Gene expression in chicken reveals correlation with structural genomic features and conserved patterns of transcription in the terrestrial vertebrates.
The chicken is an important agricultural and avian-model species. A survey of gene expression in a range of different tissues will provide a benchmark for understanding expression levels under normal physiological conditions in birds. With expression data for birds being very scant, this benchmark is of particular interest for comparative expression analysis among various terrestrial vertebrates. We carried out a gene expression survey in eight major chicken tissues using whole genome microarrays. A global picture of gene expression is presented for the eight tissues, and tissue specific as well as common gene expression were identified. A Gene Ontology (GO) term enrichment analysis showed that tissue-specific genes are enriched with GO terms reflecting the physiological functions of the specific tissue, and housekeeping genes are enriched with GO terms related to essential biological functions. Comparisons of structural genomic features between tissue-specific genes and housekeeping genes show that housekeeping genes are more compact. Specifically, coding sequence and particularly introns are shorter than genes that display more variation in expression between tissues, and in addition intergenic space was also shorter. Meanwhile, housekeeping genes are more likely to co-localize with other abundantly or highly expressed genes on the same chromosomal regions. Furthermore, comparisons of gene expression in a panel of five common tissues between birds, mammals and amphibians showed that the expression patterns across tissues are highly similar for orthologous genes compared to random gene pairs within each pair-wise comparison, indicating a high degree of functional conservation in gene expression among terrestrial vertebrates. The housekeeping genes identified in this study have shorter gene length, shorter coding sequence length, shorter introns, and shorter intergenic regions, there seems to be selection pressure on economy in genes with a wide tissue distribution, i.e. these genes are more compact. A comparative analysis showed that the expression patterns of orthologous genes are conserved in the terrestrial vertebrates during evolution.


Instability and site-specific excision of integration-proficient mycobacteriophage L5 plasmids: development of stably maintained integrative vectors.
Integrative vectors expressing foreign genes are used as tools for the development of recombinant vaccines in mycobacteria since it is assumed that these vectors are stably maintained even without antibiotic selection. We here demonstrate that integration-proficient vectors are lost from the mycobacterial genome in high frequency. Loss of integrated vectors occurred in recA+ and in recA-strains, indicating a RecA-independent mechanism. Loss of the integrated vector was prevented when integrase gene function was carried on a separate plasmid that is unable to replicate in mycobacteria, indicating that excision is a function of integrase. By providing attP in cis and integrase function in trans, vectors integrating at the attB site are stably maintained, even when carrying genes that deleteriously affect the host.


Stability analysis of a three-term backpropagation algorithm.
Efficient learning by the backpropagation (BP) algorithm is required for many practical applications. The BP algorithm calculates the weight changes of artificial neural networks, and a common approach is to use a two-term algorithm consisting of a learning rate (LR) and a momentum factor (MF). The major drawbacks of the two-term BP learning algorithm are the problems of local minima and slow convergence speeds, which limit the scope for real-time applications. Recently the addition of an extra term, called a proportional factor (PF), to the two-term BP algorithm was proposed. The third increases the speed of the BP algorithm. However, the PF term also reduces the convergence of the BP algorithm, and criteria for evaluating convergence are required to facilitate the application of the three terms BP algorithm. This paper analyzes the convergence of the new three-term backpropagation algorithm. If the learning parameters of the three-term BP algorithm satisfy the conditions given in this paper, then it is guaranteed that the system is stable and will converge to a local minimum. It is proved that if at least one of the eigenvalues of matrix F (compose of the Hessian of the cost function and the system Jacobian of the error vector at each iteration) is negative, then the system becomes unstable. Also the paper shows that all the local minima of the three-term BP algorithm cost function are stable. The relationship between the learning parameters are established in this paper such that the stability conditions are met.


Grammatical Planning Units During Real-Time Sentence Production in Speakers With Agrammatic Aphasia and Healthy Speakers.
Grammatical encoding (GE) is impaired in agrammatic aphasia; however, the nature of such deficits remains unclear. We examined grammatical planning units during real-time sentence production in speakers with agrammatic aphasia and control speakers, testing two competing models of GE. We queried whether speakers with agrammatic aphasia produce sentences word by word without advanced planning or whether hierarchical syntactic structure (i.e., verb argument structure; VAS) is encoded as part of the advanced planning unit. Experiment 1 examined production of sentences with a predefined structure (i.e., "The A and the B are above the C") using eye tracking. Experiment 2 tested production of transitive and unaccusative sentences without a predefined sentence structure in a verb-priming study. In Experiment 1, both speakers with agrammatic aphasia and young and age-matched control speakers used word-by-word strategies, selecting the first lemma (noun A) only prior to speech onset. However, in Experiment 2, unlike controls, speakers with agrammatic aphasia preplanned transitive and unaccusative sentences, encoding VAS before speech onset. Speakers with agrammatic aphasia show incremental, word-by-word production for structurally simple sentences, requiring retrieval of multiple noun lemmas. However, when sentences involve functional (thematic to grammatical) structure building, advanced planning strategies (i.e., VAS encoding) are used. This early use of hierarchical syntactic information may provide a scaffold for impaired GE in agrammatism.


Lentiviral vector-mediated dopamine d3 receptor modulation in the rat brain impairs alcohol intake and ethanol-induced conditioned place preference.
It has been reported that dopamine D3 receptor (D3R) knockout mice display similar ethanol (EtOH) consumption compared to wild types. In addition, studies with D3R pharmacological targeting were inconclusive. In the current study, we used both gain- and loss-of-function approaches to test the effects of central D3R manipulation on voluntary alcohol intake and EtOH-induced conditioned place preference (CPP) in rats. To this aim, we developed a lentiviral-mediated gene transfer approach to examine whether D3R knockdown (LV-siD3R) or overexpression (LV-D3R) in the nucleus accumbens (NAcc) is sufficient to modulate voluntary alcohol consumption and EtOH-CPP. Using the standard 2-bottle choice drinking paradigm and an unbiased CPP procedure, our results indicated that, like the D3R selective antagonist SB-277011-A, LV-siD3R attenuated voluntary alcohol consumption. In contrast, LV-D3R increased EtOH intake with no effect on total fluid intake. Similarly, the D3R agonist 7-OH-DPAT also exacerbated EtOH intake. Interestingly, neither pharmacological nor genetic manipulation of D3R activity affected saccharin and quinine consumption and preference. More importantly, we report that LV-siD3R blocked, whereas LV-D3R exacerbated, EtOH-CPP. These results support the notion that the D3R plays an important role in alcohol reward in rats and suggest that a key threshold range of D3R levels is associated with impaired alcohol consumption. Taken together, these findings demonstrate that the D3R is an essential component of the molecular pathways underlying the reinforcing properties of alcohol. Thus, medications targeting the D3Rs may be beneficial to tackle EtOH abuse and alcoholism in humans.


Pyelocalyceal cysts with hydrotic nephritis of the kidney: case of a unilateral congenital developmental anomaly.
This report describes the diagnostic, morbid, anatomical and histopathological features of pyelocalyceal cysts with hydrotic nephritis of the kidney in a 3-year-old boy, and discusses the pathogenesis. Calyceal cysts gave rise to a 'large blue cystic lobulated kidney' with microscopic changes in nephrons identifiable as 'hydrotic nephritic glomerulosclerosis'. Pelvic and calyceal cysts were identifiable by location, number, arrangement, and morbid anatomical and microscopic features of their lining walls. Such cysts may develop due to partial or complete obliterate adhesions at the uretero-pelvic and pyelocalyceal junctions. Patent calyceo-tubulonephric junctions in such cases may give rise to hydrotic nephritis. Pyelocalyceal cystic disease with hydrotic nephritis of the kidney needs to be distinguished from megacalycosis and hydronephrosis and deserves recognition. Observations in this case may provide the basis for future classifications of cystic renal diseases.


Efficacy of ultrasonography in peripheral venous cannulation.
A retrospective study of 431 patients who had peripherally inserted midclavicular or central catheters placed during a consecutive 13-month period using the conventional landmark method for placement was compared with a second group of 326 patients, who during a 12-month period had such catheters placed using ultrasonography. The data demonstrate a 42% decrease in the number of needle penetrations needed to successfully cannulate veins when ultrasound was used during placement. There is a 26% greater chance of successful cannulation of the vein on the first attempt with ultrasound-guided placements than with those using the traditional landmark method.


Studies of spatial and temporal distribution characteristics of TSP-bound trace metals in Seoul, Korea.
In the present study, TSP-bound metal concentrations were measured from seven different urbanized locations in Seoul, Korea for the period from March 2001 through May 2002. Our measurement data were analyzed to explore the possible influences of spatial and temporal factors on metal distribution characteristics. To determine the importance of those aspects, the measured concentrations were compared between different metals and between different sites in terms of several criteria: (1) absolute concentrations and enrichment factor (EF) values; (2) coefficient of variation (CV) values of metal concentrations; (3) relative patterns of temporal variations; and (4) relative abundance of strong correlations. According to our analysis of metal distribution characteristics in the study area, the main results of our study can be summarized as follows: (1) a number of metals (e.g., Cd, Cu, and Pb) are highly enriched relative to the average crustal ratios (to Fe); (2) the behavior of Cu is found to vary irregularly, while Fe, Mn, and Pb are tightly coupled both spatially and temporally in the study area; (3) for most elements except Cu and Cd, seasonal variations are observed in a systematic manner; and (4) when compared against those observed in other parts of the world, our Cu and Cd concentrations observed in many locations of Seoul are notably high. The overall results of our study suggest that the distribution characteristics of metals can be regulated strongly by spatial and temporal factors and that such controls are distinguished very clearly between different metal types.


Genetic inactivation of the adenosine A2A receptor attenuates pathologic but not developmental angiogenesis in the mouse retina.
The adenosine A(2A) receptor (A(2A)R) modulates normal vascularization and pathologic angiogenesis in many tissues and may contribute to the pathogenesis of retinopathy of prematurity (ROP) characterized by abnormal retinal vascularization in surviving premature infants. Here, the authors studied the effects of the genetic inactivation of A(2A)R on normal retinal vascularization and the development of pathologic angiogenesis in oxygen-induced retinopathy (OIR), an animal model of ROP. After exposure to 75% oxygen for 5 days (postnatal day [P] 7-P12) and subsequently to room air for the next 9 days (P13-P21), we evaluated retinal vascular morphology by ADPase staining in retinal whole mounts, retinal neovascularization response by histochemistry in serial retinal sections, and retinal VEGF gene expression by real-time PCR analysis in A(2A)R knockout (KO) mice and their wild-type (WT) littermates. At P17, A(2A)R KO mice displayed attenuated OIR compared with WT littermates, as evidenced by reduced vaso-obliteration and areas of nonperfusion in the center of the retina, reduced pathologic angiogenesis as evident by decreased non-ganglion cells and neovascular nuclei, and inhibited hypoxia-induced retinal VEGF gene expression. Notably, the attenuation of pathologic angiogenesis by A(2A)R inactivation was selective for OIR because it did not affect normal retinal vascularization during postnatal development. These findings provide the first evidence that A(2A)R is critical for the development of OIR and suggest a novel therapeutic approach of A(2A)R inactivation for ROP by selectively targeting pathologic but not developmental angiogenesis in the retina.


Connexin-Based Channel Activity Is Not Specifically Altered by Hepatocarcinogenic Chemicals.
Connexin-based channels play key roles in cellular communication and can be affected by deleterious chemicals. In this study, the effects of various genotoxic carcinogenic compounds, non-genotoxic carcinogenic compounds and non-carcinogenic compounds on the expression and functionality of connexin-based channels, both gap junctions and connexin hemichannels, were investigated in human hepatoma HepaRG cell cultures. Expression of connexin26, connexin32, and connexin43 was evaluated by means of real-time reverse transcription quantitative polymerase chain reaction analysis, immunoblot analysis and in situ immunostaining. Gap junction functionality was assessed via a scrape loading/dye transfer assay. Opening of connexin hemichannels was monitored by measuring extracellular release of adenosine triphosphate. It was found that both genotoxic and non-genotoxic carcinogenic compounds negatively affect connexin32 expression. However, no specific effects related to chemical type were observed at gap junction or connexin hemichannel functionality level.


Comparison of cinoxacin and nalidixic acid in patients with cystitis.
A single-blind comparative study was undertaken in 95 patients with cystitis. Each patient received either cinoxacin. 250 mg. qid or nalidixic acid, 1 Gm. qid for seven to fourteen days. Fifty-five patients fulfilled all the criteria for efficacy evaluations; in the cinoxacin-treated group, 26 patients (93 per cent) had a satisfactory symptomatic response, and in the nalidixic acid group there were 25 patients (93 per cent) with a satisfactory symptomatic response. The bacteriologic response was also similar in both groups. One patient in each group became reinfected with a new pathogen and in 1 patient, who received conoxacin, the causative pathogen was not eliminated. four female patients in the cinoxacin group had seven adverse drug reactions, compared with 9 patients in the nalidixic acid group who had 18 adverse reactions. It is concluded that cinoxacin has advantages over nalidixic acid for the treatment of patients with cystitis due to susceptible organisms.


Quantitative analysis of current trends in the development of biology of aging: scientometric and expert values.
Modern trends in the development of biology of aging have been assessed quantitatively by means of the scientometric and collective expert values methods as a part of the science-of-science analysis. The main regularities in the development of biology of aging during the period 1975 to 1985 are established and their comparative significance determined. The proposed complex approach as part of a science-of-science analysis allows an objective quantitation of the development dynamics of present basic research in gerontology.


Mechanical Property of Polypropylene Gels Associated with That of Molten Polypropylenes.
This study aims to understand the fundamental mechanical relationship between polypropylene (PP)-gels and solid PPs without solvent through mechanical and thermal analyses, by which the mechanical similarities between molten PPs and PP gels were found, leading to the reliable estimate of the mechanical properties of semi-crystalline gels. The gelation of syndiotactic and isotactic polypropylenes (sPP and iPP) was found when PPs were dissolved in 1,2,3,4-tetrahydronaphthalene (tetralin). Interestingly, it was found that the storage modulus of sPP-gel became higher than that of iPP-gel at low PP concentration (<~40 wt%). The result was distinctly different from the result of neat solid PPs (without solvent), where the modulus of solid sPP is generally significantly lower than that of solid iPP. Such inversion behavior in the mechanical property of semi-crystalline gels had not been reported and discussed before. By further investigation of the storage moduli of neat sPP and iPP, it was found that the storage modulus of sPP became higher than that of iPP above the melting points of PP, which was similar to the behavior of the storage moduli observed in the diluted PP-gels. Such similarity between PP-gels and PP melts was also observed within iPP samples with different molecular weights.


Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer.
Pancreatic cancer is one of the most incurable and lethal human cancers in the United States. To facilitate development of novel therapeutic agents, we previously established an orthotopic pancreatic tumor model that closely mimics the natural biological behavior of human pancreatic cancer. In this study, magnetic resonance imaging (MRI) techniques were developed to detect tumor formation noninvasively and monitor serially tumor growth kinetics in this orthotopic model used for experimental drug testing. By using an optimized T2-weighted imaging method, we were able to distinguish human pancreas cancer from normal mouse pancreas. Orthotopic tumor formation was detected as early as day 1 after tumor cell implantation with a tumor volume as small as 12 mm3. Mice with evidence of tumor were separated into four treatment groups: control, auristatin-PE, gemcitabine, and their combination. After treatment, the mice were imaged at least three times before termination of the experiment. Comparison between MRI tumor volume measurements and tumor weights made at biopsy resulted in a correlation coefficient of 0.98. The tumor growth curves constructed from serial magnetic resonance imaging (MRI) measurements clearly showed tumor growth inhibition in treated mice compared with the control group. As expected, the group treated with the combination had the highest response rate compared with either auristatin-PE or gemcitabine alone, and the data were statistically highly significant (p < 0.004). From these results, we conclude that noninvasive MRI can be used to monitor serially therapeutic response in this orthotopic human pancreatic tumor model and can be used in the future to evaluate novel antitumor agents before human studies.


[Prediction of the time of development and survival of ascarid eggs in the soil in the Kursk Region].
The paper shows that the currently available methods used to predict the time of development and survival of ascarid eggs in the soil, by analyzing its temperature and moisture (bioclimatograms and nomograms), provide no precise information. At the same time soil chemical and man-made pollution by heavy metals and the presence of geomagnetic fields are disregarded. Improved bioclimatographic and nomographic methods are proposed, with the correction factors being kept in mind.


Argon microwave plasma treatment and subsequent hydrosilylation grafting as a way to obtain silicone biomaterials with well-defined surface structures.
A method of grafting well-defined and hydrolytically stable surface structures onto cross-linked poly(dimethylsiloxane) (PDMS) has been developed. In the first step, argon microwave plasma was used to introduce Si-H groups onto the surface. In the second step, allyltetrafluoroethyl ether was grafted to these Si-H groups using a platinum-catalyzed hydrosilylation reaction. The influences of the plasma parameters of power, pressure, and treatment time on the surface composition, both before and after the hydrosilylation step, were investigated by X-ray photoelectron spectroscopy and contact angle measurements. It was found that the pressure had little influence on the results, whereas the power and treatment time determined the rate of change in surface composition during the plasma treatment. The graft yield reached a plateau value corresponding to about 5% grafted molecules in the analyzed surface region. Hydrosilylation grafting of PDMS is a promising method to obtain biomaterials with hydrolytically stable structures covalently bound to the surface.


The Psychological Distress of Cancer Patients following the COVID-19 Pandemic First Lockdown: Results from a Large French Survey.
Cancer patients commonly experience psychological distress that may increase with the current COVID-19 pandemic. This prospective study aimed to measure post-traumatic stress disorder (PTSD) and anxiety in cancer patients following France's first COVID-19-related lockdown, together with associated factors. Cancer patients receiving outpatient treatment or post-treatment follow-up completed a questionnaire which measured, among other things, PTSD (IES-R), anxiety (State-Trait Anxiety Inventory), and fear of cancer recurrence (FCR). Of the 1097 patients included in the study, 14.7% and 30.5% suffered from PTSD and anxiety, respectively. Patients afraid to come to hospital due to the risk of COVID-19 transmission (OR = 3.49, p < 0.001), those with a negative lockdown experience (OR = 0.98, p < 0.001), women (OR = 1.97; p = 0.009), and patients living alone (OR = 1.63, p = 0.045) were all more likely to have PTSD. Older patients (OR = 1.65, p = 0.020), women (OR = 1.62, p = 0.018), those with a higher FCR score (OR = 5.02, p < 0.001), patients unsatisfied with their cancer management (OR = 2.36, p < 0.001), and those afraid to come to hospital due to COVID-19 (OR = 2.43, p < 0.001) all had a higher risk of anxiety. These results provide a greater understanding of the psychological consequences of the COVID-19 pandemic in cancer patients and highlight the need to better integrate psychosocial support in pandemic response measures in order to guide health systems.


Antibody responses against Porphyromonas gingivalis infection in patients with early-onset periodontitis.
The aim of this study was to evaluate antibody responses against Porphyromonas gingivalis (P. gingivalis) infection in early-onset periodontitis (EOP) patients to elucidate further the host-parasite interactions in the pathogenesis of EOP. 16 P. gingivalis-infected EOP and 20 adult periodontitis (AP) patients, and 18 periodontally healthy subjects (HS) participated in this study. Serum immunoglobulin G (IgG) antibody levels and avidities against extracted P. gingivalis whole cells were measured. The components of P. gingivalis outer membrane antigens (OMA) reacting to patients' sera were analysed from the molecular weights by Western blotting. Serum antibody levels against P. gingivalis lipopolysaccharide (LPS) were also measured. The ability of the patients' sera to block interleukin-1beta (IL-1beta) production by human mononuclear cells in response to P. gingivalis LPS was examined. Antibody levels were positively correlated with antibody avidities in both EOP and AP patients (r=0.91, r=0.72, p<0.0005, respectively), while not significantly so in HS (r=0.09). There was variability in the antigen recognition of P. gingivalis OMA in EOP and AP patients. Smear and 53-kDa protein were more frequently recognized by sera of EOP and AP patients rather than that of HS (p<0.05). The smear was partly diminished by absorption with P. gingivalis LPS, indicating the smear antigen was partly composed of LPS. There was high correlation between antibody levels against P. gingivalis whole-cell extracts and LPS in EOP and AP patients (r=0.81, p=0.0002, r=0.87, p<0.0001, respectively), while not significant in HS (r=0.22). The sera of EOP and AP patients with high IgG titre to P. gingivalis LPS blocked IL-1beta production more effectively than that of the patients with low IgG titre to P. gingivalis LPS. These results indicate that EOP patients' antibody response against P. gingivalis infection does not differ significantly from that of AP patients. The person-to-person heterogeneous antibody production against P. gingivalis LPS could contribute to our understanding of the relationship between the defensive ability of EOP patients and their chronic infection with this pathogen.


Low-energy endocardial defibrillation using an axillary or a pectoral thoracic electrode location.
A significant proportion of patients receiving endocardial defibrillation lead systems must accept either high defibrillation thresholds (DFTs) with lower safety margins or lead implantation by thoracotomy. We examined the feasibility of achieving universal application of endocardial leads and lower defibrillation energy requirements by optimizing the lead system location in conjunction with biphasic shocks. Two defibrillation catheter electrodes were positioned in the right ventricle and superior vena cava. Thoracic patch electrodes were placed at three sites (apical, pectoral, and axillary). Fifteen-joule, 10-J, and 5-J bidirectional simultaneous biphasic shocks were delivered across three different triple electrode configurations (right ventricle, superior vena cava, and patch) after inducing ventricular fibrillation (VF), and DFT was determined. All patients in whom VF was reproducibly inducible (14 patients) could be reproducibly defibrillated at 15 J at one or more patch electrode locations. Fifteen-joule shocks were effective at three thoracic electrode locations in 12 patients and at two electrode locations in 6 patients. The lowest mean single-shock DFT was 8.1 +/- 3.8 J. In 4 patients, ventricular flutter was reproducibly induced and reverted at 15 J in all patients. Mean DFT for the axillary location was 8.3 +/- 3.5 J and was significantly lower than apical (12.8 +/- 5.6 J, P = .008) and pectoral (11.6 +/- 4.1 J, P < .04) patch locations. The probability of success was significantly higher at 10 J with axillary location (78% of patients, P < .03 compared with both other sites) and at 15 J (P < .05 compared with the apical location). Low-energy endocardial defibrillation (< or = 10 J) was feasible in 10 of 14 tested patients at more than 1 thoracic electrode location at 10 J, whereas only 1 of 7 successful patients could be reverted at more than 1 electrode location at 5 J (P < .02). The use of axillary or pectoral patch lead location can allow endocardial defibrillation with biphasic shocks at energies < or = 15 J in this lead configuration. Virtually universal application of endocardial defibrillation lead systems can be predicted from these data. Reduction in maximum pulse generator output to < or = 25 J using these two thoracic electrode locations with bidirectional shocks can be feasible and maintain an adequate safety margin and permit thoracic pulse generator implantation. Lowering endocardial defibrillation energy < 10 J requires increasing specificity of thoracic electrode location.


Tunable nanomechanical performance regimes in ceramic nanowires.
At the macroscopic size regime, ceramic materials exhibit brittle fracture and catastrophic failure when they are subjected to mechanical loads that exceed their characteristic strength. In this report, we present recoverable plasticity in alpha-phase, potassium stabilized manganese dioxide nanowire (α-K0.13MnO2 NW) crystals when they are subjected to atomic force microscopy (AFM) based three-point bending tests at very low loading rates. The force-deflection curves and AFM scans obtained from these measurements reveal yielding and extended plasticity in the NWs during the loading process, while the large plastic deformation is recovered spontaneously during the unloading process. However, the same material system exhibits failure via fracture at substantially higher strengths when it is subjected to bending tests at nearly an order of magnitude higher loading rates. These results highlight an important new pathway to controllably tune the nanomechanical performance of these technologically important nanoceramics for application-specific needs: either achieve self-reversible and ultra-large plasticity, or achieve substantially higher fracture strengths that approach the intrinsic limits of the material system.


Cellular markers of muscle atrophy in chronic obstructive pulmonary disease.
Skeletal muscle atrophy in individuals with advanced chronic obstructive pulmonary disease (COPD) is associated with diminished quality of life, increased health resource use, and worsened survival. Muscle wasting results from an imbalance between protein degradation and synthesis, and is enhanced by decreased regenerative repair. We investigated the activation of cellular signaling networks known to mediate muscle atrophy and regulate muscle regenerative capacity in rodent models, in individuals with COPD (FEV(1) < 50% predicted). Nine patients with COPD and nine control individuals were studied. Quadriceps femoris muscle isometric contractile force and cross-sectional area were confirmed to be significantly smaller in the patients with COPD compared with control subjects. The vastus lateralis muscle was biopsied and muscle transcript and/or protein levels of key components of ubiquitin-mediated proteolytic systems (MuRF1, atrogin-1, Nedd4), inflammatory mediators (IkappaBalpha, NF-kappaBp65/p50), AKT network (AKT, GSK3beta, p70S6 kinase), mediators of autophagy (beclin-1, LC3), and myogenesis (myogenin, MyoD, Myf5, myostatin) were determined. Atrogin-1 and Nedd4, two ligases regulating ubiquitin-mediated protein degradation and myostatin, a negative regulator of muscle growth, were significantly increased in the muscle of patients with COPD. MuRF1, Myf5, myogenin, and MyoD were not differentially expressed. There were no differences in the level of phosphorylation of AKT, GSK3beta, p70S6kinase, or IkappaBalpha, activation of NF-kappaBp65 or NF-kappaBp50, or level of expression of beclin-1 or LC3, suggesting that AKT signaling was not down-regulated and the NF-kappaB inflammatory pathway and autophagy were not activated in the COPD muscle. We conclude that muscle atrophy associated with COPD results from the recruitment of specific regulators of ubiquitin-mediated proteolytic pathways and inhibition of muscle growth.


Deprivation matters: understanding associations between neighbourhood deprivation, unhealthy food outlets, unhealthy dietary behaviours and child body size using structural equation modelling.
Children residing in neighbourhoods of high deprivation are more likely to have poorer health, including excess body size. While the availability of unhealthy food outlets are increasingly considered important for excess child body size, less is known about how neighbourhood deprivation, unhealthy food outlets and unhealthy dietary behaviours are interlinked. This study involves children aged 8-13 years (n=1029) and resided in Auckland, New Zealand. Unhealthy dietary behaviours (frequency of consumption of unhealthy snacks and drinks) and food purchasing behaviour on the route to and from school were self-reported. Height and waist circumference were measured to calculate waist-to-height ratio (WtHR). Geographic Information Systems mapped neighbourhood deprivation and unhealthy food outlets within individual, child-specific neighbourhood buffer boundaries (800 m around the home and school). Associations between neighbourhood deprivation (calculated using the New Zealand Index of Deprivation 2013), unhealthy food outlets, unhealthy dietary behaviours and WtHR were investigated using structural equation modelling in Mplus V.8.0. Age, sex and ethnicity were included as covariates, and clustering was accounted for at the school level. Structural equation models showed that unhealthy food outlets were unrelated to unhealthy dietary behaviours (estimate 0.029, p=0.416) and excess body size (estimate -0.038, p=0.400). However, greater neighbourhood deprivation and poorer dietary behaviours (estimate -0.134, p=0.001) were associated with greater WtHR (estimate 0.169, p<0.001). Excess child body size is associated with neighbourhood deprivation and unhealthy dietary behaviours but not unhealthy outlet density or location of these outlets near home and school.


Fatal severe vasospasm due to rewarming following hypothermia--case report.
A 37-year-old female died of cerebral vasospasm as a complication of rewarming following hypothermia therapy for severe head injury. She presented with severe consciousness disturbance and anisocoria after falling down a flight of stairs. Computed tomography (CT) revealed a right acute subdural hematoma and temporal contusion. Following surgery, mild hypothermia was started and rewarming was completed by the 11th day. Neurological examination showed no abnormalities, but intracranial pressure (ICP) suddenly increased and she manifested anisocoria on the 13th day. Repeat CT revealed a low density area in the right middle cerebral artery region and cerebral angiography showed diffuse narrowing of the main arterial trunks. A cerebrospinal fluid (CSF) sample was collected using an intraventricular ICP monitoring catheter. The CSF level of 8-hydroxy-2'-deoxyguanosine was elevated during the rewarming period, indicating substantial deoxyribonucleic acid (DNA) oxidation. She died on the 15th day due to uncontrollable ICP. Histological examination at autopsy of the narrowed artery found the waving phenomenon in the internal elastic lamina and invasion of inflammatory cells into the adventitia. These findings constitute the possible evidence that free-radical-mediated oxidative DNA damage may be important in the genesis of severe vasospasm due to rewarming following hypothermia.


Impact of nasal continuous positive airway pressure treatment on quality of life in patients with obstructive sleep apnoea.
Quality-of-life (QoL) issues have become increasingly important in health care practice and research. Obstructive sleep apnoea syndrome (OSAS) results in an especially serious reduction in QoL. The purpose of this study was to measure the QoL (life satisfaction) of OSAS patients treated with nasal continuous positive airway pressure (nCPAP). We aimed to determine whether and to what extent the QoL of OSAS patients using nCPAP differs from that of randomly selected subjects without this disorder. The QoL of 67 patients treated for at least 3 months with nCPAP, 21 OSAS patients at the time of OSAS diagnosis, and 113 randomly selected persons visiting the hospital (controls) was investigated with the help of the Munich life-quality dimension list (MLDL), an instrument for cognitive assessment of elementary components (physical condition, psyche, social life, everyday life) of QoL. It was found that QoL of OSAS patients treated with nCPAP did not significantly differ from that of control subjects with regard to elementary components. The 21 untreated OSAS patients showed significantly lower scores in all four subcategories: physical condition (p<0.0005), psyche (p<0.01), social life (p<0.0005) and everyday life (p<0.007). Thus, it may be concluded that nasal continuous positive airway pressure therapy has an important impact on the quality of life of obstructive sleep apnoea syndrome patients, and signifies a further advantage in addition to clinical aspects. Treated patients are as satisfied or dissatisfied with their life as persons without this illness.


Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high-fat diet.
Consuming a high-fat diet (HFD) may result in behavioral deficits similar to those observed in aging animals. Blueberries may prevent and even reverse age-related alterations in neurochemistry and behavior. It was previously demonstrated that middle-aged mice fed HFD had impaired memory; however, supplementation of HFD with blueberry reduced these memory deficits. As a follow-up to that study, the brain tissue from HFD-fed mice with and without blueberry supplementation was assessed to determine the neuroprotective mechanism(s) by which blueberry allayed cognitive dysfunction associated with HFD. Mice were fed HFDs (60% calories from fat) or low-fat diets (LFD) with and without 4% blueberry (freeze-dried, U.S. Highbush Blueberry Council). Microglia activation was assessed ex vivo and in vitro. The hippocampus was assessed for brain-derived neurotrophic factor (BDNF) and neurogenesis by measuring doublecortin (DCX). There was significantly less microglia ionized calcium binding adaptor molecule 1 staining and fewer microglia in the brains of mice fed HFD + blueberry compared to mice fed LFD and HFD. BV-2 microglial cells treated with serum collected from the mice fed the diets supplemented with blueberry produced less nitric oxide compared to cells treated with serum from mice fed HFD. BDNF levels were higher and the number of DCX-positive cells was greater in the hippocampus of mice fed HFD + blueberry compared to mice fed HFD. This study demonstrated that supplementation of a HFD with blueberry reduced indices of microglia activation and increased neuroplasticity, and these changes may underlie the protection against memory deficits in HFD-fed mice supplemented with blueberry.


Anesthetic drugs and bariatric surgery.
The prevalence of obesity is increasing worldwide. For severely obese patients, bariatric surgery is the only effective option for sustained weight loss and associated health improvement. As a consequence, the number of bariatric surgical procedures being performed is growing exponentially. Systematic knowledge regarding the effect of obesity on the pharmacokinetics and pharmacodynamics of anesthetic agents is generally lacking, and data for morbidly obese (body mass index [BMI] 40-49 kg/m2)) and super-obese patients (BMI > 50 kg/m2) are almost completely non-existent. Most drug-dosing guidelines are based on results from relatively small studies in moderately obese patients. Future systematic pharmacological research is needed for improved and more rational peri-operative care of morbidly obese patients.


Surveillance of Escherichia coli in different types of chicken and duck hatcheries: one health outlook.
Escherichia coli is an important zoonotic bacterium that significantly impacts one health concept. E. coli is normally detected in the gut of warm-blooded animals, but some serotypes can cause diseases in humans and animals. Moreover, it can continue for a long time in different environments, replicate in water, and survive outside different hosts. In this study, 171 samples collected from 10 different types of poultry hatcheries (automatic, semiautomatic, and manual "traditional" types) were examined for the prevalence of E. coli. PCR was applied to verify the E. coli isolates via 16S rRNA gene-specific primers. From the gathered samples, 62 E. coli isolates were recovered (36.3%). The highest prevalence was met with the manual "traditional" hatcheries (57.1%) with no significance difference (P = 0.243) in the 3 types of hatcheries. The incidence of E. coli varied significantly in different tested avian types and breeds. The prevalence was 35.7% in duck hatcheries and 37% in chicken hatcheries, with significant differences between breeds of both species (P = 0.024 and 0.001, respectively). The identification of zoonotic E. coli serotypes in this study is concerning, highlighting the need for collaborative efforts across various sectors, including social, environmental, and governance, to promote the adoption of the one health principle in the chicken business. Periodical surveillance, biosecurity measures at the hatcheries and farm levels, and boosting the immunity of birds were recommended to limit the risk of E. coli spread from avian sources to humans.


Structure and function of renal macrophages and dendritic cells from lupus-prone mice.
To characterize renal macrophages and dendritic cells (DCs) in 2 murine models of lupus nephritis. We used a bead-based enrichment step followed by cell sorting to isolate populations of interest from young mice and nephritic mice. Cell morphology was examined by microscopy. Arginase and nitrite production was examined using biochemical assays. The antigen-presenting functions of the cells were determined using mixed lymphocyte reactions. Selected cytokine, chemokine, and Toll-like receptor (TLR) profiles were examined using real-time quantitative polymerase chain reaction. We identified 2 populations of macrophages and 3 populations of DCs in both of our murine models of lupus (NZB/NZW and [NZW × BXSB]F1 mice). F4/80(high) macrophages, which were resident in normal kidneys and found to be increased in number during nephritis, did not produce either arginase or nitrite upon cytokine stimulation and acquired a mixed proinflammatory and antiinflammatory functional phenotype during nephritis that resembles the constitutively activated phenotype of gut F4/80(high) macrophages. The various cell types differed in their expression of chemokine receptors and TLRs, consistent with variability in their renal location. Resident renal CD103+ DCs were the best antigen-presenting cells and could easily be distinguished from CD11c(high) myeloid DCs that accumulated in large numbers during nephritis. Our study highlights the heterogeneity of the macrophage/DC infiltrate in chronic lupus nephritis and provides an initial phenotypic and functional analysis of the different cellular components that can now be used to define the role of each cell subset in nephritis progression or amelioration. Of note, the dominant macrophage population that accumulates during nephritis has an acquired phenotype that is neither M1 nor M2 and may reflect failure of resolution of inflammation.


Mouse prostate proteomes are differentially altered by supranutritional intake of four selenium compounds.
We have shown that, in contrast to selenomethionine (SeMet) or selenite, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) exert prostate cancer (PCa) inhibitory effect in preclinical models. Here we investigated the prostate proteome signatures of mice treated with each selenium (Se) form for hypothesis generation concerning their potential in vivo molecular targets and cancer risk modification. Nude mice bearing subcutaneous PC-3 xenografts were treated daily with each Se form (3 mg Se/kg) orally for 45 days. Five prostates were pooled from each group. Their proteomes were profiled by LC-MS/MS with iTRAQ labeling. Of the 1,088 proteins identified, 72 were significantly modulated by one or more Se forms. MSeA and MSeC each induced separate sets of tumor suppressor proteins and suppressed different onco-proteins. Proteins induced by selenite and shared with MSeC were related to energy metabolism (e.g., fatty-acid synthase), and those induced by SeMet included vimentin and heat-shock protein-70, favoring cancer growth. While proteome changes induced by MSeA were associated with PCa risk reduction, desirable risk-reducing signatures induced by MSeC were counterbalanced by risk-promoting patterns shared with selenite and SeMet. We propose that the balance of oncogenic vs. suppressor protein patterns in the prostate may impact the direction of PCa risk modification by a given selenium.


The interval ejection fraction: a cineangiographic and radionuclide study.
To evaluate the clinical usefulness of the first-third ejection fraction (1/3 EF) for detecting patients with coronary artery disease (CAD), resting contrast ventriculography and first-pass radionuclide angiography with a high-count-rate, multicrystal camera system were performed in 47 subjects: 22 normal controls (group 1) and 25 patients with clinically stable angina pectoris and severe CAD (mean 2.3 vessels) without (group 2, n = 12) and with (group 3, n = 13) resting wall motion abnormalities. By contrast angiography, only group 3 had depressed global EF or 1/3 EF compared with control (global EF: group 1,0.71 +/- 0.09; group 2, 0.67 +/- 0.09 [NS]; group 3,049 +/- 0.05 [p less than 0.01 vs groups 1 and 2]; 1/3 EF: group 1,0.29% +/- 0.06;' group 2, 0.28 +/- 0.05 [NS]; group 3,0.22 +/- 0.05 [p less than 0.02 vs groups 1 and 2]). Whereas 11 of 25 CAD patients had global EF outside the normal range, only two of 25 had depressed 1/3 EF. Both had left ventricular asynergy and a depressed global EF. Studies performed using first-pass radionuclide angiography revealed similar results i.e., only four of 25 CAD patients, all with left ventricular asynergy and depressed global EF, had depressed 1/3 EF values. A wide range of 1/3 EF values was found in normal subjects by both techniques. Thus, the ejection fraction during the first third of systole at rest is of limited value for detecting patients with CAD.


Creation of an Anti-Inflammatory, Leptin-Dependent Anti-Obesity Celastrol Mimic with Better Druggability.
Obesity is characterized by an excessive body mass, but is also closely associated with metabolic syndrome. And, so far, only limited pharmacological treatments are available for obesity management. Celastrol, a pentacyclic triterpenoid from a traditional Chinese medicine (Tripterygium wilfordii Hook.f.), has shown remarkable potency against obesity, inflammation and cancer, but its high toxicity, low natural abundance and tedious chemical synthesis hindered its translation into clinics. In the present work, a triterpenoid library was screened for compounds with both high natural abundance and structural similarity to celastrol; from this library, glycyrrhetinic acid (GA), a compound present in extremely high yields in Glycyrrhiza uralensis Fisch. ex DC., was selected as a possible scaffold for a celastrol mimic active against obesity. A simple chemical modification of GA resulted in GA-02, a derivative that suppressed 68% of food intake in diet-induced obesity mice and led to 26.4% weight loss in 2 weeks. GA-02 plays a role in obesity treatment by re-activating leptin signaling and reducing systemic and, more importantly, hypothalamic inflammation. GA-02 was readily bioavailable with unnoticeable in vitro and in vivo toxicities. The strategy of scaffold search and modification on the basis of bio-content and structural similarity has proved to be a green, economic, efficient and practical way of widening the medicinal applications of "imperfect" bioactive natural compounds.


[Diagnosis of and surgical therapy for pheochromocytoma and paraganglioma].
Pheochromocytomas and paragangliomas are rare chromaffin tumours that represent an exceptional challenge for the surgeon because of the concomitant secretion of catecholamines. Recent findings on the genetic background of hereditary tumours have challenged the rule of the 10 % -tumour and significantly changed the requirements for preoperative work-up and surgical strategy. Early detection of malignant growth or multiple hereditary tumours is the goal of imaging techniques such as CT/MRI, (123)I-MIBG-(SPECT) or (18)F-DOPA-PET. However, in the absence of metastasis, reliable differentiation between -benign and malignant growth is preoperatively and even histopathologically rarely possible. An essential precondition for successful surgical therapy with low operative risks is an adequate pretreatment with alpha-adrenergic antagonists which should slowly be increased to 3-5 mg/kg BW/day prior to resection. Dopamine-secreting paragangliomas represent the sole exception. Minimally invasive techniques using a transabdominal or retroperitoneal approach have become the gold standard for the resection of unifocal benign pheochromocytomas. In addition, most paragangliomas located below the diaphragm can be resected with a minimally invasive approach which, however, demands exceptional expertise. Open transabdominal resections are an approved therapy for large or potentially -malignant tumours and for settings with multi-focal tumour sites. Even for advanced malignant tumours, surgical debulking may be reasonable to improve the patient's quality of life and prognosis.


Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy.
Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid's role in fetal brain development. To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy. In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019. Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines. Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-μg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 μm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-μg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 μg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study. The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring.


Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension.
The effects of different types of adrenoreceptor blocking agents on portal venous pressure were studied in patients with cirrhosis and portal hypertension. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta 1 and beta 2 blocker), and prazosin (alpha blocker) were compared in three groups of eight patients. Haemodynamic measurements were made before and after two or three and eight weeks of therapy. The dose of beta blockers was sufficient to reduce the exercise heart rate by more than 25%. Propranolol and prazosin produced a sustained reduction in the mean portohepatic venous pressure gradient of the order of 25% and 18% respectively. The cardiac index was significantly reduced by propranolol but not altered by prazosin. Atenolol produced an early reduction in portohepatic venous pressure which, although not sustained, showed a good correlation with reduction in cardiac index. No such relationship was found with propranolol. All three drugs were well tolerated by these patients with advanced cirrhosis. Therefore propranolol and prazosin have proved to be effective agents for the reduction of portal venous pressure.


Longitudinal Poisson regression to evaluate the epidemiology of Cryptosporidium, Giardia, and fecal indicator bacteria in coastal California wetlands.
Fecal pathogen contamination of watersheds worldwide is increasingly recognized, and natural wetlands may have an important role in mitigating fecal pathogen pollution flowing downstream. Given that waterborne protozoa, such as Cryptosporidium and Giardia, are transported within surface waters, this study evaluated associations between fecal protozoa and various wetland-specific and environmental risk factors. This study focused on three distinct coastal California wetlands: (i) a tidally influenced slough bordered by urban and agricultural areas, (ii) a seasonal wetland adjacent to a dairy, and (iii) a constructed wetland that receives agricultural runoff. Wetland type, seasonality, rainfall, and various water quality parameters were evaluated using longitudinal Poisson regression to model effects on concentrations of protozoa and indicator bacteria (Escherichia coli and total coliform). Among wetland types, the dairy wetland exhibited the highest protozoal and bacterial concentrations, and despite significant reductions in microbe concentrations, the wetland could still be seen to influence water quality in the downstream tidal wetland. Additionally, recent rainfall events were associated with higher protozoal and bacterial counts in wetland water samples across all wetland types. Notably, detection of E. coli concentrations greater than a 400 most probable number (MPN) per 100 ml was associated with higher Cryptosporidium oocyst and Giardia cyst concentrations. These findings show that natural wetlands draining agricultural and livestock operation runoff into human-utilized waterways should be considered potential sources of pathogens and that wetlands can be instrumental in reducing pathogen loads to downstream waters.


Endothelial permeability and VE-cadherin: a wacky comradeship.
The endothelium forms a selective semi-permeable barrier controlling bidirectional transfer between blood vessel and irrigated tissues. This crucial function relies on the dynamic architecture of endothelial cell-cell junctions, and in particular, VE-cadherin-mediated contacts. VE-cadherin indeed chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes. In this review, the way VE-cadherin-based contacts are formed and maintained is first presented, including molecular traits of its expression, partners, and signaling. In a second part, the mechanisms by which VE-cadherin adhesion can be disrupted, leading to cell-cell junction weakening and endothelial permeability increase, are described. Overall, the molecular basis for VE-cadherin control of the endothelial barrier function is of high interest for biomedical research, as vascular leakage is observed in many pathological conditions and human diseases.


The content of hope in ambulatory patients with colon cancer.
Although hope is a pervasive concept in cancer treatment, we know little about how ambulatory patients with cancer define or experience hope. We explored hope through semistructured interviews with ten patients with advanced (some curable, some incurable) colon cancer at one Midwestern, university-based cancer center. We conducted a thematic analysis to identify key concepts related to patient perceptions of hope. Although we did ask specifically about hope, patients also often revealed their hopes in response to indirect questions or by telling stories about their cancer experience. We identified four major themes related to hope: 1) hope is essential, 2) a change in perspective, 3) the content of hope, and 4) communicating about hope. The third theme, the content of hope, included three subthemes: a) the desire for normalcy, b) future plans, and c) hope for a cure. We conclude that hope is an essential concept for patients undergoing treatment for cancer as it pertains to their psychological well-being and quality of life, and hope for a cure is not and should not be the only consideration. In a clinical context, the exploration of patients' hopes and aspirations in light of their cancer diagnosis is important because it provides a frame for understanding their goals for treatment. Exploration of the content of patients' hope can not only help to illuminate misunderstandings but also clarify how potential treatments may or may not contribute to achieving patients' goals.


Overview of the conference and the field.
The field of neuroimmune interactions is a prime example of interdisciplinary research spanning immunology, neurobiology, neuroendocrinology, and behavioral sciences. It also exemplifies research from the molecular to the clinical domain. The greatest challenge of the field, which this conference seeks to stimulate, is research that is at the same time precise, focused, and integrative. Several levels of interdisciplinary overlap will be highlighted. At the molecular level, neuro- and immune mediator molecules or their receptors may be members of the same superfamily or may regulate each other's expression or function. Most extensively studied are cytokine-neuropeptide/neurotransmitter interactions, including expression of cytokines within the central nervous system and production of neuropeptides by immune cells or at inflammatory sites. Advances relating cytokine-neurohormone interactions to mechanisms of apoptosis will ultimately shed light on the role of neuroimmune interactions in neuronal cell death and survival and immune cell selection, processes important in neuronal plasticity and immune specificity. At a systems level, advances have been made in cross-disciplinary application of modes of thinking. Incorporation of neurobiology's appreciation of anatomical organization, endocrinology's temporal dimension of neurohormonal secretion, and immunology's understanding of stimulus specificity all contribute to a more precise definition of how these complex systems interact at multiple levels. More precise understanding of effects of disruptions of these communications on disease susceptibility and expression will clarify how perturbations of one system, such as stimulation of the neuroendocrine stress response, might affect expression of disease in the other, such as autoimmune/inflammatory or infectious diseases.


[The treatment of ptyalism in children with cerebral lesions (author's transl)].
The cytotoxic and alkylating substance, mustard gas, causes both acute poisoning and also damage to numerous organs following chronic exposure. Especially important is the carcinogenic effect, also confirmed in humans. 34 years after occupational exposure to mustard gas with many intoxication episodes, a former munition-worker died of a glioblastoma; two years before his death a neurofibroma was detected in the thorax and removed by operation. The causal connection between the mustard gas exposure and the development of two neurogenic tumors rests on the statistically significantly raised frequency of malignant tumors and the established psychic changes in former workers with mustard gas and especially on the production of malignant tumors of the central nervous system in experimental animals with alkylating nitrosamines.


Survey of ultrasound practice amongst podiatrists in the UK.
Ultrasound in podiatry practice encompasses musculoskeletal ultrasound imaging, vascular hand-held Doppler ultrasound and therapeutic ultrasound. Sonography practice is not regulated by the Health and Care Professions Council (HCPC), with no requirement to hold a formal qualification. The College of Podiatry does not currently define ultrasound training and competencies.This study aimed to determine the current use of ultrasound, training received and mentorship received and/or provided by podiatrists using ultrasound. A quantitative study utilising a cross-sectional, on-line, single-event survey was undertaken within the UK. Completed surveys were received from 284 podiatrists; 173 (70%) use ultrasound as part of their general practice, 139 (49%) for musculoskeletal problems, 131 (46%) for vascular assessment and 39 (14%) to support their surgical practice. Almost a quarter (n = 62) worked for more than one organisation; 202 (71%) were employed by the NHS and/or private sector (n = 118, 41%).Nearly all (93%) respondents report using a hand-held vascular Doppler in their daily practice; 216 (82%) to support decisions regarding treatment options, 102 (39%) to provide diagnostic reports for other health professionals, and 34 (13%) to guide nerve blocks.Ultrasound imaging was used by 104 (37%) respondents primarily to aid clinical decision making (n = 81) and guide interventions (steroid injections n = 67; nerve blocks n = 39). Ninety-three percent stated they use ultrasound imaging to treat their own patients, while others scan at the request of other podiatrists (n = 28) or health professionals (n = 18). Few use ultrasound imaging for research (n = 7) or education (n = 2).Only 32 (11%) respondents (n = 20 private sector) use therapeutic ultrasound to treat patients presenting with musculoskeletal complaints, namely tendon pathologies.Few respondents (18%) had completed formal post-graduate CASE (Consortium for the Accreditation of Sonographic Education) accredited ultrasound courses.Forty (14%) respondents receive ultrasound mentorship; the majority from fellow podiatrists (n = 17) or medical colleagues (n = 15). Over half (n = 127) who do not have ultrasound mentorship indicated they would like a mentor predominantly for ultrasound imaging. Fifty-five (19%) report they currently provide ultrasound mentorship for others. Understanding the scope of ultrasound practice, the training undertaken and the requirements for mentorship will underpin the development of competencies and recommendations defined by the College of Podiatry to support professional development and ensure safe practice.


Intramolecular crosslinking of monomeric fibrinogen by tissue transglutaminase.
In addition to generating polymeric products from human fibrinogen, human erythrocyte transglutaminase (protein-glutamine:amine gamma-glutamyltransferase, EC 126.96.36.199) was shown to catalyze the intramolecular reaction of crosslinking two of the constituent chains within monomeric fibrinogen itself. This internally fused protein derivative contains appreciable amounts of the N epsilon-(gamma-glutamyl)lysine bridge peptide and displays the A alpha.gamma hybrid chain pattern of crosslinking, characteristic for the actions of tissue transglutaminases on fibrinogen. Diagnostic analysis in pathological situations, where such enzymes might have escaped from cells into the plasma environment, should include a search for the internally crosslinked soluble fibrinogen monomer.


Flawed processing of airborne EM data affecting hydrogeological interpretation.
Airborne electromagnetics (AEMs) is increasingly being used across the globe as a tool for groundwater and environmental management. Focus is on ensuring the quality of the source data, their processing and modeling, and the integration of results with ancillary information to generate accurate and relevant products. Accurate processing and editing of raw AEM data, the topic of this article, is one of the crucial steps in obtaining quantitative information for groundwater modeling and management. In this article, we examine the consequences that different levels of processing of helicopter transient electromagnetic method data have on the resulting electrical models and subsequently on hydrogeological models. We focus on different approaches used in the industry for processing of the raw data and show how the electrical resistivity-depth models, which is the end "geophysical" product (after data inversion) of an AEM survey, change with different levels of processing of the raw data. We then extend the study to show the impact on some of the hydrogeological parameters or models, which can be derived from the geophysical results. The consequences of improper handling of raw data to groundwater and environmental management can be significant and expensive.


The use and rationale of selective alpha blockade in children with non-neurogenic neurogenic bladder dysfunction.
We present here a long-term observation of 2 children with a rare syndrome with a non-neurogenic neurogenic bladder dysfunction (Hinman's syndrome), and we investigated the safety and efficacy of long-term use of terazosine in association with prophylactic antibiotics, timed voiding and a bowel regimen. Two children, 7 years-old (22 kg) and 11 years-old (36 kg) presented in 1997 to our pediatric urology clinic with symptoms of urgency, frequency, urge incontinence and nocturnal enuresis. Both children were placed in a regimen of terazosine (starting with 0.5 mg increasing until 2 mg). There were no significant side effects throughout the entire treatment. The first 7-year old boy however developed some dizziness when the dose of terazosine was increased to 2 mg (after 4 weeks of administrating 1 mg), and this disappeared immediately when the dosage was reduced back to 1 mg daily. The urgency symptoms improved in both boys after 3 weeks of 1 mg terazosine. The secondary enuresis in the 11 year-old boy resolved after 2 months of 2 mg terazosine. It is possible to say that the alpha-blocker medication, terazosine can be administered safely to children with a non-neurogenic bladder dysfunction, also known as the Hinman's syndrome. These results have shown that dysfunctional voiding, postvoiding residual and upper tract involvement can disappear over time when long term terazosine is given in combination with timed voiding, prophylactic antibiotic therapy and treatment of the associated constipation. Our observations also suggest a permanent effect after discontinuing the medication.


[Adhesion molecules. Their role in cardiovascular physiopathology].
Adhesion molecules are membrane receptors that mediate several functions related to cell traffic, cell-cell interactions, and cell-matrix contact. There are three important groups associated to cardiovascular disease: integrins, selectins, and the immunoglobulin superfamily. They are involved in the endothelial disfunction and activation processes, and are related to the pathogenesis of coronary artery disease, reperfusion injury, allograft vasculopathy, myocarditis, hypertrophic myocardiopathy, etc. Also, they are related to the mechanism of action of statins. Serologic titer of these molecules has diagnostic and predictive value on diverse cardiovascular diseases. This review focuses on the functions of adhesins and discusses various therapeutic possibilities based on their recognition.


Clinical Practice Variations in the Management of Ischemia With No Obstructive Coronary Artery Disease.
Background Ischemia with no obstructive coronary artery disease is a condition associated with major adverse cardiovascular outcomes. To date, there are no specific American Heart Association or American College of Cardiology guidelines. The objective of this survey is to better understand the clinical practice and knowledge gaps that exist nationally. Methods and Results Participant-specific links for a survey with 11 questions and 3 reminders were sent between September and October 2020 to the American College of Cardiology CardioSurve Panel. The panel consist of randomly selected cardiologists (n=437) who represent the current profile of the American College of Cardiology US membership. The survey received a 30% response rate. Of the 172 respondents, 130 (76%) indicated that they have treated patients with ischemia with no obstructive coronary artery disease. Although the majority (69%) are generally confident in their ability to manage this condition, 1 of 3 report lack of confidence or are neutral. The American College of Cardiology/American Heart Association Chronic Stable Angina Guidelines are the most commonly used reference for treating ischemia with no obstructive coronary artery disease (81%), with most cardiologists wanting additional clinical guidance, such as randomized controlled trials (61%). More than 4 of 5 cardiologists rarely or never order advanced imaging modalities to assess coronary flow reserve. Approximately 2 of 3 of respondents frequently prescribe statins (68%), aspirin (66%), calcium channel blockers (63%), and β blockers or α/β blockers (55%). However, nearly 70% never prescribe angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Conclusions This survey demonstrates heterogeneity in the management of ischemia with no obstructive coronary artery disease among US cardiologists, identifies support for guideline development, and outlines knowledge gaps for research and education in the therapeutic management of this condition.


[Some micromycetes isolated from spoiled food and soil in Argentine Antarctica].
The main objective of this study was to identify some micro fungi isolated from soil of Potter peninsula (Antarctica), which were involved in food spoiling at Jubany base. Different solid culture media were used to isolate 66 fungal strains from spoiled food and soil. Twelve saprophytic, spoiling and/or toxicogenic taxa belonging to the genera Doratomyces, Geomyces, Oidiodendron y Penicillium were identified; eight of them with full descriptions and drawings. This is the first record of Geomyces pannorum var. vinaceus and Oidiodendron griseum recovered from the Argentine Antarctica.


Gelatin implants in scleral buckling procedures.
In 375 scleral buckling procedures, an absorbable gelatin implant (Retina Gelfilm) was used. This series included 192 trapdoor and scleral pouch procedures, and 183 operations in which a gelatin implant was used beneath a silicone rubber implant. Two thicknesses of gelatin implants were used, 0.5 mm and 0.75 mm. Absorption time varied from 2 to 24 months, depending on the thickness of the implant and whether it was used alone or beneath a silicone rubber implant. Gelatin is an excellent absorbable implant when used alone or under a silicone rubber implant in selected patients with retinal detachment to produce a temporary elevation or posterior extension of the buckle, or both.


Stimulants of Toll-like receptor (TLR)-2 and TLR-4 are abundant in certain minimally-processed vegetables.
Stimulants of the innate immune receptors Toll-like receptor (TLR)-2 and TLR4 have been shown to promote insulin resistance and atherosclerosis in animal models of these diseases. As minimally processed vegetables (MPV) can contain a relatively large bacterial load compared to other foodstuffs, we aimed to quantify the abundance of stimulants of TLR2 and TLR4 in MPV using a transfection-based bioassay calibrated with Escherichia coli LPS and the synthetic lipopeptide Pam(3)CSK(4). Of 5 classes of MPV and 3 classes of related vegetable products considered to be likely to contain a high microbial load, diced onion and bean sprouts contained the highest levels of stimulants of TLR2 (up to 18.5 μg Pam(3)CSK(4)-equivalents per g) and TLR4 (up to 11.4 μg LPS-equivalents per g). By contrast, the majority of fresh whole vegetables examined reproducibly contained minimal or undetectable levels of TLR2- or TLR4-stimulants. The accumulation of TLR-stimulants in MPVs correlated well with growth of enterobacterial spoilage organisms. In conclusion, the modern trend towards eating minimally processed vegetables rather than whole foods is likely to be associated with increased oral exposure to stimulants of TLR2 and TLR4.


Thromboembolism in orthopaedics--observation and experiment.
Surgical science has evolved from the meticulously recorded anatomical and pathological experiments applied by Hunter to the use of large observational studies and randomised clinical trials. These modern epidemiological techniques, supported by appropriate statistics, are helping us to answer many questions in surgery. Perhaps nowhere in surgery have these techniques been applied as thoroughly as in orthopaedic thromboembolism.


Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination and Autism Spectrum Disorder.
: media-1vid110.1542/5803567555001PEDS-VA_2018-0120Video Abstract BACKGROUND: Increasing vaccination of pregnant women makes it important to assess safety events potentially linked to prenatal vaccination. This study investigates the association between prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination and autism spectrum disorder (ASD) risk in offspring. This is a retrospective cohort study of mother-child pairs with deliveries January 1, 2011 to December 31, 2014 at Kaiser Permanente Southern California hospitals. Maternal Tdap vaccination from pregnancy start to delivery date was obtained from electronic medical records. A diagnosis of ASD was obtained by using International Classification of Diseases, Ninth and Tenth Revision codes. Children were managed from birth to first ASD diagnosis, end of membership, or end of follow-up (June 30, 2017). Cox proportional hazards models estimated the unadjusted and adjusted hazard ratios (HRs) for the association between maternal Tdap vaccination and ASD, with inverse probability of treatment weighting to adjust for confounding. Women vaccinated were more likely to be Asian American or Pacific Islander, be nulliparous, have a higher education, receive influenza vaccination prenatally, and give birth at term. ASD was diagnosed in 1341 (1.6%) children, and the incidence rate was 3.78 per 1000 person years in the Tdap exposed and 4.05 per 1000 person years in the unexposed group (HR: 0.98, 95% confidence interval: 0.88-1.09). The inverse probability of treatment weighting-adjusted analyses revealed that prenatal Tdap vaccination was not associated with an increased ASD risk (HR: 0.85, 95% confidence interval: 0.77-0.95). Prenatal Tdap vaccination was not associated with an increased ASD risk. We support recommendations to vaccinate pregnant women to protect infants, who are at highest risk of death after pertussis infection.


Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatments (ALS-SSIT) for Evaluating Therapeutic Effect of Traditional Chinese Medicine: A Prospective Study.
To evaluate the reliability, validity, sensitivity, and clinical applicability of a new scale-the amyotrophic lateral sclerosis symptom score in integrative treatments (ALS-SSIT)-for measuring the effect of traditional Chinese medicine (TCM) in patients with amyotrophic lateral sclerosis (ALS). A total of 160 patients with ALS were enrolled and followed up for 6 months. All patients received TCM. Patients were evaluated at enrollment and at the end of 6 months with a new scale, the ALS-SSIT, developed after extensive consultations with TCM experts with several years of experience in the treatment of ALS. The 36-item Medical Outcomes Study Short Form (SF-36) scale and the amyotrophic lateral sclerosis functional rating scale (ALSFRS) were used as the reference standards. The acceptance rate and completion rate of the ALS-SSIT scale were high, and the content validity was confirmed by experts. Test-retest performed at enrollment and at 6 months showed good reliability of the ALS-SSIT scale (Cronbach α, 0.9172 and 0.9181, respectively). The ALS-SSIT scale score showed significant change at 6 months, indicating the ability to reflect the change in disease severity. The ALS-SSIT appears to be a feasible, reliable, and sensitive tool for the evaluation of the effect of TCM in patients with ALS.


Primary granule exocytosis in human neutrophils is regulated by Rac-dependent actin remodeling.
The actin cytoskeleton regulates exocytosis in all secretory cells. In neutrophils, Rac2 GTPase has been shown to control primary (azurophilic) granule exocytosis. In this report, we propose that Rac2 is required for actin cytoskeletal remodeling to promote primary granule exocytosis. Treatment of neutrophils with low doses (< or = 10 microM) of the actin-depolymerizing drugs latrunculin B (Lat B) or cytochalasin B (CB) enhanced both formyl peptide receptor- and Ca(2+) ionophore-stimulated exocytosis. Higher concentrations of CB or Lat B, or stabilization of F-actin with jasplakinolide (JP), inhibited primary granule exocytosis measured as myeloperoxidase release but did not affect secondary granule exocytosis determined by lactoferrin release. These results suggest an obligatory role for F-actin disassembly before primary granule exocytosis. However, lysates from secretagogue-stimulated neutrophils showed enhanced actin polymerization activity in vitro. Microscopic analysis showed that resting neutrophils contain significant cortical F-actin, which was redistributed to sites of primary granule translocation when stimulated. Exocytosis and actin remodeling was highly polarized when cells were primed with CB; however, polarization was reduced by Lat B preincubation, and both polarization and exocytosis were blocked when F-actin was stabilized with JP. Treatment of cells with the small molecule Rac inhibitor NSC23766 also inhibited actin remodeling and primary granule exocytosis induced by Lat B/fMLF or CB/fMLF, but not by Ca(2+) ionophore. Therefore, we propose a role for F-actin depolymerization at the cell cortex coupled with Rac-dependent F-actin polymerization in the cell cytoplasm to promote primary granule exocytosis.


Extraction of maxillary canines: Esthetic perceptions of patient smiles among dental professionals and laypeople.
Maxillary canines are generally considered important both cosmetically and functionally. Most claims on the importance of maxillary canines, however, have been based on expert opinions and clinician-based studies. There are no scientific studies in the literature reporting on their cosmetic importance or how laypeople perceive a smile treated by maxillary canine extractions. Our objective was to investigate whether there is any difference in the perceptions of patients' smiles treated by extracting either maxillary canines or first premolars, as judged by orthodontists, dentists, and laypeople. This retrospective study included 24 participants who had unilateral or bilateral extraction of maxillary permanent canines and fixed appliances in the maxillary and mandibular arches to comprehensively correct the malocclusion, selected from orthodontic patients treated at Chesterfield Royal Hospital NHS trust in the United Kingdom over the last 20 years. The control group of patients had extraction of maxillary first premolars followed by fixed appliances and finished to an extremely high standard judged by the requirement that they had been submitted for the Membership in Orthodontics examination. The finished Peer Assessment Rating scores for this group were less than 5. The end-of-treatment frontal extraoral smiling and frontal intraoral views were presented for both groups. The photographs were blinded for extraction choice and standardized for size and brightness using computer software (Adobe Photoshop CC version 14.0; Adobe Systems, San Jose, Calif). The work file was converted to an editable pdf file and e-mailed to the assessors. The assessor panel consisted of 30 members (10 orthodontists, 10 dentists, and 10 laypeople), who were purposely selected. The measures were rated on a 10-point Likert scale. The attractiveness ratings were not statistically significantly different between the canine extraction and premolar extraction groups, with a mean difference of 0.33 (SD, 0.29) points. A 1-way repeated-measures analysis of variance to test the difference in scores among the laypeople, orthodontists, and dentists (n = 30) showed no statistically significant difference (Wilks lambda = 0.835; P = 0.138), and the Bonferroni test indicated that no pair-wise difference was statistically significant. No statistically significant difference was found in the smile attractiveness between canine extraction and premolar extraction patients as assessed by general dentists, laypeople, and orthodontists. Further high-quality studies are required to evaluate the effect of canine extraction and premolar substitution on functional occlusion.


Morphic Sensors for Respiratory Parameters Estimation: Validation against Overnight Polysomnography.
Effective monitoring of respiratory disturbances during sleep requires a sensor capable of accurately capturing chest movements or airflow displacement. Gold-standard monitoring of sleep and breathing through polysomnography achieves this task through dedicated chest/abdomen bands, thermistors, and nasal flow sensors, and more detailed physiology, evaluations via a nasal mask, pneumotachograph, and airway pressure sensors. However, these measurement approaches can be invasive and time-consuming to perform and analyze. This work compares the performance of a non-invasive wearable stretchable morphic sensor, which does not require direct skin contact, embedded in a t-shirt worn by 32 volunteer participants (26 males, 6 females) with sleep-disordered breathing who performed a detailed, overnight in-laboratory sleep study. Direct comparison of computed respiratory parameters from morphic sensors versus traditional polysomnography had approximately 95% (95 ± 0.7) accuracy. These findings confirm that novel wearable morphic sensors provide a viable alternative to non-invasively and simultaneously capture respiratory rate and chest and abdominal motions.


Changes in compliance with school-based physical activity recommendations in Spanish youth: The UP&DOWN longitudinal study.
The study aimed (a) to examine changes in physical activity (PA) during the whole day, school hours, recess, and physical education classes (PEC) during a 2-year period in primary and secondary students; (b) to identify changes in the proportion of compliance with specific PA recommendations for these periods; and (c) to examine whether PA levels at baseline are associated with PA levels 2 years later. Eight hundred and fourteen (51.8% boys) children and 658 (50.1% boys) adolescents from 41 Spanish schools participated in the study. Hip-worn accelerometers were used to assess PA during different time periods. Light PA (LPA) declined during the whole day, school hours, recess (all P < 0.001, except child girls for recess), and PEC (all, P < 0.05) in children and adolescents. Moderate-to-vigorous PA (MVPA) during the whole day and recess declined in child boys (P < 0.01 and P < 0.001, respectively) and adolescent boys (P < 0.001 and P < 0.05, respectively). MVPA during PEC declined in adolescent boys (P < 0.001) and adolescent girls (all P < 0.05). The proportion of compliance with the specific PA recommendations for these periods declined (P < 0.05), except for PEC in adolescent girls. PA during the whole day at baseline was moderately associated with PA during the whole day years later (ICCs = 0.210-0.544, with one exception), but this association was lower for the school-based PA. In conclusion, time spent in MVPA and LPA during the whole day and recess declined over time in child and adolescent boys and during PEC in adolescents. These findings highlight the need to promote PA interventions in these settings.


[Optimization of the antibiotics policy in the Netherlands. II. SWAB guidelines for the antimicrobial therapy of pneumonia in patients at home and as nosocomial infections. The Netherlands Antibiotic Policy Foundation].
The Netherlands Antibiotic Policy Foundation issued guidelines for empirical antimicrobial therapy of adult pneumonia patients in hospitals. A distinction is made between pneumonia contracted at home or in hospital because of the differences in micro-organisms and resistance patterns. These two categories are subdivided further with an empirical antibiotic treatment being chosen on the basis of the causative agents to be expected. For instance, pneumonia contracted at home is mostly caused by Streptococcus pneumoniae, to be treated with benzylpenicillin or amoxicillin. With regard to nosocomial pneumonia, treatment varies according to whether a pneumonia has or has not been contracted in the intensive care unit. Combating development of resistance is alloted an important place. Emphasis is laid on 'streamlining' the therapy, i.e. its adjustment (including choosing an antibiotic with the narrowest possible spectrum) once the causative agent is known.


A geographic cline of skull and brain morphology among individuals of European Ancestry.
Human skull and brain morphology are strongly influenced by genetic factors, and skull size and shape vary worldwide. However, the relationship between specific brain morphology and genetically-determined ancestry is largely unknown. We used two independent data sets to characterize variation in skull and brain morphology among individuals of European ancestry. The first data set is a historical sample of 1,170 male skulls with 37 shape measurements drawn from 27 European populations. The second data set includes 626 North American individuals of European ancestry participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with magnetic resonance imaging, height and weight, neurological diagnosis, and genome-wide single nucleotide polymorphism (SNP) data. We found that both skull and brain morphological variation exhibit a population-genetic fingerprint among individuals of European ancestry. This fingerprint shows a Northwest to Southeast gradient, is independent of body size, and involves frontotemporal cortical regions. Our findings are consistent with prior evidence for gene flow in Europe due to historical population movements and indicate that genetic background should be considered in studies seeking to identify genes involved in human cortical development and neuropsychiatric disease.


Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.


Altered resting-state intra- and inter- network functional connectivity in patients with persistent somatoform pain disorder.
Patients with persistent somatoform pain disorder (PSPD) usually experience various functional impairments in pain, emotion, and cognition, which cannot be fully explained by a physiological process or a physical disorder. However, it is still not clear for the mechanism underlying the pathogenesis of PSPD. The present study aimed to explore the intra- and inter-network functional connectivity (FC) differences between PSPD patients and healthy controls (HCs). Functional magnetic resonance imaging (fMRI) was performed in 13 PSPD patients and 23 age- and gender-matched HCs. We used independent component analysis on resting-state fMRI data to calculate intra- and inter-network FCs, and we used the two-sample t-test to detect the FC differences between groups. Spearman correlation analysis was employed to evaluate the correlations between FCs and clinical assessments. As compared to HCs, PSPD patients showed decreased coactivations in the right superior temporal gyrus within the anterior default-mode network and the anterior cingulate cortex within the salience network, and increased coactivations in the bilateral supplementary motor areas within the sensorimotor network and both the left posterior cingulate cortex and the medial prefrontal cortex within the anterior default-mode network. In addition, we found that the PSPD patients showed decreased FNCs between sensorimotor network and audio network as well as visual network, between default-mode network and executive control network as well as audio network and between salience network and executive control network as well as right frontoparietal network, and increased FNCs between sensorimotor network and left frontoparietal network, salience network as well as cerebellum network, which were negatively correlated with the clinical assessments in PSPD patients. Our findings suggest that PSPD patients experience large-scale reorganization at the level of the functional networks, which suggests a possible mechanism underlying the pathogenesis of PSPD.


Sesamol down-regulates the lipopolysaccharide-induced inflammatory response by inhibiting nuclear factor-kappa B activation.
We examined the effects of sesamol on the lipopolysaccharide (LPS)-induced inflammatory response. Sesamol inhibited serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitrite production in LPS-treated mice, and inhibited LPS-induced inducible nitric oxide synthase expression in mouse leukocytes. Sesamol also down-regulated TNF-α, IL-1β, and nitrite production as well as inducible nitric oxide synthase expression in LPS-treated RAW 264.7 cells. Further, sesamol inhibited LPS-induced nuclear factor (NF)-κB translocation and inhibitor (I)κB-α phosphorylation in RAW 264.7 cells. By inhibiting TNF-α, IL-1β, and nitrite levels, and interfering with the NFκB pathway, sesamol down-regulated the LPS-initiated inflammatory response.


Intra-aortic balloon occlusion to salvage patients with life-threatening hemorrhagic shocks from pelvic fractures.
The purpose of this study was to describe a blinded intra-aortic balloon occlusion (IABO) procedure in pelvic fractures (PF) for patients with critically uncontrollable hemorrhagic shock (CUHS). Of 2,064 patients treated for PF, 13 underwent IABO during initial resuscitation to control massive pelvic bleeding leading to CUHS. Our IABO procedure consists of internal aortic occlusion without fluoroscopy, using a latex balloon inflated in the infrarenal aorta. Retrospectively collected data included demographics, fracture classification, additional injuries, blood transfusions, surgical interventions, angiographic procedure, physiologic parameters, and survival. All balloons were successfully placed, and a significant increase in systolic blood pressure (70 mm Hg, p = 0.001) was observed immediately after IABO. Twelve of 13 patients became transferrable. Angiography performed after IABO was positive for arterial injury in 92% of patients, and 9 patients benefitted from arterial embolization. Survival rate was 46% (6 of 13) and was inversely related to the length of inflation (p = 0.026) and the mean Injury Severity Score (p = 0.011). This IABO procedure can be life saving in the management of patients with CUHS from PF, permitting transport to angiography. However, the decision for such treatment must be as quickly as possible after trauma to reduce the time of occlusion.


The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials.
We updated our previous systematic review of the effect of supplemental calcium on blood pressure. We extended our previous searches on MEDLINE and EMBASE to May 1997 and examined citations from relevant articles. We contacted the authors of eligible trials to ensure the accuracy and completeness of data, and to identify unpublished trials. We included any study in which investigators randomized hypertensive or normotensive people to calcium supplementation or alternative therapy and measured blood pressure for at least 2 weeks. In addition to 32 trials included in the prior metaanalysis, 10 new trials contributed to this metaanalysis. Two pairs of independent reviewers abstracted data and assessed the validity of the study data according to six quality criteria. We calculated the differences in blood pressure change between the calcium supplementation and control groups and pooled the estimates with each trial weighted with the inverse of the variance using a random effects model. The predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodologic quality of the studies. The pooled analysis shows a reduction in systolic blood pressure of -1.44 mm Hg (95% confidence interval -2.20 to -0.68; P < .001) and in diastolic blood pressure of -0.84 mm Hg (95% confidence interval -1.44 to -0.24; P < .001). We found statistically significant heterogeneity of results across trials (P < or = .02), which persisted when we looked at the nondietary trials alone, but not when we restricted our analysis to dietary trials. Although there was a trend toward larger effects with dietary interventions, none of the possible mediators of blood pressure reduction explained differences in treatment effect. We conclude that calcium supplementation leads to a small reduction in systolic and diastolic blood pressure. The effect of supplemental calcium in the diet is at least as great as nondietary supplementation.


Pd-catalyzed oxidative cross-coupling of perfluoroarenes with aromatic heterocycles.
A straightforward and practical method for direct Pd(OAc)(2)-catalyzed oxidative cross-coupling of electron-deficient perfluoroarenes with aromatic heterocycles has been developed. Because of its low catalyst loading (2.5 mol %), high reaction efficiency, good chemo- and regioselectivity, and excellent functional-group compatibility, this protocol provides a useful and operationally simple access to perfluoroarene-thiophene structures of interest in functional materials for electronic devices.


Effectiveness of emotional skills training for patients with anorexia nervosa with autistic symptoms in group and individual format.
The aim of this study was to examine the effectiveness of CREST interventions in individual and group formats for adult anorexia nervosa. Furthermore, this study also aims to analyse whether patients with high levels of autistic symptoms respond differently. Participants' self-report measures were taken before and after individual and group interventions (N = 66 and N = 62, respectively). Mixed effects analysis was used to analyse overall response to both formats and assess interaction with autism symptoms. Significant improvements were observed for patients' alexithymia in individual format, and motivation increased for participants in both interventions. Significant interactions were observed between alexithymia, social anhedonia, and autism symptoms in individual format and alexithymia in group format. No interactions between autism and time were observed for either format. CREST in both formats offers participants improvements in social-emotional and motivational domains. Patients with high levels of autism symptoms also score high on both social anhedonia and alexithymia measures, but this does not affect their response to treatment.