Molecular dynamics simulation of the rupture mechanism in nanorod filled polymer nanocomposites.
Through coarse-grained molecular dynamics simulation, we aim to uncover the rupture mechanism of polymer-nanorod nanocomposites by characterizing the structural and dynamic changes during the tension process. We find that the strain at failure is corresponding to the coalescence of a single void into larger voids, namely the change of the free volume. And the minimum of the Van der Walls (VDWL) energy reflects the maximum mobility of polymer chains and the largest number of voids of polymer nanocomposites. After the failure, the stress gradually decreases with the strain, accompanied by the contract of the highly orientated polymer bundles. In particular, we observe that the nucleation of voids prefers to occur from where the ends of polymer chains are located. We systematically study the effects of the interfacial interaction, temperature, the length and volume fraction of nanorods, chain length, bulk cross-linking density and interfacial chemical bonds on the rupture behavior, such as the stress at failure, the tensile modulus and the rupture energy. The rupture resistance ability increases with the increase of the interfacial interaction, rod length, and bulk cross-linking density. With an increase in the interfacial interaction, it induces the rupture transition from mode A (no bundles) to B (bundles). The transition point of the stress at failure as a function of the temperature roughly corresponds to the glass transition temperature. At longer chain length, a non-zero stress plateau occurs. And excessive chemical bonds between polymers and nanorods are harmful to the rupture property. We find that an optimal volume fraction of nanorods exists for the stress-strain behavior, which can be rationalized by the formation of the strongest polymer-nanorod network, leading to the slowest mobility of nanorods.


Nonlinear dynamics in meso and nano scales: fundamental aspects and applications.
This introduction to the special issue, Nonlinear dynamics in meso and nano scales: fundamental aspects and applications, gives a short overview about different contexts and current challenges posed by the emergence of nonlinearities at meso and nano characteristic sizes. It also addresses different aspects related to classical and quantum chaos. Moreover, it comments on the articles in this thematic publication, briefly summarizing their relevance in helping to understand the uprise of chaos and complex behaviour at those small scales.


[Experimental infection of Aedes albopictus mosquitoes by a spiroplasma strain isolated from Culex annulus in Taiwan].
Two Aedes albopictus strains are infected by one of the four presently known mosquito spiroplasma strains, the CUAS-1 strain isolated from Culex annulus from Taïwan. An infection by intra-thoracic inoculation leads to a pathogenic effect, dose-dependent, the longevity of mosquitoes being shortened. This pathogenicity is observed at various time after inoculation depending of the mosquito strain. On the other hand, an oral infection has no consequence on the longevity of infected females. However, the replication of spiroplasma has been demonstrated with both infection procedures.


Approach and avoidance towards aggressive stimuli and its relation to reactive and proactive aggression.
This study assessed the association between indirectly measured behavioural approach- and avoidance-related tendencies on the one hand, and reactive versus proactive aggression on the other hand. Reactive aggression (i.e. the impulsive, anger-driven aggression expressed in response to threatening stimuli) was differentiated from proactive aggression (i.e. the more controlled aggression motivated towards obtaining specific goals). A mixed sample of 118 patients and healthy controls filled out a self-report measure to assess their degree of reactive and proactive aggression, and then performed an Approach Avoidance Task in which they were asked to pull or push a joystick in response to a format-feature of a series of pictures, irrespective of their contents. The pictorial stimuli used in this task included attack-related scenes and angry faces, along with neutral, positive and negative control stimuli. The results were controlled for the level of personality disorder pathology, gender, and age. The findings indicated that reactive but not proactive aggression was related to the relative behavioural tendency to approach attack-related scenes, along with positive stimuli. These findings reflect the hyper-reactivity of the approach-related reward system in reactive aggression, and further our knowledge into the distinct correlates and precursors of reactive and proactive aggression.


In situ monitoring of vapour-induced assembly of pharmaceutical cocrystals using a benchtop powder X-ray diffractometer.
We describe a simple setup for in situ continuous monitoring of vapour-induced transformations of organic solids using a benchtop powder X-ray diffractometer. Proof-of-principle application of this setup to model pharmaceutical cocrystals reveals complex reactivity, transformations of reaction intermediates within minutes, and a simple route to the rarely observed monoclinic form of the pharmaceutical cocrystal of carbamazepine and saccharin.


Dopamine D1 receptor interaction with arrestin3 in neostriatal neurons.
Dopamine D1 receptor interactions with arrestins have been characterized using heterologously expressed D1 receptor and arrestins. The purpose of this study was to investigate the interaction of the endogenous D1 receptor with endogenous arrestin2 and 3 in neostriatal neurons. Endogenous arrestin2 and 3 in striatal homogenates bound to the C-terminus of the D1 receptor in a glutathione-S-transferase (GST) pulldown assay, with arrestin3 binding more strongly. The D1 C-terminus and, to a lesser extent, the third cytoplasmic loop also bound purified arrestin2 and 3. In neostriatal neurons, 2, 5, and 20 min agonist treatment increased the colocalization of the D1 receptor and arrestin3 immunoreactivity without altering the colocalization of the D1 receptor and arrestin2. Further, agonist treatment for 5 and 20 min caused translocation of arrestin3, but not arrestin2, to the membrane. The binding of arrestin3, but not arrestin2, to the D1 receptor was increased as assessed by coimmunoprecipitation after agonist treatment for 5 and 20 min. Agonist treatment of neurons induced D1 receptor internalization (35-45%) that was maximal within 2-5 min, a time-course similar to that of the increase in colocalization of the D1 receptor with arrestin3. These data indicate that the D1 receptor preferentially interacts with arrestin3 in neostriatal neurons.


Role of vitamin B 6 biosynthetic rate in the study of vitamin B 6 synthesis in Escherichia coli.
Nutritional auxotrophs of Escherichia coli synthesize vitamin B(6) compounds at a rate of 1 x 10(-10) to 2 x 10(-10) moles per hr per mg (dry weight) of cells when they are suspended in minimal medium lacking their required nutrients. A few auxotrophs have been found to stop or reduce vitamin B(6) synthesis during such an experiment. These include thiamineless, citrate synthaseless, and pyridoxineless mutants as well as mutants which require four carbon compounds for growth. Glycolaldehyde was found to restore vitamin B(6) synthesis in the last named of these mutants without restoring normal growth. A class of pyridoxineless mutants which responded with normal growth to 0.4 mm glycolaldehyde or 0.15 x 10(-3) mm pyridoxol was also found. The results suggest that a thiamine pyrophosphate-requiring step as well as glycolaldehyde may be involved in pyridoxal phosphate biosynthesis.


Functional antagonists of sonic hedgehog reveal the importance of the N terminus for activity.
During development, sonic hedgehog functions as a morphogen in both a short-range contact-dependent and in a long-range diffusable mode. Here, we show using a panel of sonic hedgehog variants that regions near the N terminus of the protein play a critical role in modulating these functions. In the hedgehog responsive cell line C3H10T1/2, we discovered that not only were some N-terminally truncated variants inactive at eliciting a hedgehog-dependent response, but they competed with the wild-type protein for function and therefore served as functional antagonists. These variants were indistinguishable from wild-type sonic hedgehog in their ability to bind the receptor patched-1, but failed to induce the hedgehog-responsive markers, Gli-1 and Ptc-1, and failed to promote hedgehog-dependent differentiation of the cell line. They also failed to support the adhesion of C3H10T1/2 cells to hedgehog-coated plates under conditions where wild-type sonic hedgehog supported binding. Structure-activity data indicated that the N-terminal cysteine plays a key regulatory role in modulating hedgehog activity. The ability to dissect patched-1 binding from signaling events in C3H10T1/2 cells suggests the presence of unidentified factors that contribute to hedgehog responses.


Scar Prevention and Enhanced Wound Healing Induced by Polydeoxyribonucleotide in a Rat Incisional Wound-Healing Model.
High-mobility group box protein-1 (HMGB-1) plays a central role in the inflammatory network, and uncontrolled chronic inflammation can lead to excessive scarring. The aim of this study was to evaluate the anti-inflammatory effects of polydeoxyribonucleotide (PDRN) on scar formation. Sprague-Dawley rats (n = 30) underwent dorsal excision of the skin, followed by skin repair. PDRN (8 mg/kg) was administered via intraperitoneal injection for three (PDRN-3 group, n = 8) or seven (PDRN-7 group, n = 8) days, and HMGB-1 was administered via intradermal injection in addition to PDRN treatment for three days (PDRN-3+HMGB-1 group; n = 6). The scar-reducing effects of PDRN were evaluated in the internal scar area and by inflammatory cell counts using histology and immunohistochemistry. Western blot, immunohistochemistry and immunofluorescence assays were performed to observe changes in type I and type III collagen and the expression of HMGB-1 and CD45. Treatment with PDRN significantly reduced the scar area, inflammatory cell infiltration and the number of CD45-positive cells. In addition, the increased expression of HMGB-1 observed in the sham group was significantly reduced after treatment with PDRN. Rats administered HMGB-1 in addition to PDRN exhibited scar areas with inflammatory cell infiltration similar to the sham group, and the collagen synthesis effects of PDRN were reversed. In summary, PDRN exerts anti-inflammatory and collagen synthesis effects via HMGB-1 suppression, preventing scar formation. Thus, we believe that the anti-inflammatory and collagen synthesis effects of PDRN resulted in faster wound healing and decreased scar formation.


[Habitat selection attributes of giant panda].
Based on the 1997-2009 inventory data of Wanglang Nature Reserve, the habitat selection attributes of giant panda were studied from the aspects of topography, forest community structure, and main feeding bamboo by the methods of frequency distribution and Bailey. The giant panda had obvious habitat preferences. Topographically, the preferred microhabitat was on the even or convex slopes at the ridge, top, or middle part of mountain body at an elevation 2500-3000 m, with southwest aspect, 6 degrees-30 degrees, and the distance to the nearest water source > 300 m. As for the forest community structure, the giant panda preferred the microhabitat with the bamboo succeeded from secondary forest or mixed conifer and broad-leaved forest, and with the average tree height being 20-29 m and the shrub coverage being 0-24%. The preferred main feeding bamboo by the giant panda was the growing well Fargesia denudate with an average height of 2-5 m and the coverage of > 50%.


Reducing unnecessary vitamin testing in general practice: barriers and facilitators according to general practitioners and patients.
There has been an increase in testing of vitamins in patients in general practice, often based on irrational indications or for non-specific symptoms, causing increasing healthcare expenditures and medicalisation of patients. So far, there is little evidence of effective strategies to reduce this overtesting in general practice. Therefore, the aim of this qualitative study was to explore the barriers and facilitators for reducing the number of (unnecessary) vitamin D and B12 laboratory tests ordered. This qualitative study, based on a grounded theory design, used semistructured interviews among general practitioners (GPs) and patients from two primary care networks (147 GPs, 195 000 patients). These networks participated in the Reducing Vitamin Testing in Primary Care Practice (REVERT) study, a clustered randomized trial comparing two de-implementation strategies to reduce test ordering in primary care in the Netherlands. Twenty-one GPs, with a maximum of 1 GP per practice who took part in the REVERT study, and 22 patients (who were invited by their GP during vitamin-related consultations) were recruited, from which 20 GPs and 19 patients agreed to participate in this study. The most important factor hampering vitamin-test reduction programmes is the mismatch between patients and medical professionals regarding the presumed appropriate indications for testing for vitamin D and B12. In contrast, the most important facilitator for vitamin-test reduction may be updating GPs' knowledge about test indications and their awareness of their own testing behaviour. To achieve a sustainable reduction in vitamin testing, guidelines with clear and uniform recommendations on evidence-based indications for vitamin testing, combined with regular (individual) feedback on test-ordering behaviour, are needed. Moreover, the general public needs access to clear and reliable information on vitamin testing. Further research is required to measure the effect of these strategies on the number of vitamin test requests. WAG/mb/16/039555.


[Current data on the bacteriology of leprosy].
Microscopic examination and mouse foot-pad inoculation are the main tools in Mycobacterium leprae bacteriology. Microscopic examination enables to calculate bacteriological (IB) and morphological (IM) indexes. The former scores the density of acid-fast organisms in the lesions and the latter scores their viability since only solidly stained acid-fast organisms are likely to be alive. Mouse foot-pad inoculation provides the opportunity for studying the growth curve of M. leprae. Alterations of this growth curve under drug therapy enable to assess the antileprosy activity of drugs and to determine the drug sensitivity of organisms. Acquired and primary drug resistances to DDS are to date the most important events in the chemotherapy of leprosy. Researches are in progress on mice with congenitally reduced immunological capacity (nu/nu mice) and on antileprosy vaccination. Although no decisive advances have been obtained in these fields, researches in progress are promising.


Production of heparan sulphate proteoglycans by human bone marrow stromal cells.
Haemopoietic progenitors from human bone marrow bind strongly to human marrow stromal cell cultures but the interaction only occurs if the stromal cells are maintained in methyl prednisolone. Heparan sulphate has been implicated in this interaction and in the binding of haemopoietic cell growth factors. In the present study we have compared the molecular structures of the heparan sulphate proteoglycans, metabolically labelled with [35S]sulphate, produced by methyl prednisolone-treated and untreated human marrow stromal cells in vitro. [35S]proteoglycans were examined in the cell layers (extracted with 1% (v/v) Triton X-100 in 6 M urea) and in the culture medium. Fractionation of proteoglycans by ion-exchange chromatography indicated that the heparan sulphate produced by the treated cultures eluted at a higher NaCl concentration than the counterpart from untreated cells. The heparan sulphate appeared to be mainly expressed on the cell surface, since it was efficiently extracted by treatment with dilute trypsin (50 micrograms ml-1 for 10 min). All cultures contained two heparan sulphate proteoglycan species, the major component eluted from a Sepharose CL-4B column with a median Kav of 0.33 and apparently contained an average of only one heparan sulphate chain. Small quantities of a larger proteoglycan, which was eluted in the void volume from the CL-4B column, was also detected, mainly in the cell layer extracts. The molecular structure of the heparan sulphate chains was analysed by oligosaccharide mapping, following specific enzymic depolymerisation, and separation of breakdown products by gradient PAGE. The maps revealed significant differences in overall enzyme susceptibilities and sulphation patterns of polysaccharides produced by methyl prednisolone-treated and untreated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)


Longitudinal homogenization of the microbiome between both occupants and the built environment in a cohort of United States Air Force Cadets.
The microbiome of the built environment has important implications for human health and wellbeing; however, bidirectional exchange of microbes between occupants and surfaces can be confounded by lifestyle, architecture, and external environmental exposures. Here, we present a longitudinal study of United States Air Force Academy cadets (n = 34), which have substantial homogeneity in lifestyle, diet, and age, all factors that influence the human microbiome. We characterized bacterial communities associated with (1) skin and gut samples from roommate pairs, (2) four built environment sample locations inside the pairs' dormitory rooms, (3) four built environment sample locations within shared spaces in the dormitory, and (4) room-matched outdoor samples from the window ledge of their rooms. We analyzed 2,170 samples, which generated 21,866 unique amplicon sequence variants. Linear convergence of microbial composition and structure was observed between an occupants' skin and the dormitory surfaces that were only used by that occupant (i.e., desk). Conversely, bacterial community beta diversity (weighted Unifrac) convergence between the skin of both roommates and the shared dormitory floor between the two cadet's beds was not seen across the entire study population. The sampling period included two semester breaks in which the occupants vacated their rooms; upon their return, the beta diversity similarity between their skin and the surfaces had significantly decreased compared to before the break (p < 0.05). There was no apparent convergence between the gut and building microbiota, with the exception of communal bathroom door-handles, which suggests that neither co-occupancy, diet, or lifestyle homogenization had a significant impact on gut microbiome similarity between these cadets over the observed time frame. As a result, predictive classifier models were able to identify an individual more accurately based on the gut microbiota (74%) compared to skin (51%). To the best of our knowledge, this is the first study to show an increase in skin microbial similarity of two individuals who start living together for the first time and who are not genetically related or romantically involved. Cohabitation was significantly associated with increased skin microbiota similarity but did not significantly influence the gut microbiota. Following a departure from the occupied space of several weeks, the skin microbiota, but not the gut microbiota, showed a significant reduction in similarity relative to the building. Overall, longitudinal observation of these dynamics enables us to dissect the influence of occupation, diet, and lifestyle factors on occupant and built environment microbial ecology.


E2F7 represses a network of oscillating cell cycle genes to control S-phase progression.
E2F transcription factors are known to be important for timely activation of G(1)/S and G(2)/M genes required for cell cycle progression, but transcriptional mechanisms for deactivation of cell cycle-regulated genes are unknown. Here, we show that E2F7 is highly expressed during mid to late S-phase, occupies promoters of G(1)/S-regulated genes and represses their transcription. ChIP-seq analysis revealed that E2F7 binds preferentially to genomic sites containing the TTCCCGCC motif, which closely resembles the E2F consensus site. We identified 89 target genes that carry E2F7 binding sites close to the transcriptional start site and that are directly repressed by short-term induction of E2F7. Most of these target genes are known to be activated by E2Fs and are involved in DNA replication, metabolism and DNA repair. Importantly, induction of E2F7 during G(0)-G(1)/S resulted in S-phase arrest and DNA damage, whereas expression of E2F7 during G(2)/M failed to disturb cell cycle progression. These findings provide strong evidence that E2F7 directly controls the downswing of oscillating G(1)/S genes during S-phase progression.


Beyond primary prevention of alcohol use: a culturally specific secondary prevention program for Mexican heritage adolescents.
Classroom-based primary prevention programs with adolescents are effective in inhibiting the onset of drug use, but these programs are not designed to directly address the unique needs of adolescents at higher risk of use or already using alcohol and other drugs. This article describes the initial efficacy evaluation of a companion psychosocial small group program which aims at addressing the needs of Mexican heritage students identified by their teachers as being at higher risk for substance use or already experimenting with alcohol and other drugs. The adolescent (7th grade) small group curricula, REAL Groups, is a secondary prevention program which supplements the primary classroom-based substance use prevention program, keepin' it REAL. Following a mutual aid approach, a total of 109 7th grade students were referred by their teachers and participated in the REAL Groups. The remaining 252 7th grade students who did not participate served as the control group. To account for biased selection into REAL Groups, propensity score matching (PSM) was employed. The estimated average treatment effect for participants' use of alcohol was calculated at the end of the 8th grade. Results indicate that alcohol use decreased among students who participated in the REAL Groups relative to matched students who did not participate. These findings suggest that REAL Groups may be an effective secondary prevention program for higher-risk Mexican heritage adolescents.


Cancer biology and cancer cures: reflections of a clinical investigator: presidential address.
Basic biological principles in cancer biology can be learned from laboratory experiments as well as the clinic. The clinical investigator may be able to uncover cancer biology and clinical cures, an exciting possibility. Clinical trials can and should be designed to discover biological principles as well as to test one option of surgery or drug combination versus another. During the past 20 years, a variety of clinical research programs in patients with myeloma, chronic myelogenous leukemia, lymphoma, and breast cancer have led to the discovery of important biological principles. These include contributions leading to the origin of myeloid and lymphoid cells in the marrow, the discovery of immunoglobulin D myeloma, the development of effective combination chemotherapy in Hodgkin's disease, and the concept of adjuvant therapy in breast cancer. These studies also have led to improved or new therapy for these diseases. Future research and cancer cures will undoubtedly be facilitated by close collaboration between the clinical and the laboratory investigator.


Correlating structure with non-linear optical properties in xAs40Se60·(1-x)As40S60 glasses.
A series of xAs40Se60·(100 - x)As40S60 glasses, where x = 0, 25, 33, 50, 67, 75 and 100 mol% As40Se60, has been studied using neutron and X-ray total scattering, Raman spectroscopy and (77)Se MAS-NMR. The results are presented with measurements of non-linear refractive indices, n2, and densities. There is no evidence for the formation of homopolar bonds in these glasses, but neutron correlation functions suggest that there is a non-random distribution of sulfur and selenium atoms in sulfur-rich glasses. The average number of sulfur atoms at a distance of 3-4 Å from a selenium atom, nSeS, deviates from a linear variation with x in glasses containing <50 mol% As40Se60; n2 for these glasses also varies non-linearly with x. Importantly, a direct comparison of n2 and nSeS gives a linear correlation, suggesting that n2 may be related to the distribution of chalcogen atoms in the glasses.


Mesenchymal stem cell conditioned medium increases glial reactivity and decreases neuronal survival in spinal cord slice cultures.
Ex vivo spinal cord slice cultures (SCSC) allow study of spinal cord circuitry, maintaining stimuli responses comparable to live animals. Previously, we have shown that mesenchymal stem/stromal cell (MSC) transplantation in vivo reduced inflammation and increased nerve regeneration but MSC survival was short-lived, highlighting that beneficial action may derive from the secretome. Previous in vitro studies of MSC conditioned medium (CM) have also shown increased neuronal growth. In this study, murine SCSC were cultured in canine MSC CM (harvested from the adipose tissue of excised inguinal fat) and cell phenotypes analysed via immunohistochemistry and confocal microscopy. SCSC in MSC CM displayed enhanced viability after propidium iodide staining. GFAP immunoreactivity was significantly increased in SCSC in MSC CM compared to controls, but with no change in proteoglycan (NG2) immunoreactivity. In contrast, culture in MSC CM significantly decreased the prevalence of βIII-tubulin immunoreactive neurites, whilst Ca2+ transients per cell were significantly increased. These ex vivo results contradict previous in vitro and in vivo reports of how MSC and their secretome may affect the microenvironment of the spinal cord after injury and highlight the importance of a careful comparison of the different experimental conditions used to assess the potential of cell therapies for the treatment of spinal cord injury.


Impact of Genetic Variation on Stress-Related Ethanol Consumption.
The effect of stress on alcohol consumption in humans is highly variable, and the underlying processes are not yet understood. Attempts to model a positive relationship between stress and increased ethanol (EtOH) consumption in animals have been only modestly successful. Our hypothesis is that individual differences in stress effects on EtOH consumption are mediated by genetics. We measured alcohol consumption, using the drinking-in-the-dark (DID) paradigm in females from 2 inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), and 35 of their inbred progeny (the BXD family). A control group was maintained in normal housing and a stress group was exposed to chronic mild stress (CMS), consisting of unpredictable stressors over 7 weeks. These included predator, social, and environmental perturbations. Alcohol intake was measured over 16 weeks in both groups during baseline (preceding 5-week period), CMS (intervening 7-week period), and post-CMS (final 4-week period). We detected a strong effect of CMS on alcohol intake. A few strains demonstrated CMS-related increased alcohol consumption; however, most showed decreased intake. We identified 1 nearly significant quantitative trait locus on chromosome 5 that contains the neuronal nitric oxide synthase gene (Nos1). The expression of Nos1 is frequently changed following alcohol exposure, and variants in this gene segregating among the BXD population may modulate alcohol intake in response to stress. The results we present here represent the first study to combine chronic stress and alcohol consumption in a genetic reference population of mice. Differences in susceptibility to the effects of stressful environments vis-à-vis alcohol use disorders would suggest that the differences have at least some basis in genetic constitution. We have also nominated a likely candidate gene underlying the large individual differences in effects of stress on alcohol consumption.


Knots and random walks in vibrated granular chains.
We study experimentally statistical properties of the opening times of knots in vertically vibrated granular chains. Our measurements are in good qualitative and quantitative agreement with a theoretical model involving three random walks interacting via hard-core exclusion in one spatial dimension. In particular, the knot survival probability follows a universal scaling function which is independent of the chain length, with a corresponding diffusive characteristic time scale. Both the large-exit-time and the small-exit-time tails of the distribution are suppressed exponentially, and the corresponding decay coefficients are in excellent agreement with theoretical values.


Preliminary studies on antipyretic and analgesic properties of Taverniera abyssinica.
In an attempt to ascertain the pharmacological basis of the use of the marketed traditional drug Taverniera abyssinica A. Rich. (Amharic name Dingetegna), crude extracts as well as purified substances of this plant were tested for their antipyretic and analgesic properties. Antipyretic activity was determined on rats made hyperthermic by yeast injection and analgesic activity was determined by the hot plate, as well as the acetic acid induced writhing, methods. The study showed that the plant possesses significant antipyretic and analgesic activities.


Tibial pilon fractures: a comparison of treatment methods.
This retrospective review of surgically treated distal tibia fractures was undertaken to determine whether treatment with open reduction and internal fixation (ORIF) was more efficacious in achieving fracture union than one of two external fixation methods. Of the 60 study patients with pilon fractures, 21 patients were treated with an ankle-spanning half-pin external fixator, 15 patients with a single-ring hybrid external fixator, and 24 patients with ORIF. The severity of injuries was similar across groups. There was no significant difference in complication rates between groups, although two below-knee amputations were required in the ORIF group. A greater (p = 0.03) number of malunions occurred in the fractures treated with external fixation when compared with those treated with ORIF. Fractures in the external fixator groups showed this significant tendency to lose their initial adequate reduction, independent of bone grafting or fibula fixation. There was no significant difference between groups in the need for bone grafting. There was a trend for patients treated with a single ring hybrid frame to require late bone grafting for metaphyseal-diaphyseal nonunion. External fixation offers advantages in the treatment of the soft-tissue injury associated with pilon fractures, but malunion continues to be a problem with this method of fixation.


Poly(alkyl glycidyl ether) hydrogels for harnessing the bioactivity of engineered microbes.
Herein, we describe a method to produce yeast-laden hydrogel inks for the direct-write 3D printing of cuboidal lattices for immobilized whole-cell catalysis. A poly(alkyl glycidyl ether)-based triblock copolymer was designed to have three important features for this application: (1) a temperature response, which allowed for facile processing of the material; (2) a shear response, which facilitated the extrusion of the material through a nozzle; and (3) UV light induced polymerization, which enabled the post-extrusion chemical crosslinking of network chains, and the fabrication of robust printed objects. These three key stimuli responses were confirmed via rheometrical characterization. A genetically-engineered yeast strain with an upregulated α-factor production pathway was incorporated into the hydrogel ink and 3D printed. The immobilized yeast cells exhibited adequate viability of 87.5% within the hydrogel. The production of the upregulated α-factor was detected using a detecting yeast strain and quantified at 268 nM (s = 34.6 nM) over 72 h. The reusability of these bioreactors was demonstrated via immersion of the yeast-laden hydrogel lattice in fresh SC media and confirmed by the detection of similar amounts of upregulated α-factor at 259 nM (s = 45.1 nM). These yeast-laden materials represent an attractive opportunity for whole-cell catalysis of other high-value products in a sustainable and continuous manner.


New perspectives on the use of niacin in the treatment of lipid disorders.
Therapy with niacin (nicotinic acid) is unique in that it improves all lipoprotein abnormalities. It significantly reduces low-density lipoprotein cholesterol, triglyceride, and lipoprotein(a) levels, while increasing high-density lipoprotein cholesterol levels. This makes niacin ideal for treating a wide variety of lipid disorders, including the metabolic syndrome, diabetes mellitus, isolated low high-density lipoprotein cholesterol, and hypertriglyceridemia. Niacin-induced changes in serum lipid levels produce significant improvements in both coronary artery disease and clinical outcomes. Niacin is currently available in 3 formulations (immediate release, extended release, and long acting), which differ significantly with respect to their safety and efficacy profiles. Immediate-release niacin is generally taken 3 times a day and is associated with adverse flushing, gastrointestinal symptoms, and elevations in blood glucose levels. Long-acting niacin can be taken once daily and is associated with significantly reduced flushing, but its metabolism increases the risk of hepatotoxic effects. Extended-release niacin, also given once daily, has an absorption rate intermediate between the other formulations and is associated with fewer flushing and gastrointestinal symptoms without increasing hepatotoxic risk.


Assessment of cognitive insight: a qualitative review.
The concept of cognitive insight was introduced in 2004 to describe the capacity of patients with psychosis to distance themselves from their psychotic experiences, reflect on them, and respond to corrective feedback. The Beck Cognitive Insight Scale (BCIS) was developed to evaluate these aspects of cognitive flexibility and to complement scales that describe the lack of awareness of mental illness and its characteristics. The BCIS has generated a moderate research literature, which is the subject of the current review. Several independent groups have demonstrated that the BCIS is reliable, demonstrates convergent and construct validity, and distinguishes patients with psychosis from healthy controls and patients without psychosis. While the majority of the studies have focused on the relationship of the BCIS to delusions, several have examined its relationship to negative symptoms, depression, anxiety, and functional outcome. Cognitive insight has predicted positive gains in psychotherapy of psychosis, and improvement in cognitive insight has been correlated with improvement in delusional beliefs. Finally, preliminary findings relate neurocognition, metacognition, and social cognition, as well as reduced hippocampal volume to cognitive insight. A heuristic framework is presented to guide future research.


Functions of transforming growth factor-beta family type I receptors and Smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes.
We investigated the effects of bone morphogenetic protein (BMP)-2, a member of the transforming growth factor-beta superfamily, on the regulation of the chondrocyte phenotype, and we identified signaling molecules involved in this regulation. BMP-2 triggers three concomitant responses in mouse primary chondrocytes and chondrocytic MC615 cells. First, BMP-2 stimulates expression or synthesis of type II collagen. Second, BMP-2 induces expression of molecular markers characteristic of pre- and hypertrophic chondrocytes, such as Indian hedgehog, parathyroid hormone/parathyroid hormone-related peptide receptor, type X collagen, and alkaline phosphatase. Third, BMP-2 induces osteocalcin expression, a specific trait of osteoblasts. Constitutively active forms of transforming growth factor-beta family type I receptors and Smad proteins were overexpressed to address their role in this process. Activin receptor-like kinase (ALK)-1, ALK-2, ALK-3, and ALK-6 were able to reproduce the hypertrophic maturation of chondrocytes induced by BMP-2. In addition, ALK-2 mimicked further the osteoblastic differentiation of chondrocytes induced by BMP-2. In the presence of BMP-2, Smad1, Smad5, and Smad8 potentiated the hypertrophic maturation of chondrocytes, but failed to induce osteocalcin expression. Smad6 and Smad7 impaired chondrocytic expression and osteoblastic differentiation induced by BMP-2. Thus, our results indicate that Smad-mediated pathways are essential for the regulation of the different steps of chondrocyte and osteoblast differentiation and suggest that additional Smad-independent pathways might be activated by ALK-2.


Alternative slaughter procedures: on-farm slaughter and transport system for broilers.
This paper focuses on "alternative methods for initial broiler processing" and exploration of alternative processing including slaughter at the farm immediately after catching. On-farm slaughter and transport (FSaT) is envisioned as a mobile unit that stuns, slaughters, and shackles the broiler carcasses at the farm. A separate trailer-unit then transports the shackled broiler carcasses to the processing plant. Once at the processing plant carcasses are mechanically transferred into plant shackle lines and moved into processing. The hypothesis is that the FSaT approach will dramatically improve overall bird welfare and well-being by reducing live handling and eliminating live transport from the farm to the processing plant. In addition, ancillary impacts could include: improving yield efficiencies by eliminating dead on arrivals, potentially reducing water and energy consumption, reducing labor requirements at the processing plant with the elimination of live rehang, and offering an economically sustainable alternative. The FSaT approach represents a radical change from traditional processing, and its effects on poultry processing need to be evaluated. This paper presents results of experiments conducted at a commercial poultry processor to evaluate feather picking efficiency, carcass bacteriological loading, and meat quality for delayed processed carcasses.


Altered Glia-Neuron Communication in Alzheimer's Disease Affects WNT, p53, and NFkB Signaling Determined by snRNA-seq.
Alzheimer's disease is the most common cause of dementia and is characterized by amyloid-β plaques, tau neurofibrillary tangles, and neuronal loss. Although neuronal loss is a primary hallmark of Alzheimer's disease, it is known that non-neuronal cell populations are ultimately responsible for maintaining brain homeostasis and neuronal health through neuron-glia and glial cell crosstalk. Many signaling pathways have been proposed to be dysregulated in Alzheimer's disease, including WNT, TGFβ, p53, mTOR, NFkB, and Pi3k/Akt signaling. Here, we predict altered cell-cell communication between glia and neurons. Using public snRNA-sequencing data generated from postmortem human prefrontal cortex, we predicted altered cell-cell communication between glia (astrocytes, microglia, oligodendrocytes, and oligodendrocyte progenitor cells) and neurons (excitatory and inhibitory). We confirmed interactions in an independent orthogonal dataset. We determined cell-type-specificity using Jaccard Similarity Index and investigated the downstream effects of altered interactions in inhibitory neurons through gene expression and transcription factor activity analyses of signaling mediators. Finally, we determined changes in pathway activity in inhibitory neurons. Cell-cell communication between glia and neurons is altered in Alzheimer's disease in a cell-type-specific manner. As expected, ligands are more cell-type-specific than receptors and targets. We validated 51 ligand- receptor pairs in an independent dataset that included two known Alzheimer's disease risk genes: APP and APOE . 17 (14 upregulated and 3 downregulated in Alzheimer's disease) of the 51 interactions also had the same downstream target gene. Most of the signaling mediators of these interactions were not differentially expressed, however, the mediators that are also transcription factors had differential activity between AD and control. Namely, MYC and TP53 , which are associated with WNT and p53 signaling, respectively, had repressor activity in Alzheimer's disease, along with decreased WNT and p53 activity in inhibitory neurons. Additionally, inhibitory neurons had both increased NFkB signaling pathway activity and activator activity of NFIL3 , an NFkB signaling-associated transcription factor. Cell-cell communication between glia and neurons in Alzheimer's disease is altered in a cell-type-specific manner involving Alzheimer's disease risk genes. Signaling mediators had altered transcription factor activity suggesting altered glia-neuron interactions may dysregulate signaling pathways including WNT, p53, and NFkB in inhibitory neurons.


Imidazolium-Containing Hybrid Organic-Inorganic Materials for the Conversion of CO2: Unveiling the Key Role of the Ionic Template.
A straightforward synthesis of a series of hybrid organic-inorganic materials (HOIMs) containing imidazolium moieties was achieved. The preparation of the imidazolium acetate precursor was performed in a single-step procedure using the Debus-Radziszewski reaction. The as-synthesized alkoxysilane was employed in combination with tetraethyl orthosilicate to generate an HOIM presenting a high specific surface area. Two different structure-directing agents (SDAs), an anionic (sodium dodecyl sulfate (SDS)) or a cationic (cetyltrimethylammonium bromide) surfactant, were used to investigate the role played by the SDA on the distribution of the imidazolium-based active sites within the silica structure. After the synthesis, the acetate ion was replaced with Cl- and Br- via a simple acid treatment. This procedure favors also the removal of the surfactant, thus releasing the porosity of the solids. The HOIMs synthesized were fully characterized via low-angle X-ray diffraction, N2 physisorption, transmission electron microscopy, 13C and 29Si MAS NMR, combustion chemical analysis, X-ray photoelectron spectroscopy, and CO2 physisorption to assess their physicochemical and structural features, as well as the successful incorporation of imidazolium salts. Their catalytic activity in the conversion of CO2 was tested over different epoxides to produce the corresponding cyclic carbonates. The key role of the SDS (anionic surfactant) as a templating agent was proved. The best material was stable under the selected reaction conditions, reusable over multiple cycles, and active on a series of different epoxides, thus proving its versatility.


Metamicrobiomics in herbivore beetles of the genus Cryptocephalus (Chrysomelidae): toward the understanding of ecological determinants in insect symbiosis.
The Cryptocephalus marginellus (Coleoptera: Chrysomelidae) complex is composed by six species that are supposed to have originated by events of allo- or parapatric speciation. In the present study we investigated the alternative hypotheses that the bacterial communities associated with six populations of this species complex are shaped by environmental factors, or reflect the proposed pattern of speciation. The microbiota associated with the six populations, from five species of the complex, have been characterized through 16S rRNA pyrotag sequencing. Based on a 97% sequence similarity threshold, data were clustered into 381 OTUs, which were analyzed using a variety of diversity indices. The microbiota of C. acquitanus and C. marginellus (Calanques) were the most diverse (over 100 OTUs), while that from C. zoiai yielded less bacterial diversity (45 OTUs). Taxonomic assignment revealed Proteobacteria, Tenericutes and Firmicutes as the dominant components of these beetles' microbiota. The most abundant genera were Ralstonia, Sphingomonas, Rickettsia, and Pseudomonas. Different strains of Rickettsia were detected in C. eridani and C. renatae. The analysis of β-diversity revealed high OTU turnover among the populations of C. marginellus complex, with only few shared species. Hierarchical clustering taking into account relative abundances of OTUs does not match the phylogeny of the beetles, therefore we hypothesize that factors other than phylogenetic constraints play a role in shaping the insects' microbiota. Environmental factors that could potentially affect the composition of bacterial communities were tested by fitting them on the results of a multi-dimensional scaling analysis. No significant correlations were observed towards the geographic distances or the host plants, while the composition of the microbiota appeared associated with altitude. The metabolic profiles of the microbiotas associated with each population were inferred from bacterial taxonomy, and interestingly, the obtained clustering pattern was consistent with the host phylogeny.


The interconversion of diacylglycerol and phosphatidylcholine during triacylglycerol production in microsomal preparations of developing cotyledons of safflower (Carthamus tinctorius L.).
Microsomal preparations from the developing cotyledons of safflower (Carthamus tinctorius) catalyse the acylation of sn-glycerol 3-phosphate in the presence of acyl-CoA. Under these conditions the radioactive glycerol in sn-glycerol 3-phosphate accumulates in phosphatidic acid, phosphatidylcholine, diacyl- and tri-acylglycerol. The incorporation of glycerol into phosphatidylcholine is via diacylglycerol and probably involves a cholinephosphotransferase. The results show that the glycerol moiety and the acyl components in phosphatidylcholine exchange with the diacylglycerol during the biosynthesis of diacylglycerol from phosphatidic acid. The continuous reversible transfer of diacylglycerol with phosphatidylcholine, which operates during active triacylglycerol synthesis, will control in part the polyunsaturated-fatty-acid quality of the final seed oil.


Early Complication of Humeral Derotational Osteotomy Surgery for Obstetric Brachial Plexus as Salvage for a Failed Tendon Transfer. Case Report.
In brachial plexus injuries, external rotation in patients with a moderate to severe glenohumeral dysplasia is corrected with derotational humeral osteotomy surgery. The most frequent complications described for this procedure include keloid scar, loss of external rotation secondary to bone remodelling, loss of internal rotation, prominence of osteosynthesis, fracture distal to the plate transient ulnar paraesthesia and radial nerve palsy (1), and delayed union and non-union. Rarely, treating complications associated with derotational humeral osteotomy may require revision of osteosynthesis (2). The literature that investigates the effectiveness of derotational humeral osteotomy as a procedure to rescue dorsal infraspinatus tendon transfer is limited. This article is the first communication of a pediatric patient with an obstetric brachial plexus injury receiving a derotational osteotomy as a procedure to salvage a failed rescue Latissimus dorsi tendon transfer with a complication. This case report was performed according to the principles of the Declaration of Helsinki. Written informed consent for participation in this case report was obtained from the patient's parents.


Population study about the attitude toward organ xenotransplantation in the population from Eastern Europe resident in southeast Spain.
The objective of this paper is to analyze the attitude toward xenotransplantation and to determine the variables that influence this attitude in the population of southeast Spain who were born in Eastern European countries. A random sample was taken of natives from Eastern Europe residing in southeast Spain (n=320). The sample was obtained randomly between November 2005 and April 2006 and stratified according to the respondents' nationality. Attitude was evaluated using a validated questionnaire which was self-administered and completed anonymously. The control group was a random sample of the native Spanish population (n=250). The statistical analysis used included Student's t-test, the chi-square test, Fisher's exact test, and a logistic regression analysis. The questionnaire completion rate was 83% (n=267). Regarding the use of animal organs for transplantation in humans, if the outcome were similar to that achieved when using human organs, 43% (n=114) would be in favor, 32% (n=86) undecided, and the remaining 25% (n=67) would be against it. This attitude is less favorable than in the control group (43% versus 74%, p<0.001). The attitude was related to the following factors: 1) the country of origin (p<0.001); 2) participation in social help activities (p<0.001); 3) discussion on organ donation and transplantation within the family (p=0.005); 4) previous experience of organ donation and transplantation (p=0.002); 5) the respondent's religion (p=0.002); 6) knowing that one's partner had a favorable attitude toward transplantation (p<0.001); 7) the respondent's belief that he or she might need a transplant in the future (p<0.001); 8) the attitude toward human donation, both from cadaver (p<0.001) and living (p<0.001) donors. The following were also independent variables in the subsequent multivariate analysis: 1) favorable attitude toward cadaver organ donation (OR=4.998); 2) previous experience of donation (0R=2.857); 3) partner's attitude against transplantation (OR=0.079); and 4) attitude toward living donation (OR=12. 703). The attitude toward xenotransplantation is less positive among Eastern Europeans living in Spain than in the native Spanish population and is influenced by many psychosocial factors that are mainly related to human organ donation.


Thyrotropin increases prostaglandin levels in isolated thyroid cells.
We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.


Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation.
We aimed to find crucial microRNAs (miRNAs) associated with the development of atrial fibrillation (AF), and then try to elucidate the possible molecular mechanisms of miRNAs in AF. The miRNA microarray, GSE68475, which included 10 right atrial appendage samples from patients with persistent AF and 11 samples from patients with normal sinus rhythm, was used for the analysis. After data preprocessing, differentially expressed miRNAs were screened using limma. Target genes of miRNAs were predicted using miRWalk2.0. We then conducted functional enrichment analyses for miRNA and target genes. Protein-protein interaction (PPI) network and module analyses for target genes were performed. Finally, transcription factors (TFs)-target genes regulatory network was predicted and constructed. Seven genes, including CAMK2D, IGF2R, PPP2R2A, PAX6, POU3F2, YWHAE, and AP2A2, were targeted by TFs. Among these seven genes, CAMK2D (targeted by miR-31-5p), IGF2R (targeted by miR-204-5p), PAX6 (targeted by miR-223-3p), POU3F2 (targeted by miR-204-5p), YWHAE (targeted by miR-31-5p), and AP2A2 (targeted by miR-204-5p) belonged to the top 10 degree genes in the PPI network. Notably, MiR-204-5p, miR-31-5p, and miR-223-3p had more target genes. Besides, CAMK2D was enriched in some pathways, such as adrenergic signaling in cardiomyocytes pathway and cAMP signaling pathway. YWHAE was enriched in the Hippo signaling pathway. miR-31-5p played a crucial role in cardiomyocytes by targeting CAMK2D and YWHAE via cAMP and Hippo signaling pathways. miR-204 was involved in the progression of AF by regulating its target genes IGF2R, POU3F2, and AP2A2. On the other hand, miR-223-3p functioned in AF by targeting PAX6, which was associated with the regulation of apoptosis in AF. This study would provide a theoretical basis and potential therapeutic targets for the treatment of AF. (Anatol J Cardiol 2020; 23: 324-33).


Brain Networks Underlying Eye's Pupil Dynamics.
Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.


Multiframe error concealment for MPEG-coded video delivery over error-prone networks.
Compressed video sequences are very vulnerable to channel disturbances when they are transmitted through an unreliable medium such as a wireless channel. Transmission errors not only corrupt the current decoded frame, but they may also propagate to succeeding frames. A number of post-processing error concealment (ECN) methods that exploit the spatial and/or temporal redundancy in the video signal have been proposed to combat channel disturbances. Although these approaches can effectively conceal lost or erroneous macroblocks (MBs), all of them only consider spatial and/or temporal correlation in a single frame (the corrupted one), which limits their ability to obtain an optimal recovery. Since the error propagates to the next few motion-compensated frames in the presence of lost MBs in an I or P frame, error concealment should simultaneously minimize the errors not only in the current decoded frame but also in the succeeding B and P frames that depend on the corrupted frame. We propose a novel multiframe recovery principle which analyzes the propagation of a lost MB into succeeding frames. Then, MPEG-compatible spatial and temporal error concealment approaches using this multiframe recovery principle are proposed, where the lost MBs are recovered in such a way that the error propagation is minimized.


Mixed neuropathology in frontotemporal lobar degeneration.
Aim: Frontotemporal lobar degeneration (FTLD) is a significant cause of dementia in mid-life and older adults. The extent of interactions between FTLD and other neurodegenerative pathologies is unclear. We reviewed the occurrences of mixed pathology in cases of neuropathologically diagnosed FTLD from the UK Brain Bank Network. Materials and methods: Clinicopathological details of cases of FTLD were extracted from the UK Brain Bank Network database. Results: Of 515 cases, 30.10% had mixed neuropathology. Concordance between clinical and neuropathological diagnosis was lower in these cases (38.71% vs. 59.17%). Alzheimer's spectrum pathology was the commonest additional finding. Age at death was higher in mixed neuropathology cases (mean 76.7 years vs. 72.59.0 years, p < 0.005), increasing in tandem with the number of neuropathologies present. Conclusion: Mixed neuropathology is common in FTLD and associated with increased age at death. Our findings suggest that mixed neuropathology influences age at onset and clinical phenotype in FTLD and makes accurate antemortem diagnosis more difficult. Further investigation of interactions between neuropathologies and phenotype is warranted, particularly in view of the potential impact on clinical diagnosis and patient selection for clinical trials.Key pointsMixed neurodegenerative neuropathologies commonly occur with frontotemporal lobar degeneration.The likelihood of mixed neuropathology with FTLD increases with older age at death.Mixed neuropathology could influence the clinical phenotype of frontotemporal lobar degeneration.


Does mechanical massage of the abdominal wall after colectomy reduce postoperative pain and shorten the duration of ileus? Results of a randomized study.
The aim of this study was to determine the effectiveness of mechanical abdominal massage on postoperative pain and ileus after colectomy. We hypothesized that parietal abdominal stimulation could counteract induced pain and postoperative ileus, through common spinal-sensitive pathways, with nociceptive visceral messages. After preoperative randomization, 25 patients (age 52 +/- 5 years) underwent active mechanical massage by intermittent negative pressure on the abdominal wall resulting in aspiration (Cellu M50 device, LPG, Valence, France), and 25 patients (age 60 +/- 6 years) did not receive active mechanical massage (placebo group). Massage sessions began the first day after colectomy and were performed daily until the seventh postoperative day. In the active-massage group, amplitude and frequency were used, which have been shown to be effective in reducing muscular pain, whereas in the placebo group, ineffective parameters were used. Visual analogue scale (VAS) pain scores, doses of analgesics (propacetamol), and delay between surgery and the time to first passage of flatus were assessed. Types and dosages of the anesthetic drugs and the duration of the surgical procedure did not differ between groups. From the second and third postoperative days, respectively, VAS pain scores (P < 0.001) and doses of analgesics (P < 0.05) were significantly lower in patients receiving active massage compared to the placebo group. Time to first passage of flatus was also significantly shorter in the active-massage group (1.8 +/- 0.3 days vs. 3.6 +/- 0.4 days, P < 0.01). No adverse effects were observed. These results suggest that mechanical massage of the abdominal wall may decrease postoperative pain and ileus after colectomy.


Chlordecone exposure, length of gestation, and risk of preterm birth.
Persistent organic pollutants have not been conclusively associated with length of gestation or with preterm birth. Chlordecone is an organochlorine pesticide that has been extensively used to control the banana root borer population in the French West Indies. Data from the Timoun Mother-Child Cohort Study conducted in Guadeloupe between 2004 and 2007 were used to examine the associations of chlordecone concentrations in maternal plasma with the length of gestation and the rate preterm birth in 818 pregnant women. Data were analyzed using multivariate linear regression for length of gestation and a Cox model for preterm birth. The median plasma chlordecone concentration was 0.39 µg/L (interquartile range, 0.18-0.83). No correlation was observed with plasma concentrations of p,p'-dichlorodiphenyl dichloroethene (ρ = 0.017) or polychlorinated biphenyl 153 (ρ = -0.016), the other main organochlorine compounds detected. A 1-log10 increase in chlordecone concentration was associated with a decreased length of gestation (-0.27 weeks; 95% confidence interval: -0.50, -0.03) and an increased risk of preterm birth (60%; 95% confidence interval: 10, 130). These associations may result from the estrogen-like and progestin-like properties of chlordecone. These results are of public health relevance because of the prolonged persistence of chlordecone in the environment and the high background rate of preterm births in this population.


Diagnostic Agreement between Prehospital Emergency and In-Hospital Physicians.
The aim of the study was to determine the diagnostic agreement between the discharge diagnosis and the suspected diagnosis by the prehospital emergency physician and to run a sensitivity analysis of the most common diagnoses by the prehospital emergency physician. The diagnostic agreement was determined by a systematic comparison of the discharge diagnosis with suspected diagnosis by the prehospital emergency physician in a period of 24 months at the emergency medical services in Bad Belzig. The diagnostic agreement of the 13 most common discharge diagnoses was compared to the remaining diagnostic agreement. The results were tested for statistical significance using the chi-squared test. In 64.1% of cases included, a diagnostic agreement occurred. There was a high proportion of diagnostic agreement for hypoglycemia (97%), atrial fibrillation (87%), cramping seizure (86%), hypertensive crisis (85.5%), and syncope (81%). There was a low proportion of diagnostic agreement for chest wall pain (27%), pneumonia (32%), and cardiac decompensation (53%). Our attention in practice and emergency medical courses should be directed to chest pain patients and the main symptom of dyspnea, because of the high proportion of incorrect diagnoses by the prehospital emergency physician. It should be noted that 92% of incorrectly diagnosed chest wall pain cases were overestimated with an acute coronary syndrome.


Human phosphoribosylformylglycineamide amidotransferase (FGARAT): regional mapping, complete coding sequence, isolation of a functional genomic clone, and DNA sequence analysis.
Purines play essential roles in many cellular functions, including DNA replication, transcription, intra- and extra-cellular signaling, energy metabolism, and as coenzymes for many biochemical reactions. The de-novo synthesis of purines requires 10 enzymatic steps for the production of inosine monophosphate (IMP). Defects in purine metabolism are associated with human diseases. Further, many anticancer agents function as inhibitors of the de-novo biosynthetic pathway. Genes or cDNAs for most of the enzymes comprising this pathway have been isolated from humans or other mammals. One notable exception is the phosphoribosylformylglycineamide amidotransferase (FGARAT) gene, which encodes the fourth step of this pathway. This gene has been cloned from numerous microorganisms and from Drosophila melanogaster and C. elegans. We report here the identification of a human cDNA containing the coding region of the FGARAT mRNA and the isolation of a P1 clone that contains an intact human FGARAT gene. The P1 clone corrects the purine auxotrophy and protein deficiency of Chinese hamster ovary (CHO) cell mutants (AdeB) deficient in both the activity and the protein for FGARAT. The P1 clone was used to regionally map the FGARAT gene to chromosome region 17p13, a location consistent with our prior assignment of this gene to chromosome 17. A comparison of the DNA sequence of the human FGARAT and FGARAT DNA sequence from 17 other organisms is reported. The isolation of this gene means that DNA clones for all the 10 steps of IMP synthesis have been isolated from humans or other mammals.


Detection of a homologue of bcl-2 in plant cells.
An emerging family of bcl-2-like genes has been identified from nematode to humans. These genes play a role in the maintenance of homeostasis. Its members have highly conserved domains that are important for their dimerization. Since nothing is known about the importance of these genes in plant cells, we have investigated their presence in an alga as well as in three higher plants both by Western analysis and by immunocytochemistry. Immunoblots revealed the presence of a protein immunoreacting with the anti-bcl-2 polyclonal antibody in leaves of tobacco plants. Furthermore, immunocytochemical localization has shown that this protein is mainly associated with mitochondria, plastids, and nuclei of plant cells. Taken together, our results suggest that bcl-2 is a protein highly conserved throughout evolution.


Carcinoma in situ of the vagina. A study and review.
A retrospective study has been carried out on 25 patients treated at the University of Michigan Medical Center for carcinoma in situ of the vagina. Intraepithelial carcinoma of the vagina occurred as a primary entity, following treatment for preinvasive and invasive carcinoma of the cervix, and following hysterectomy for benign disease of the uterus. These patients were treated with either radium implantation or some form of surgery. Five patients had recurrences. These 5 were all subsequently retreated and are alive and without evidence of further recurrent neoplasm. This series of carcinoma in situ of the vagina is compared to other reported series. Emphasis is directed toward the need for continued use of Papanicolaou smear cytology tests in posthysterectomy patients, regardless of the reason for hysterectomy.


Metabolic effects of dietary fiber from dehulled soybeans in humans.
The normal diet of six healthy volunteers was supplemented by 21 g of dietary fiber from two different soybean seed fiber preparations, either a nonpurified and never-dried soya pulp A (39% dietary fiber) or a purified soya fiber B (79%), for 3 wk each. Mean daily fecal wet weight was increased by 19 and 38% in the fiber periods A and B as compared to a 2-wk control period (p less than 0.05). Stool frequency and transit time remained unchanged. Fecal fiber increased by 52% only during period B. Fecal calcium, magnesium, and iron were increased (p less than 0.05), mainly after higher intakes during both fiber periods. Excretion of neutral steroids remained unchanged, but their concentration was lowered (p less than 0.05). A 21% increase of fecal bile acids by fiber A was specifically due to deoxycholic acid (+32%, p less than 0.01). Oral glucose tolerance was slightly improved after period B. Neither fiber changed serum triglycerides, but fiber B increased low-density lipoprotein-cholesterol by 19% (p less than 0.01) and low-density lipoprotein-phospholipids by 16% (p less than 0.05). The ratio high-density/low-density lipoprotein-cholesterol, however, did not change significantly. Thus, dietary fibers from soybean do not seem to contribute to the hypocholesterolemic effect of soya. The results of this study also demonstrate that two apparently similar dietary fibers, coming from a single source, can exert distinctly different metabolic effects.


Multiresolution tomographic reconstruction using wavelets.
Shows how the separable two-dimensional wavelet representation leads naturally to an efficient multiresolution tomographic reconstruction algorithm. This algorithm is similar to the conventional filtered backprojection algorithm, except that the filters are now angle dependent, and the backprojection gives the wavelet coefficients of the reconstruction, which are then used to synthesize the reconstruction at various resolution levels. By reconstructing only a small localized region at high resolution, the authors show how radiation exposure and computation can be significantly reduced, compared to a standard reconstruction.


The Legionella pneumophila LidA protein: a translocated substrate of the Dot/Icm system associated with maintenance of bacterial integrity.
Legionella pneumophila establishes a replication vacuole within phagocytes that requires the bacterial Dot/Icm apparatus for its formation. This apparatus is predicted to translocate effectors into host cells. We hypothesized that some translocated proteins also function to maintain the integrity of the Dot/Icm translocator. Mutations that destroy this function are predicted to result in a Dot/Icm complex that poisons the bacterium, resulting in reduced viability. To identify such mutants, strains were isolated (called lid-) that showed reduced viability on bacteriological medium in the presence of an intact Dot/Icm apparatus, but which had high viability in the absence of the translocator. Several such mutants were analysed in detail to identify candidate strains that may have lost the ability to synthesize a translocated substrate of Dot/Icm. Two such strains had mutations in the lidA gene. The LidA protein exhibits properties expected for a translocated substrate of Dot/Icm that is important for maintenance of bacterial cell integrity: it associates with the phagosomal surface, promotes replication vacuole formation, and is important for both efficient intracellular growth and high viability on bacteriological media after introduction of a plasmid that allows high level expression of the dotA gene.


Transactional Processes Among Childhood Maltreatment, Self-Control and Aggression in Early Adolescence: Disentangling Between- and Within-Person Associations.
Previous research has investigated the associations among childhood maltreatment, self-control, and aggression among adolescents without distinguishing between-person effects from within-person effects. Thus, we evaluated the dynamic longitudinal associations among childhood maltreatment, self-control, and aggression, including whether self-control functioned as a mediator of the reciprocal relations between childhood maltreatment and aggression at the within-person level after disentangling between- and within-person associations. A sample of 2050 Chinese early adolescents (43.69% girls, Mage = 10.39 years, SD = 0.55, range = 9 to 12 years at T1) completed measures on 5 occasions across 2.5 years, using 6-month intervals. Random Intercept Cross-Lagged Panel Models were applied to disaggregate between- and within-person effects. RI-CLPMs analysis revealed that at the within-person level: (a) Childhood maltreatment and aggression bidirectionally predicted each other; (b) Childhood maltreatment and self-control bidirectionally predicted each other; (c) Aggression predicted subsequent self-control but not vice versa; (d) Childhood maltreatment did not indirectly predict aggression via self-control and vice versa; (e) Additionally, there were no gender differences observed in the longitudinal associations among childhood maltreatment, self-control and aggression. These findings advanced the literature by elucidating longitudinal associations among childhood maltreatment, self-control, and aggression at the within-person level, highlighting the significance of distinguishing between- and within-person effects in research informing the development of prevention and intervention programs aimed at reducing adolescent aggression.


Alkyne hydroarylation in ionic liquids catalyzed by palladium(II) complexes.
The efficiency of dicarbene palladium(II) complexes and of simple palladium(II) acetate as catalysts for alkyne hydroarylation under liquid-liquid biphasic conditions involving an ionic liquid as the catalyst-containing phase is investigated. The results obtained under these conditions, both in terms of activity and selectivity, are compared with those previously obtained under homogeneous conditions. The catalytic efficiency of the systems is found to be markedly dependent on the nature of the anion of the ionic liquid. Suitable anions are found to significantly improve the catalytic performance in comparison to homogeneous conditions. Preliminary investigations on the recyclability of the system as well as the on advantages of using an acidic ionic liquid are also carried out.


Changes in the epidemiological landscape of invasive mould infections and disease.
Although a wide variety of pathogens are associated with invasive mould diseases, Aspergillus spp. have historically been one of the most common causative organisms. Most invasive mould infections are caused by members of the Aspergillus fumigatus species complex and an emerging issue is the occurrence of azole resistance in A. fumigatus, with resistance to amphotericin B documented in other Aspergillus spp. The epidemiology of invasive fungal disease has shifted in recent years as non-A. fumigatus Aspergillus spp. and other moulds have become progressively more important, although there are no consolidated data on the prevalence of less common species of moulds. The incidence of mucormycosis may have been underestimated, which is a potential concern since species belonging to the order Mucorales are more resistant to antifungal agents than Aspergillus spp. All species of Mucorales are unaffected by voriconazole and most show moderate resistance in vitro to echinocandins. Fusarium spp. may be the second most common nosocomial fungal pathogen after Aspergillus in some tertiary hospitals, and show a susceptibility profile marked by a higher level of resistance than that of Aspergillus spp. Recently, Scedosporium aurantiacum has been reported as an emerging opportunistic pathogen, against which voriconazole is the most active antifungal agent. Other mould species can infect humans, although invasive fungal disease occurs less frequently. Since uncommon mould species exhibit individual susceptibility profiles and require tailored clinical management, accurate classification at species level of the aetiological agent in any invasive fungal disease should be regarded as the standard of care.


HIV incidence estimate combining HIV/AIDS surveillance, testing history information and HIV test to identify recent infections in Lazio, Italy.
The application of serological methods in HIV/AIDS routine surveillance systems to identify persons with recently acquired HIV infection has been proposed as a tool which may provide an accurate description of the current transmission patterns of HIV. Using the information about recent infection it is possible to estimate HIV incidence, according to the model proposed by Karon et al. in 2008, that accounts for the effect of testing practices on the number of persons detected as recently infected. We used data from HIV/AIDS surveillance in the period 2004-2008 to identify newly diagnosed persons. These were classified with recent/non-recent infection on the basis of an avidity index result, or laboratory evidence of recently acquired infection (i.e., previous documented negative HIV test within 6 months; or presence of HIV RNA or p24 antigen with simultaneous negative/indeterminate HIV antibody test). Multiple imputation was used to impute missing information. The incidence estimate was obtained as the number of persons detected as recently infected divided by the estimated probability of detection. Estimates were stratified by calendar year, transmission category, gender and nationality. During the period considered 3,633 new HIV diagnoses were reported to the regional surveillance system. Applying the model, we estimated that in 2004-2008 there were 5,465 new infections (95%CI: 4,538-6,461); stratifying by transmission category, the estimated number of infections was 2,599 among heterosexual contacts, 2,208 among men-who-have-sex-with-men, and 763 among injecting-drug-users. In 2008 there were 952 (625-1,229) new HIV infections (incidence of 19.9 per 100,000 person-years). In 2008, for men-who-have-sex-with-men (691 per 100,000 person-years) and injecting drug users (577 per 100,000 person-years) the incidence remained comparatively high with respect to the general population, although a decreasing pattern during 2004-2008 was observed for injecting-drug-users. These estimates suggest that the transmission of HIV infection in Lazio remains frequent and men-who-have-sex-with men and injecting-drug-users are still greatly affected although the majority of new infections occurs among heterosexual individuals.


Enantioselective Palladium(II)-Catalyzed Desymmetrizative Coupling of 7-Azabenzonorbornadienes with Alkynylanilines.
A PdII -catalyzed, domino enantioselective desymmetrizative coupling of 7-azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three covalent bonds and two contiguous stereocenters with excellent enantio- and diastereo-selectivity. The resulting functionalized indole-dihydronaphthalene-amine conjugates served as an appealing platform to streamline the diversity-oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non-covalent interactions contributed to the observed enantioselectivity.


OSCAR is a receptor for surfactant protein D that activates TNF-α release from human CCR2+ inflammatory monocytes.
Surfactant protein D (SP-D) is critical for maintenance of lung homeostasis and provides a first line of defense to pathogens at mucosal surfaces. Polymorphisms in the SP-D-encoding gene SFTPD have been associated with chronic obstructive pulmonary disease and ulcerative colitis. Identification of the immunoreceptors that bind SP-D is essential for understanding its contribution to lung homeostasis and mucosal defense. We located a putative binding motif for the osteoclast-associated receptor (OSCAR) within the SP-D collagenous domain. An OSCAR-Fc fusion protein specifically bound to the collagenous region of recombinant SP-D and captured native SP-D from human bronchoalveolar lavage. OSCAR localized in an intracellular compartment of alveolar macrophages together with SP-D. Moreover, we found OSCAR on the surface of interstitial lung and blood CCR2(+) inflammatory monocytes, which secreted TNF-α when exposed to SP-D in an OSCAR-dependent fashion. OSCAR and SP-D did not exclusively colocalize in lung, as they were also highly expressed in atherosclerotic plaques of human aorta, supporting a role for this interaction in atherosclerosis. Our results identify the OSCAR:SP-D interaction as a potential therapeutic target in chronic inflammatory diseases of the lung as well as other diseases involving tissue accumulation of SP-D, infiltration of inflammatory monocytes, and release of TNF-α.


The influence of induction therapy on graft and patient survival in patients with and without hepatitis C after liver transplantation.
We used the United Network for Organ Sharing Database to determine the influence of antibody-based induction therapy on patient and graft survival in orthotopic liver transplant (OLT) recipients with and without hepatitis C (HCV). We identified all initial OLT patients with HCV serology. Patients were divided into four groups: HCV positive without induction (17 362), HCV positive with induction (3479), HCV negative without induction (20 417) and HCV negative with induction (4357). Both HCV positive and negative patients who received induction did better than those who did not. For HCV positive patients, 5-year patient survival was 70.8% versus 68.7% (p = 0.004) and graft survival was 65.2% versus 62.1% (p < 0.001). For HCV negative patients, 5-year patient survival was 78.8% versus 76.7% (p < 0.001) and graft survival was 74.0% versus 70.8% (p < 0.001). On multivariate analysis, induction was associated with improved patient (HR = 0.91: p = 0.024) and graft (HR = 0.88: p < 0.001) survival in HCV positive patients and improved patient (HR = 0.87: p = 0.003) and graft survival (HR = 0.87: p < 0.001) in HCV negative patients. The benefit of induction occurred early and largely dissipated when patients with death within a year were censored. The benefit of induction therapy appeared most pronounced in patients with renal insufficiency or on organ-perfusion support at transplant.


Effects of glycerin on receiving performance and health status of beef steers and nutrient digestibility and rumen fermentation characteristics of growing steers.
One experiment was conducted to evaluate the influence of glycerin (GLY) on animal performance and health when used as a partial replacement for roughage in receiving diets. The second experiment was conducted using ruminally and duodenally cannulated steers in a 4 × 4 Latin square to determine the site of nutrient digestion and ruminal fermentation characteristics when GLY replaced roughage at 0%, 2.5%, 5%, and 10% of diet DM. In Exp. 1, steers (initial BW = 245 ± 2.3 kg) were fed treatment diets over a 42-d period that consisted of a control diet based on steam-flaked corn with GLY inclusion in replacement of dietary roughage at 0%, 5%, and 10% of diet DM. A linear reduction in DMI was observed as GLY increased (P = 0.01). Glycerin incorporation tended to improve G:F in a linear manner (P = 0.07); efficiency was improved 5.4% and 4.7% at 5% and 10% GLY. The number of animals receiving treatment for bovine respiratory disease did not differ among treatments. Furthermore, there were no differences among treatments for mortality or the frequency of steers that were seropositive for serum antibody titers to infectious bovine rhinotracheitis on d 28. In Exp. 2, apparent OM and apparent and true starch digestibility increased linearly (P < 0.05) as GLY concentration increased, whereas true OM digestibility responded in a quadratic (P < 0.01) manner. Bacterial OM and bacterial starch flow responded quadratically (P ≤ 0.02), and flow increased from 0% to 5% GLY inclusion and decreased thereafter. Feed OM flow responded quadratically (P ≤ 0.05), where it decreased from 0% to 2.5% GLY and increased from 2.5% to 10% GLY inclusion. Feed starch (P = 0.02) and total starch (P = 0.02) flow from the duodenum decreased linearly as the concentration of GLY increased in the diet. Bacterial N flow to the duodenum responded quadratically (P < 0.01); it increased with increasing GLY in the diet up to 5% and then decreased from 5% to 10%. The acetate to propionate (A:P) ratio in the ruminal fluid decreased (P < 0.05) as the concentration of GLY in the diet increased, which could have implications on improved G:F. The decrease in the A:P ratio as GLY increased in the diet, coupled with the linear decrease in DMI and improvement in G:F with GLY addition up to 5% of DM in place of roughage, implies that GLY is a viable dietary ingredient in growing and receiving diets.


Evaluation of the protonation thermochemistry obtained by the extended kinetic method.
An evaluation of the results obtained by the extended kinetic method for a series of representative bases is presented here. Analysis of the original experimental data is conducted using the orthogonal distance regression (ODR) statistical treatment. A comparison with the proton affinities and protonation entropies obtained from variable temperature equilibrium constant measurements demonstrate deviations, which may be ascribed to random and systematic errors. Considerable random errors are associated with the extended kinetic method if the number of reference bases and the range of effective temperatures are too low. It is also confirmed that large systematic errors on proton affinities and protonation entropies are obtained when large protonation entropy is associated with the considered system. It is, however, encouraging to note that the gas phase basicities obtained by the extended kinetic method are generally comparable to that obtained by other methods within a few kJ/mol.


The evidence-based dentistry initiative at Baylor College of Dentistry.
This report describes the impact of an R25 Oral Health Research Education Grant awarded to the Texas A&M Health Science Center-Baylor College of Dentistry (BCD) to promote the application of basic and clinical research findings to clinical training and encourage students to pursue careers in oral health research. At Baylor, the R25 grant supports a multi-pronged initiative that employs clinical research as a vehicle for acquainting both students and faculty with the tools of evidence-based dentistry (EBD). New coursework and experiences in all 4 years of the curriculum plus a variety of faculty development offerings are being used to achieve this goal. Progress on these fronts is reflected in a nascent "EBD culture" characterized by increasing participation and buy-in by students and faculty. The production of a new generation of dental graduates equipped with the EBD skill set as well as a growing nucleus of faculty who can model the importance of evidence-based practice is of paramount importance for the future of dentistry.


Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma.
To determine the diagnostic capability of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL). All human immunodeficiency virus (HIV)-infected patients with focal brain lesions observed between June 1996 and March 1998 underwent lumbar puncture and 201Tl SPECT. Each CSF sample was tested with polymerase chain reaction (PCR) for EBV-DNA. Thirty-one patients were included, 13 with PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive. Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95% confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P<.0002). Using a lesion/background ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16 nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased 201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94% negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity and 100% positive predictive value. The presence of increased uptake and/or positive EBV-DNA had 100% sensitivity and 100% NPV. Combined SPECT and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL. Because PCNSL likelihood is extremely high in patients with hyperactive lesions and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly undergo radiotherapy or multimodal therapy. On the contrary, in patients showing hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to be advisable.


Correction of Hypercortisolemia with an Improved Cognitive Function and Muscle Mass after Transsphenoidal Surgery in an Older Patient with Cushing's Disease.
Cushing's disease causes numerous metabolic disorders, cognitive decline, and sarcopenia, leading to deterioration of the general health in older individuals. Cushing's disease can be treated with transsphenoidal surgery, but thus far, surgery has often been avoided in older patients. We herein report an older woman with Cushing's disease whose cognitive impairment and sarcopenia improved after transsphenoidal surgery. Although cognitive impairment and sarcopenia in most older patients show resistance to treatment, our case indicates that normalization of the cortisol level by transsphenoidal surgery can be effective in improving the cognitive impairment and muscle mass loss caused by Cushing's disease.


Idiopathic venous thrombosis is related to systemic inflammatory response and to increased levels of circulating markers of endothelial dysfunction.
During the past decade, the role of inflammation in the pathophysiology of arterial thrombosis has been elucidated. However, little is known about the relationship between inflammation and venous thrombosis. Recently, inflammation has been accepted as a possible mechanism through which different risk factors trigger thrombus formation in veins. The aim of the present study was to investigate the inflammatory markers and their relationship to idiopathic venous thrombosis. Fourty-nine patients with first idiopathic venous thrombosis and 48 age matched control subjects were included in the study. Patients were studied 2-4 months after the acute event. Patients and control subjects did not differ in the classical risk factors of atherosclerosis, except in body mass index. In both groups, blood markers of inflammation, namely high sensitive C-reactive protein (hs CRP), interleukins (IL-6, IL-8) and tumour necrosis factor alpha (TNF-a), and circulating markers of endothelial dysfunction/damage namely von Willebrand factor (vWF), P-selectin and the vascular adhesion molecule (VCAM-1) were measured. In comparison to healthy subjects patients had significantly higher levels of inflammatory markers: hs CRP: 2.58 mg/L (1.37-6.61), vs. 1.67 mg/L (0.97-3.24) P=0.044, IL-6: 2.37 pg/mL (1.59-4.10), vs. 2.03 pg/mL (1.45-2.59), P=0.025, IL-8: 3.53 pg/mL (2.94-5.3), vs. 2.25 pg/mL (1.77-2.90) P < or = 0.0001. However, concentrations of TNF-a did not differ significantly between the groups. Also in patients higher levels of circulating markers of endothelial dysfunction: vWF 150.0 g/L (121.0-195.0) vs. 91.5 g/L (70.5-104.0), P < or = 0.0001, P-selectin 39.5 pg/L (34.0-40.6) vs. 34.8 pg/L (32.5-38.6) P=0.009. In contrast, levels of VCAM-1 were comparable between the groups. The levels of some inflammatory markers were related to the concentration of von Willebrand factor and P-selectin - IL-6: vWF (r=0.36, P=0.08), hs CRP: P-selectin (r=0.44, P=0.018), IL-6: P-selectin (r=0.51, P=0.0002), IL-8: P-selectin (r=0.38, P=0.043). Patients with idiopathic venous thrombosis have increased levels of circulating markers of inflammation and blood markers of endothelial dysfunction. Higher levels of both groups of markers indicate that patients in the stable phase of the disease have an increased systemic inflammatory response. The interrelationship between inflammatory markers and markers of endothelial dysfunction favour the hypothesis that inflammation could be involved in the etiopathogenesis of idiopathic venous thrombosis.


Vaccination against COVID-19 and society's return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine-induced immunity.
To project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2024 in England. Deterministic, compartmental, discrete-time Susceptible-Exposed-Infectious-Recovered (SEIR) modelling. Population in England. Mass vaccination programmes. Daily and cumulative number of deaths from COVID-19. If vaccine efficacy remains high (85%), the vaccine-induced sterilising immunity lasts ≥182 days, and the reinfectivity is greatly reduced (by ≥60%), annual mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under optimistic scenarios, with annual revaccination programmes, the cumulative number of COVID-19 deaths is estimated to be from 130 000 to 150 000 by the end of 2024. However, the total number of COVID-19 deaths may be up to 431 000 by the end of 2024, under scenarios with compromised vaccine efficacy (62.5%), short duration of natural and vaccine immunity (365/182 days) and small reduction in reinfectivity (30%). Under the assumed scenarios, more frequent revaccinations are associated with smaller total numbers and lower peaks of daily deaths from COVID-19. Under optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine-induced immunity against SARS-CoV-2.


Patterns and correlates of mis-implementation in state chronic disease public health practice in the United States.
Much of the disease burden in the United States is preventable through application of existing knowledge. State-level public health practitioners are in ideal positions to affect programs and policies related to chronic disease, but the extent to which mis-implementation occurring with these programs is largely unknown. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. A 2018 comprehensive survey assessing the extent of mis-implementation and multi-level influences on mis-implementation was reported by state health departments (SHDs). Questions were developed from previous literature. Surveys were emailed to randomly selected SHD employees across the Unites States. Spearman's correlation and multinomial logistic regression were used to assess factors in mis-implementation. Half (50.7%) of respondents were chronic disease program managers or unit directors. Forty nine percent reported that programs their SHD oversees sometimes, often or always continued ineffective programs. Over 50% also reported that their SHD sometimes or often ended effective programs. The data suggest the strongest correlates and predictors of mis-implementation were at the organizational level. For example, the number of organizational layers impeded decision-making was significant for both continuing ineffective programs (OR=4.70; 95% CI=2.20, 10.04) and ending effective programs (OR=3.23; 95% CI=1.61, 7.40). The data suggest that changing certain agency practices may help in minimizing the occurrence of mis-implementation. Further research should focus on adding context to these issues and helping agencies engage in appropriate decision-making. Greater attention to mis-implementation should lead to greater use of effective interventions and more efficient expenditure of resources, ultimately to improve health outcomes.


The significance, trafficking and determination of labile iron in cytosol, mitochondria and lysosomes.
The labile iron pool (LIP) is a pool of chelatable and redox-active iron, not only essential for a wide variety of metabolic process, but also as a catalyst in the Fenton reaction, causing the release of hazardous reactive oxygen species (ROS) with potential for inducing oxidative stress and cell damage. The cellular LIP represents the entirety of every heterogenous sub-pool of iron, not only present in the cytosol, but also in mitochondria, lysosomes and the nucleus, which have all been detected and characterized by various fluorescent methods. Accumulated evidence indicates that alterations in the intracellular LIP can substantially contribute to a variety of injurious processes and initiate pathological development. Herein, we present our understanding of the role of the cellular LIP. To fully review the LIP, firstly, the significance of cellular labile iron in different subcellular compartments is presented. And then, the trafficking processes of cellular labile iron between/in cytosol, mitochondria and lysosomes are discussed in detail. Then, the recent progress in uncovering and assessing the cellular LIP by fluorescent methods have been noted. Overall, this summary may help to comprehensively envision the important physiological and pathological roles of the LIP and shed light on profiling the LIP in a real-time and nondestructive manner with fluorescent methods. Undoubtedly, with the advent and development of iron biology, a better understanding of iron, especially the LIP, may also enhance treatments for iron-related diseases.


Novel Structural Modification Based on Evans Blue Dye to Improve Pharmacokinetics of a Somastostatin-Receptor-Based Theranostic Agent.
The development of somastatin (SS) peptide analogues for the detection and treatment of neuroendocrine tumors has been successful with the recent FDA approval of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE. The structure of these peptide constructs contains the peptide binding motif that binds to the receptor with high affinity, a chelator to complex the radioactive metal, and a linker between the peptide and chelator. However, these constructs suffer from rapid blood clearance, which limits their tumor uptake. In this study, this design has been further improved by incorporating a modification to control the in vivo pharmacokinetics. Adding a truncated Evans Blue (EB) dye molecule into the construct provides a prolonged half-life in blood as a result of its low micromolar affinity to albumin. We compared 177Lu-DOTA-TATE to the modified 177Lu Evans Blue compound (177Lu-DMEB-TATE), in vitro and in vivo in mice bearing A427-7 xenografts. The tumor uptake of 177Lu-DMEB-TATE was significantly greater than the uptake of 177Lu-DOTA-TATE in the biodistribution and SPECT-imaging studies. The therapeutic effect of the 177Lu-DMEB-TATE construct was superior to the that of the 177Lu-DOTA-TATE construct at the doses evaluated.