIM integration with conventional AP ablation offers reduced radiation exposure without compromising success rates and complication.


Portrait of an enzyme, a complete structural analysis of a multimodular {beta}-N-acetylglucosaminidase from Clostridium perfringens.
Common features of the extracellular carbohydrate-active virulence factors involved in host-pathogen interactions are their large sizes and modular complexities. This has made them recalcitrant to structural analysis, and therefore our understanding of the significance of modularity in these important proteins is lagging. Clostridium perfringens is a prevalent human pathogen that harbors a wide array of large, extracellular carbohydrate-active enzymes and is an excellent and relevant model system to approach this problem. Here we describe the complete structure of C. perfringens GH84C (NagJ), a 1001-amino acid multimodular homolog of the C. perfringens micro-toxin, which was determined using a combination of small angle x-ray scattering and x-ray crystallography. The resulting structure reveals unprecedented insight into how catalysis, carbohydrate-specific adherence, and the formation of molecular complexes with other enzymes via an ultra-tight protein-protein interaction are spatially coordinated in an enzyme involved in a host-pathogen interaction.


Characterization of human anti-high molecular weight-melanoma-associated antigen single-chain Fv fragments isolated from a phage display antibody library.
The human high molecular weight-melanoma-associated antigen (HMW-MAA) meets the criteria to be used as an immunogen for immunotherapy of malignant melanoma, because it is expressed by a large percentage of melanoma lesions with limited heterogeneity and has a restricted distribution in normal tissues. The high immunogenicity of the HMW-MAA in BALB/c mice has resulted in the development of a large number of anti-HMW-MAA monoclonal antibodies (mAbs). In contrast, no human anti-HMW-MAA mAbs have been described. Because the latter may serve as useful probes to characterize the antigenic profile of the HMW-MAA, human anti-HMW-MAA single-chain fragments of the variable region (scFvs) were isolated by panning synthetic scFv library 1 on purified HMW-MAA. Colony hybridization studies and nucleotide sequence analysis revealed that scFv 19, 44, 56, and 61 belong to the V(H)3 gene family and use the DP-38 germ-line gene segment but have a diverse third complementarity-determining region. The human scFvs share some characteristics with mouse anti-HMW-MAA mAb but also display some distinct features. Like mouse mAbs, human scFvs recognize determinants of HMW-MAA with a heterogeneous cellular and molecular distribution in human melanoma cells. Furthermore, like some mouse mAbs, human scFvs react with rat neural cells expressing the chondroitin sulfate proteoglycan NG2, which shows 81% homology to the HMW-MAA. However, at variance with mouse mAbs, the human scFvs show poor reactivity with guinea pig melanoma cells. Lastly, human scFv 61 stains both benign and malignant lesions of melanocytic origin, although with a lower frequency than mouse mAbs. Analysis of the clinical significance of the differential expression of the scFv 61-defined determinant in melanoma lesions will be facilitated by its reactivity with formalin-fixed melanoma lesions. In contrast to mouse mAb, scFv 61 immunoprecipitates the >450-kDa chondroitin sulfate proteoglycan component of the HMW-MAA, but not its 250-kDa subunit from melanoma cells. Thus, contrary to the current view about the structure of HMW-MAA, our results demonstrate that the two components are not associated. The described scFv antibodies, which represent the first example of human anti-HMW-MAA antibodies, have provided novel information about the structure of this antigen. Future studies will assess the impact of these in vitro-assembled antibody fragments on the identification of antigenic determinants of the HMW-MAA that can be recognized by the human immune system.


Electrophysiological correlates of the BOLD signal for EEG-informed fMRI.
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG-fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological-haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG-fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG-fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG-fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations.


The Chemical Interplay between Nitric Oxide and Mitochondrial Cytochrome c Oxidase: Reactions, Effectors and Pathophysiology.
Nitric oxide (NO) reacts with Complex I and cytochrome c oxidase (CcOX, Complex IV), inducing detrimental or cytoprotective effects. Two alternative reaction pathways (PWs) have been described whereby NO reacts with CcOX, producing either a relatively labile nitrite-bound derivative (CcOX-NO(2) (-), PW1) or a more stable nitrosyl-derivative (CcOX-NO, PW2). The two derivatives are both inhibited, displaying different persistency and O(2) competitiveness. In the mitochondrion, during turnover with O(2), one pathway prevails over the other one depending on NO, cytochrome c(2+) and O(2) concentration. High cytochrome c(2+), and low O(2) proved to be crucial in favoring CcOX nitrosylation, whereas under-standard cell-culture conditions formation of the nitrite derivative prevails. All together, these findings suggest that NO can modulate physiologically the mitochondrial respiratory/OXPHOS efficiency, eventually being converted to nitrite by CcOX, without cell detrimental effects. It is worthy to point out that nitrite, far from being a simple oxidation byproduct, represents a source of NO particularly important in view of the NO cell homeostasis, the NO production depends on the NO synthases whose activity is controlled by different stimuli/effectors; relevant to its bioavailability, NO is also produced by recycling cell/body nitrite. Bioenergetic parameters, such as mitochondrial ΔΨ, lactate, and ATP production, have been assayed in several cell lines, in the presence of endogenous or exogenous NO and the evidence collected suggests a crucial interplay between CcOX and NO with important energetic implications.


Integrating family planning services into HIV care and treatment clinics in Tanzania: evaluation of a facilitated referral model.
Many clients of HIV care and treatment services have unmet contraceptive needs. Integrating family planning (FP) services into HIV services is an increasingly utilized strategy for meeting those unmet needs. However, numerous models for services integration are potentially applicable for clients with diverse health needs. This study developed and tested a 'facilitated referral' model for integrating FP into HIV care and treatment in Tanzania with the primary outcome being a reduction in unmet need for contraception among female clients. The facilitated referral model included seven distinct steps for service providers. A quasi-experimental, pre- and post-test, repeated cross-sectional study was conducted to evaluate the impact of the model. Female clients at 12 HIV care and treatment clinics (CTCs) were interviewed pre- and post-intervention and CTC providers were interviewed post-intervention. A total of 323 CTC clients were interviewed pre-intervention and 299 were interviewed post-intervention. Among all clients, the adjusted decrease in proportion with unmet need (3%) was not significant (P = 0.103) but among only sexually active clients, the adjusted decrease (8%) approached significance (P = 0.052). Furthermore, the proportion of sexually active clients using a contraceptive method post-intervention increased by an estimated 12% (P = 0.013). Dual method use increased by 16% (P = 0.004). Increases were observed for all seven steps of the model from pre- to post-intervention. All providers (n = 45) stated that FP integration was a good addition although there were implementation challenges. This study demonstrated that the facilitated referral model is a feasible strategy for integrating FP into HIV care and treatment services. The findings show that this model resulted in increased contraceptive use among HIV-positive female clients. By highlighting the distinct steps necessary for facilitated referrals, this study can help inform both programmes and future research efforts in services integration.


Draft Genome Sequences of the Nitrate-Dependent Iron-Oxidizing Proteobacteria Acidovorax sp. Strain BoFeN1 and Paracoccus pantotrophus Strain KS1.
The draft genomes of the nitrate-dependent iron-oxidizing bacteria Acidovorax sp. strain BoFeN1 and Paracoccus pantotrophus strain KS1 are presented. These genomes supply supporting data to investigations of the mechanisms underlying this anaerobic form of microbial biogeochemical iron cycling.


Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity.
The HIRA histone chaperone complex deposits histone H3.3 into nucleosomes in a DNA replication- and sequence-independent manner. As herpesvirus genomes enter the nucleus as naked DNA, we asked whether the HIRA chaperone complex affects herpesvirus infection. After infection of primary cells with HSV or CMV, or transient transfection with naked plasmid DNA, HIRA re-localizes to PML bodies, sites of cellular anti-viral activity. HIRA co-localizes with viral genomes, binds to incoming viral and plasmid DNAs and deposits histone H3.3 onto these. Anti-viral interferons (IFN) specifically induce HIRA/PML co-localization at PML nuclear bodies and HIRA recruitment to IFN target genes, although HIRA is not required for IFN-inducible expression of these genes. HIRA is, however, required for suppression of viral gene expression, virus replication and lytic infection and restricts murine CMV replication in vivo. We propose that the HIRA chaperone complex represses incoming naked viral DNAs through chromatinization as part of intrinsic cellular immunity.


Structures of Immune Checkpoints: An Overview on the CD28-B7 Family.
The co-stimulation and co-inhibition signal pathways, immune checkpoints, are among the central mechanisms to regulate the T-cell immunity. Optimal signals involve intricate interactions of numerous ligands and receptors. Manipulation of these signals offers great clinical opportunities and has revolutionized the cancer treatment therapies. The 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo in recognition of their discovery of cancer immunotherapy by inhibition of immune checkpoint molecules. Despite the landmark discovery in cancer immunotherapy, the efforts to harness immunity against cancer are also restricted by the limited knowledge on the co-stimulation and co-inhibition signaling networks. Understanding the structures of these molecules, in particular, tackling the interaction paradigms from the structural perspective, help to provide more accurate insights into the signaling mechanisms, which may further facilitate the development of novel biologics and improve the efficacy of the existing biologics against these targets. Here we review our current understanding on the structures of these co-stimulatory and co-inhibitory molecules. Specifically, we focus on the structural basis of several checkpoint molecules among the CD28-B7 family and discuss the therapeutic drugs against these targets for the treatment of human cancers, autoimmune disorders, and transplantation.


Lipemia retinalis - an unusual cause of visual acuity deterioration.
Hyperlipidemia is an identified factor of premature vessel atherosclerosis. Lipemia retinalis is an unusual retinal manifestation of hyperlipidemia and is thought to be directly correlated with the serum triglyceride level. This paper discusses the case of a 55-year-old patient with lipemia retinalis, which deteriorated his visual acuity. The patient had an extremely high serum cholesterol level (1053 mg/dl) and a very high level of triglycerides (1513 mg/dl). The normalization of serum lipids, reversion of retinal vessels alterations and visual acuity improvement was achieved after an intensive statin lipid-lowering therapy. Pathological changes of the patient's retina, connected with lipemia retinalis, disappeared completely. Hyperlipidemia can cause lipemia retinalis, which is characterized by the hyperlipidemic vascular lesions-whitish color of vessels, lipid infiltration into the retina and decrease of visual acuity. The lipid-lowering therapy may lead to the normalization of the appearance of the fundus and restore the visual acuity.


Effects of freezing on the estimated amounts of Tamm--Horsfall glycoprotein in urine, as determined by radioimmunoassay.
Freeze-drying or freezing of salt-free solutions of human Tamm--Horsfall glycoprotein appeared to lead to changes in the structure of the latter, changes that increased its ability to bind with antibody raised, in rabbits, against it. This alteration in avidity of the glycoprotein was observed irrespective of whether antiserum was raised against freeze-dried or non-frozen antigen. The implications of this finding for the radioimmunoassay of the glycoprotein in urine samples were studied. Appropriate treatment for urine samples, before assay, was devised. The amount of Tamm--Horsfall glycoprotein excreted was shown to range from 30 to 138 mg in normal males and 43 to 126 mg in normal females per 24 h.


Hyperperfusion syndrome: toward a stricter definition.
Hyperperfusion syndrome is a rare and potentially devastating complication of carotid endarterectomy or carotid artery angioplasty and stenting. With the advent of new imaging techniques, we reviewed our experience with this phenomenon. This report is a retrospective review of 129 consecutive cases of carotid endarterectomy performed between June 1, 2000, and May 31, 2002, and 44 consecutive cases of carotid artery angioplasty and stenting performed between January 1, 1997, and May 31, 2002. We specifically searched for examples of patients who developed postprocedural nonthrombotic neurological deficits that typified the hyperperfusion syndrome. Seven cases of hyperperfusion syndrome occurred, four after endarterectomy (3.1% of carotid endarterectomy cases) and three after stenting (6.8% of stenting cases). The cases of hyperperfusion were classified as presenting with 1). acute focal edema (two cases with stroke-like presentation, attributable to edema immediately after revascularization), 2). acute hemorrhage (two cases of intracerebral hemorrhage immediately after stenting and one case immediately after endarterectomy), or 3). delayed classic presentation (two cases with seizures, focal motor weakness, and/or late intracerebral hemorrhage at least 24 hours after endarterectomy). Hyperperfusion syndrome may be more common and more variable in clinical presentation than previously appreciated.


Tinnitus psychopharmacology: A comprehensive review of its pathomechanisms and management.
Subjective tinnitus is a frequent, impairing condition, which may also cause neurotransmitter imbalance at the cochlea. Psychopharmacologic agents, although not being the first-line treatment for tinnitus, may modulate cochlear neurotransmission, thereby influencing the subjective tinnitus experience. A comprehensive review of MEDLINE literature (from January 1990-January 2010) was performed searching for: "tinnitus", major classes of psychopharmacological agents, and psychiatric disorders. The most relevant clinical evidence is reported briefly along with a concise description of the main neurotransmitters purported to be involved in tinnitus, in order to provide the reader with a rational evaluation of tinnitus therapy with psychopharmacological agents. Although strong methodological issues limit the reliability of the current results, a broad number of psychopharmacological agents have already been considered for tinnitus, both as candidate triggers or potential therapies. Selected psychopharmacological drugs may play a role in the clinical management of this disorder. While the rational use of these agents for the treatment of tinnitus should not be overlooked, research should be undertaken on their neuromodulating actions at the cochlea.


Myeloid leukemia factor 1 regulates p53 by suppressing COP1 via COP9 signalosome subunit 3.
Myeloid leukemia factor 1 (MLF1) was first identified as the leukemic fusion protein NPM-MLF1 generated by the t(3;5)(q25.1;q34) chromosomal translocation. Although MLF1 expresses normally in a variety of tissues including hematopoietic stem cells and the overexpression of MLF1 correlates with malignant transformation in human cancer, little is known about how MLF1 is involved in the regulation of cell growth. Here we show that MLF1 is a negative regulator of cell cycle progression functioning upstream of the tumor suppressor p53. MLF1 induces p53-dependent cell cycle arrest in murine embryonic fibroblasts. This action requires a novel binding partner, subunit 3 of the COP9 signalosome (CSN3). A reduction in the level of CSN3 protein with small interfering RNA abrogated MLF1-induced G1 arrest and impaired the activation of p53 by genotoxic stress. Furthermore, ectopic MLF1 expression and CSN3 knockdown inversely affect the endogenous level of COP1, a ubiquitin ligase for p53. Exogenous expression of COP1 overcomes MLF1-induced growth arrest. These results indicate that MLF1 is a critical regulator of p53 and suggest its involvement in leukemogenesis through a novel CSN3-COP1 pathway.


Receptor current fluctuation analysis in the labellar sugar receptor of the fleshfly.
Fluctuations in the receptor current of the labellar sugar receptor of the fleshfly were analyzed. The receptor current was recorded extracellularly as a drop in potential between the tip and the base of the taste sensillum. After treatment with tetrodotoxin, the taste cells completely lost their impulses but retained their receptor currents, thus facilitating analysis of the receptor current without disturbance by impulses. The current fluctuation increased markedly when the sensillum was stimulated with effective sugars: maltose, sucrose, and fructose. The fluctuation increased in parallel with development of the receptor current, which indicates that it occurs as soon as the sugar reaches the apex of the sensory process. Analysis of fluctuations by computation of autocorrelation functions (ACFs) or power spectra (PS) revealed that: (a) the variance (mean square) of fluctuation vs. sugar concentration curve reached a maximum, in contrast to the monotonic increase shown by the receptor current; (b) the ACF was approximated by an exponential term, and its time constant differed according to the sugars used and their concentrations. The time constants for fructose and maltose decreased with increases in sugar concentration. At the concentrations of sugars evoking the same magnitude of receptor current, the time constant for fructose was the largest and that for maltose was the smallest. It was strongly suggested that transduction ion channels are present at the tip region of the sensory process of the sugar receptor cell and are operated directly by sugars.


A comparison of special category light-sport and corresponding type-certificated aircraft safety.
The special category light sport airplane (light sport) sector of general aviation has grown 10-fold in as many years with solo operations requiring only a sports pilot's certificate. With little research on light sport airplane safety, the study objective was to compare light sport and type-certificated airplane accident rates. Accidents were identified from the National Transportation Safety Board database. Statistics employed Poisson distribution/proportion analyses/Mann-Whitney U-tests. For the 2009-2015 period, the light sport airplane accident rate (fatal/non-fatal combined) was >15-fold higher than comparable type-certificated aircraft, undiminished over time. The excessive light sport airplane accident rate was associated with inferior airman experience (time-in-type, certification). Mishaps were most frequent during landing (40%) and, of these, nearly half were due to a deficiency in the flare. There were a dis-proportionate number of trainees involved in landing accidents compared with mishaps for other phases of operations. Towards improving safety, additional light sport training with emphasis on landings and a focus on the flare and directional control is warranted. In the confines of the present study considering that landing mishaps, the most common accident cause, are often related to deficiencies in the flare and loss-of-directional control, instructors should ensure that airmen have mastered these aspects of landing and, for trainees, acquired the appropriate visual monocular cues.


Conformationally Restricted Glycopeptide Backbone Inhibits Gas-Phase H/D Scrambling between Glycan and Peptide Moieties.
Protein glycosylation is a common post-translational modification on extracellular proteins. The conformational dynamics of several glycoproteins have been characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS). However, it is, in most cases, not possible to extract information about glycan conformation and dynamics due to the general difficulty of separating the deuterium content of the glycan from that of the peptide (in particular, for O-linked glycans). Here, we investigate whether the fragmentation of protonated glycopeptides by collision-induced dissociation (CID) can be used to determine the solution-specific deuterium content of the glycan. Central to this concept is that glycopeptides can undergo a facile loss of glycans upon CID, thereby allowing for the determination of their masses. However, an essential prerequisite is that hydrogen and deuterium (H/D) scrambling can be kept in check. Therefore, we have measured the degree of scrambling upon glycosidic bond cleavage in glycopeptides that differ in the conformational flexibility of their backbone and glycosylation pattern. Our results show that complete scrambling precedes the glycosidic bond cleavage in normal glycopeptides derived from a glycoprotein; i.e., all labile hydrogens have undergone positional randomization prior to loss of the glycan. In contrast, the glycosidic bond cleavage occurs without any scrambling in the glycopeptide antibiotic vancomycin, reflecting that the glycan cannot interact with the peptide moiety due to a conformationally restricted backbone as revealed by molecular dynamics simulations. Scrambling is also inhibited, albeit to a lesser degree, in the conformationally restricted glycopeptides ristocetin and its pseudoaglycone, demonstrating that scrambling depends on an intricate interplay between the flexibility and proximity of the glycan and the peptide backbone.


Physiotherapists' and physiotherapy students' attitudes and beliefs about working with people with dementia: a mixed methods systematic review protocol.
The objective of this review is to explore the attitudes and beliefs of physiotherapists and physiotherapy students working with people with dementia. A second objective is to explore their knowledge and confidence in this area. Dementia is a leading cause of disability. It poses a challenge to individuals and health systems due to the complex nature of its presentation. With a growing body of evidence supporting physiotherapists' role in the care of people with dementia, it is important to understand their knowledge, confidence, attitudes, and beliefs in managing this role. The review will consider quantitative, qualitative, and mixed-methods studies that include physiotherapists and physiotherapy students who have worked or had a clinical placement in any setting where people with dementia might access physiotherapy care. Studies investigating one or more of the following topics will be included: knowledge, confidence, attitudes, and beliefs about working with people with any type of dementia. MEDLINE (Ovid), CINAHL (EBSCO), Embase (Ovid), Emcare, PsycINFO (Ovid), Scopus, Web of Science, Informit, ERIC (ProQuest), ProQuest Dissertations, and Google Scholar will be searched without a date limit for studies published in English. All study types will be screened for inclusion and critically appraised for methodological quality by two independent reviewers. Methodological quality will be assessed using the appropriate JBI critical appraisal checklist for each study type. Data will be extracted using standardized JBI tools for mixed methods systematic reviews. A convergent integrated approach to synthesis and integration will be used. PROSPERO CRD42020181845.


Diagnostic windows in non-neoplastic diseases: a systematic review.
Investigating changes in prediagnostic healthcare utilisation can help identify how much earlier conditions could be diagnosed. Such 'diagnostic windows' are established for cancer but remain relatively unexplored for non-neoplastic conditions. To extract evidence on the presence and length of diagnostic windows for non-neoplastic conditions. A systematic review of studies of prediagnostic healthcare utilisation was carried out. A search strategy was developed to identify relevant studies from PubMed and Connected Papers. Data were extracted on prediagnostic healthcare use, and evidence of diagnostic window presence and length was assessed. Of 4340 studies screened, 27 were included, covering 17 non-neoplastic conditions, including both chronic (for example, Parkinson's disease) and acute conditions (for example, stroke). Prediagnostic healthcare events included primary care encounters and presentations with relevant symptoms. For 10 conditions, sufficient evidence to determine diagnostic window presence and length was available, ranging from 28 days (herpes simplex encephalitis) to 9 years (ulcerative colitis). For the remaining conditions, diagnostic windows were likely to be present, but insufficient study duration was often a barrier to robustly determining their length, meaning that diagnostic window length may exceed 10 years for coeliac disease, for example. Evidence of changing healthcare use before diagnosis exists for many non-neoplastic conditions, establishing that early diagnosis is possible, in principle. In particular, some conditions may be detectable many years earlier than they are currently diagnosed. Further research is required to accurately estimate diagnostic windows and to determine how much earlier diagnosis may be possible, and how this might be achieved.


Cytoplasmic chromatin triggers inflammation in senescence and cancer.
Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.


The Vibrio seventh pandemic island-II is a 26.9 kb genomic island present in Vibrio cholerae El Tor and O139 serogroup isolates that shows homology to a 43.4 kb genomic island in V. vulnificus.
Vibrio cholerae is the aetiological agent of the deadly diarrhoeal disease cholera. In this study the 7.5 kb Vibrio seventh pandemic island-II (VSP-II) that is unique to V. cholerae El Tor and O139 serogroups was analysed and it was found to be part of a novel 26.9 kb genomic island (GEI) encompassing VC0490-VC0516. The low-GC-content VSP-II encompassed 24 predicted ORFs, including DNA repair and methyl-accepting chemotaxis proteins, a group of hypothetical proteins and a bacteriophage-like integrase adjacent to a tRNA gene. Interestingly, V. cholerae ORFs VC0493-VC0498, VC0504-VC0510 and VC0516, which encodes an integrase, were homologous to Vibrio vulnificus strain YJ016 ORFs VV0510-VV0516, VV0518-VV0525 and VV0560, which also encodes an integrase, respectively. Some ORFs showed amino acid identities greater than 90 % between the two species in these regions. In V. vulnificus strain YJ016, a 43.4 kb low-GC-content (43 %) GEI encompassing ORFs VV0509-VV0560 was identified and named V. vulnificus island-I (VVI-I). The 52 ORFs of VVI-I included a phosphotransferase system gene cluster, genes required for sugar metabolism and transposase genes. There was synteny and homology between the 5' region of V. cholerae VSP-II and the 5' region of V. vulnificus VVI-I; however, VVI-I contained an additional 31.5 kb of DNA between VV0526 and VV0560 in strain YJ016. A second V. vulnificus strain, CMCP6, did not contain the 43.4 kb VVI-I; in this strain two ORFs were found between the 5' and 3' flanking genes VV10636 and VV10632, showing 100 % identity to VV0508 and VV0561, respectively, which flank VVI-I.


Burger or yogurt? Indulgent consumption in impression management contexts.
We conducted three studies to investigate indulgent choice in settings with and without impression management by public-private manipulation with evaluation. Study 1 showed that the participants were less indulgent under public scrutiny due to the employment of impression management. Study 2 focused on the impression management context to test the moderate effect of self-consciousness in two impression managed contexts. Study 3 focused on context without impression management to test the moderate effects of self-awareness on choices. We found that depending on differences in primed personality, individuals tended to make choices other than those they favoured privately when anticipating that others might form impressions of them based on the decisions made. The findings of all three studies support our basic prediction that people are less indulgent under impression management and suggest that people tend to manage their impression by eating healthier (less indulgently) in public.


Morning blood pressure monitoring in the management of hypertension.
: The aim of the current article is to review the current evidence on the role of morning blood pressure (BP) in the management of hypertension. Morning BP surge had been and will continue to be a hot topic of hypertension research. However, more evidence is needed to prove its clinical usefulness in the management of hypertension. Masked morning hypertension, as the other forms of masked hypertension, requires more research. The concept of morning BP monitoring could be clinically relevant in the therapeutic management of hypertension and in the prevention of cardiovascular complications by defining and treating morning hypertension. Antihypertensive medication is usually taken in the morning. The presence of uncontrolled morning BP during trough effect hours could be a hallmark of inadequate antihypertensive regimen, such as, for instance, the use of short-acting or intermediate-acting drugs, under dosing of drugs, or no or low use of combination therapy. To improve the management of hypertension in general and morning hypertension in particular, long-acting antihypertensive drugs should be used in appropriate often full dosages and in proper combinations. The clinical usefulness of antihypertensive drugs of specific mechanisms against morning BP or split or timed dosing of long-acting drugs in controlling morning BP remains under investigation. In conclusion, there is some evidence that morning BP is critical in the incidence of cardiovascular complications. However, proving its clinical usefulness in the management of hypertension requires further research.


Wearable Transmitter Coil Design for Inductive Wireless Power Transfer to Implantable Devices.
Wireless endovascular sensors and stimulators are emerging biomedical technologies for applications such as endovascular pressure monitoring, hyperthermia, and neural stimulations. Recently, coil-shaped stents have been proposed for inductive power transfer to endovascular devices using the stent as a receiver. However, less work has been done on the external transmitter components, so the maximum power transferable remains unknown. In this work, we design and evaluate a wearable transmitter coil that allows 50 mW power transfer in simulation.Clinical Relevance-This allows more accurate measurements and precise control of endovascular devices.


FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease.
Studies in animals show that fibroblast growth factor (FGF)-23 interferes with vascular reactivity induced by the nitric oxide (NO) system. To investigate the relationship between circulating FGF-23 levels and the response of forearm blood flow to ischemia (flow-mediated vasodilatation, FMD) and nitroglycerin, we tested 183 patients with stage 3-4 chronic kidney disease (CKD). None of them had cardiovascular complications or were taking drugs interfering with vascular function. Patients with FGF-23 levels above the median had significantly lower glomerular filtration rate, FMD, and fetuin-A levels (an anti-inflammatory molecule and potent inhibitor of calcification). They also had higher proteinuria and phosphate levels when compared to patients whose FGF-23 levels were below the median. The response to nitroglycerin was not different between the two groups. Multiple regression analysis showed that the relationship between FGF-23 and FMD was only modestly sensitive to adjustment for classical risk factors, biomarkers of bone mineral metabolism, high-sensitivity C-reactive protein, and homeostatic model assessment index. Adjustment for asymmetrical dimethyl arginine (ADMA) weakened the strength of this link; however, it remained highly significant. There was no independent association between FGF-23 and nitroglycerin. Thus, attenuation of FMD by ADMA suggests that this endogenous inhibitor of NO synthase may, in part, mediate the vascular effects of FGF-23 in patients with CKD.


Indirect adhesive rehabilitation by cementation under pressure of a case of Dentinogenesis Imperfecta type II: follow-up after 13 years.
Dentinogenesis imperfecta (DI) is an autosomal dominant genetic disease that affects both deciduous and permanent teeth, with an incidence of 1 out of 6,000 to 1 out of 8,000. Teeth affected with DI type II present bulbous crowns, short and constricted roots, marked cervical constriction, translucent enamel and amber dentin. Also, they present a partial or total obliteration of pulp space, due to continuous dentin production. SEM analysis has shown an undulated dentin-enamel junction (DEJ) with irregularities and locally wide spaces between the two structures instead of a strict junction and a regular linear surface. Treatment options for patients affected by DI-II are intended to protect and restore function and aesthetics of both posterior and anterior teeth. In literature are presented many different therapies, but mainly centered on cemented prosthetic restorations instead of adhesive restorative procedures. We present in this paper a DI-II case successfully treated in 2005 with extensive adhesive rehabilitation. The 13 years follow-up proves the reliability of adhesion to dentine and enamel for indirect adhesive restorations even on this kind of anomalous substrates.


Deep learning and generative methods in cheminformatics and chemical biology: navigating small molecule space intelligently.
The number of 'small' molecules that may be of interest to chemical biologists - chemical space - is enormous, but the fraction that have ever been made is tiny. Most strategies are discriminative, i.e. have involved 'forward' problems (have molecule, establish properties). However, we normally wish to solve the much harder generative or inverse problem (describe desired properties, find molecule). 'Deep' (machine) learning based on large-scale neural networks underpins technologies such as computer vision, natural language processing, driverless cars, and world-leading performance in games such as Go; it can also be applied to the solution of inverse problems in chemical biology. In particular, recent developments in deep learning admit the in silico generation of candidate molecular structures and the prediction of their properties, thereby allowing one to navigate (bio)chemical space intelligently. These methods are revolutionary but require an understanding of both (bio)chemistry and computer science to be exploited to best advantage. We give a high-level (non-mathematical) background to the deep learning revolution, and set out the crucial issue for chemical biology and informatics as a two-way mapping from the discrete nature of individual molecules to the continuous but high-dimensional latent representation that may best reflect chemical space. A variety of architectures can do this; we focus on a particular type known as variational autoencoders. We then provide some examples of recent successes of these kinds of approach, and a look towards the future.


Variation among juvenile capuchins in social influences on exploration.
The exploratory or feeding activities of others might influence the timing, the place, or both, of exploratory activities among young group-living individuals, and this influence might affect the information gained by individuals during exploration. This study examined the temporal and spatial aspects of adults' influence on the exploratory behavior of juvenile capuchins, and on the juveniles' acquisition of a novel behavior. Two experimental apparatus, which were initially novel to the juvenile subjects but familiar to the adults, and which provided food when a tool was used properly, were presented to group-housed capuchin monkeys. The apparatus were presented (a) in a central area, in which all animals could interact with the apparatus and in which several older group members regularly solved the tasks (group site), and (b) in a protected site within the home cage (crèche) that only juveniles could enter, but from which the rest of the cage, including the group site, could be viewed. Juveniles contacted the apparatus at the crèche more often when there was no apparatus at the group site, but only half the individuals made greater use of the apparatus at the group site than at the crèche when an apparatus was present at both sites. Seven of nine used an apparatus more often when adults also had an apparatus, than when adults did not have an apparatus. These results indicate that juveniles' exploratory activity is only weakly related to adults' activity. The linkage appears closer for younger juveniles (20 months or less) than for older juveniles. Moreover, as only older juveniles learned to solve the tasks, coordination of exploration with adults was evidently not related to learning a new skill. © Wiley-Liss, Inc.