Diet quality and the risk of cardiovascular disease: the Women's Health Initiative (WHI).
The association between diet quality and risk of incident cardiovascular disease (CVD) or heart failure (HF) in postmenopausal women is uncertain. This study aimed to determine whether a conventional index [Alternate Healthy Eating Index (AHEI)] or a novel index [Women's Health Initiative (WHI) Dietary Modification Index (DMI)] of diet quality was associated with the risk of incident CVD or HF in the WHI Observational Study (WHI-OS). The WHI-OS is an observational cohort study of 93,676 women aged 50-79 y of diverse ethnicity and backgrounds followed for an average of 10.0 y for CVD events. The individual components of the AHEI and DMI were determined from the baseline WHI food-frequency questionnaire. Incident CVD was a composite of nonfatal myocardial infarction, coronary heart disease death, stroke, coronary revascularization, and incident HF. The association between AHEI or DMI and incident CVD or incident HF was determined by using Cox models adjusted for traditional CVD and HF risk factors. Women with a DMI in the highest quintile had hazard ratios (HRs) of 0.88 (95% CI: 0.80, 0.95) and 0.91 (95% CI: 0.78, 1.06) for incident CVD and HF, respectively. Women with an AHEI in the highest quintile had HRs of 0.77 (95% CI: 0.70, 0.84) and 0.70 (95% CI: 0.59, 0.82) for incident CVD and HF, respectively. Overall, adherence to current nutrient guidelines (as indexed by the DMI) are associated with lower total CVD risk, and additional dietary factors (as indexed by the AHEI) were associated with a lower risk of CVD and HF.


Genotype-dependent response to energy-restricted diets in obese subjects: towards personalized nutrition.
Obesity is a complex disease, which in many cases appears as a polygenic condition affected by environmental factors (mainly unbalanced dietary patterns and physical inactivity). In this context, the weight loss response to dietary interventions varies widely and predictive factors of successful slimming including those concerned with the individual's genetic make-up are poorly understood. Indeed, a number of genes involved in the regulation of energy expenditure, appetite, lipid metabolism and adipogenesis have been reported to affect the risk of treatment failure in some obese subjects. Some candidate genes for the prognosis of weight loss response related to energy expenditure are those codifying for the adrenergic receptors (ADBRs) and uncoupling proteins (UCPs), while genes related to appetite potentially affected by energy restriction are leptin (LEP), leptin receptor (LEPR), melanocortin pathways genes (MC3R, POMC) and the serotonin receptor. Furthermore, adipogenesis related genes such as peroxisome proliferator-activated receptor (PPAR gamma 2) and genes related to cytokines such as interleukin-6 (IL-6) and lipid metabolism including hepatic lipase (LIPC), perilipin (PLIN) and lipoprotein lipase (LPL) have also been associated to the weight lowering outcome induced by hypocaloric diets. Therefore, this review shows preliminary evidence from human studies that support the existence of a genetic component in the fat reduction process associated to a negative energy balance.


Robust multiresolution alignment of MRI brain volumes.
An algorithm for the automatic alignment of MRI volumes of the human brain was developed, based on techniques adopted from the computer vision literature for image motion estimation. Most image registration techniques rely on the assumption that corresponding voxels in the two volumes have equal intensity, which is not true for MRI volumes acquired with different coils and/or pulse sequences. Intensity normalization and contrast equalization were used to minimize the differences between the intensities of the two volumes. However, these preprocessing steps do not correct perfectly for the image differences when using different coils and/or pulse sequences. Hence, the alignment algorithm relies on robust estimation, which automatically ignores voxels where the intensities are sufficiently different in the two volumes. A multiresolution pyramid implementation enables the algorithm to estimate large displacements. The resulting algorithm is used routinely to align MRI volumes acquired using different protocols (3D SPGR and 2D fast spin echo) and different coils (surface and head) to subvoxel accuracy (better than 1 mm).


Modeling the spread of avian influenza viruses in aquatic reservoirs: A novel hydrodynamic approach applied to the Rhône delta (southern France).
Wild aquatic birds represent a natural reservoir of avian influenza viruses (AIV) that can be spread to poultry. AIV epizootics were associated with huge economic impacts during the last decades and are still of major concern. Within aquatic bird populations AIV are transmitted either by direct contact or through the ingestion of water that has been contaminated by infected individuals. This second route involving environmental transmission is of utmost importance in AIV dynamics, yet it has received far less attention than direct bird-to-bird contamination. Our objective was to combine a hydrodynamic model with data on mallard abundance and AIV infection rate within the population, so as to characterize virus dissemination within a complex wetland network. We chose the Vaccarès hydrosystem as a wetland model since it represents a large part of the Camargue region, which is a major wintering site for a large diversity of aquatic birds including AIV hosts. We aimed to identify the environmental parameters that drive AIV dynamics within this system and the spatio-temporal pattern of dispersion and persistence of viruses. Our results show that in a complex hydrosystem we can expect a great heterogeneity in AIV risk among wetlands. Our simulations underline how a simple "homogeneous box" approach could in the case of deltaic ecosystems minimize the expected risk by diluting it in the whole system. Moreover, such undermining of the risk perception could affect the predictions relative to risk duration. We present a new approach to identify hotspots of virus concentrations within deltaic areas that could take advantage of the duck count data, AIV surveys and hydrodynamic models that may already be available in several major duck wintering areas comprised of complex hydrosystems, such as the large European deltas. Our method could be of particular interest to optimize surveillance strategies in the current context of highly pathogenic AIV diffusion within wild bird populations.


Human sympathetic ophthalmia. Immunologic analysis of the vitreous and uvea.
The inflammatory cell reaction within the vitreous and uvea of a human eye with atypical sympathetic ophthalmia was studied immunohistologically and with the fluorescence-activated cell sorter. The uveal infiltrate consisted predominantly of T cells of the helper/inducer subset, with less than 5% of the cells characterized as B cells, plasma cells, or monocytes. These results suggest that T cells perform an important role in atypical human sympathetic ophthalmia. A similar population of mononuclear cells was observed in the vitreous inflammatory infiltrate, in marked contrast to the peripheral blood, where there was a significant depression of circulating T cells. The similarity between the inflammatory cell populations within the vitreous cavity and uvea, in contrast to the peripheral blood, underlines the importance of studying the intraocular inflammatory reaction in uveitis to gain further insight into the mechanism of this disease.


Prenatal choline exposure alters hippocampal responsiveness to cholinergic stimulation in adulthood.
Manipulation of dietary choline levels during gestation results in enduring neurobehavioral changes in offspring that last into adulthood. Alterations of hippocampal function and memory are among the most striking changes. Depending upon the measures assessed, prenatal choline supplementation tends to promote excitatory synaptic efficacy in hippocampal circuits while prenatal choline deficiency diminishes it. However, the mechanisms underlying these changes remain unclear. Transverse hippocampal slices were prepared from adult offspring of dams fed choline supplemented, choline deficient, or control diets. We assessed paired-pulse inhibition, and excitatory synaptic responsiveness before and after activation of cholinergic receptors with Carbachol. Prenatally choline deficient animals yielded significantly fewer electrophysiological viable hippocampal slices than did animals from either of the other two treatment groups. Among the slices tested, there were no differences in paired pulse inhibition between the treatment groups. However, transient cholinergic activation resulted in a prolonged enhancement of the amplitude of the population EPSP (pEPSP) response in slices from prenatally choline supplemented animals. These results suggest that GABA receptor-mediated inhibition remains intact after prenatal choline manipulations, and that enhancement of the excitatory responsiveness of hippocampal circuits in slices from prenatally choline supplemented rats may be related in part to an increase in cholinergic tone within the CA1 circuit.


Pediatric nonaccidental abdominal trauma: what the radiologist should know.
Abdominal injury in nonaccidental trauma (NAT) is an increasingly recognized cause of hospitalization in abused children. Abdominal injuries in NAT are often severe and have high rates of surgical intervention. Certain imaging findings in the pediatric abdomen, notably bowel perforation and pancreatic injury, should alert the radiologist to possible abuse and incite close interrogation concerning the reported mechanism of injury. Close inspection of the imaging study is warranted to detect additional injury sites because these injuries rarely occur in isolation. When abdominal injury is suspected in known or speculated NAT, computed tomography (CT) of the abdomen and pelvis with intravenous contrast material is recommended for diagnostic and forensic evaluation. Although the rate of bowel injury is disproportionately high in NAT, solid organs, including the liver, pancreas, and spleen, are most often injured. Adrenal and renal trauma is less frequent in NAT and is generally seen with multiple other injuries. Hypoperfusion complex is a constellation of abdominal CT findings that indicates current or impending decompensated shock and is most often due to severe neurologic impairment in NAT. Although abdominal injuries in NAT are relatively uncommon, knowledge of injury patterns and their imaging appearances is important for patient care and protection.


Clinical treatment considerations in the intensity-modulated radiotherapy era for patients with N0-category nasopharyngeal carcinoma and enlarged neck lymph nodes.
Nasopharyngeal carcinoma (NPC) shows a high proportion of lymph node metastasis, and treatment guidelines have been developed for positive nodes. However, no irradiation guidelines have been proposed for patients with enlarged neck lymph nodes (ENLNs) that do not meet the radiological criteria of 10 mm in diameter for positive lymph nodes. This study aimed to determine the prognostic value and radiation dose for ENLNs in N0-category NPC patients treated with intensity-modulated radiotherapy (IMRT). We reviewed the medical data of 251 patients with non-metastatic, N0-category NPC treated with IMRT. Receiver operating characteristic curves were used to calculate the cut-off value of the ENLN diameter for the prediction of disease failure. The biological equivalent dose (BED) for ENLNs was calculated. Patient survival was compared between the small and large ENLN groups. Independent prognostic factors were identified using the Cox proportional hazards model. The estimated 4-year regional relapse-free survival rate was higher in patients with ENLNs ≥5.5 mm than in those with ENLNs <5.5 mm (100% vs. 98.8%, P = 0.049), whereas disease-free, overall, and distant metastasis-free survival rates were similar between the two groups. After adjusting for various factors, ENLN diameter was not identified as an independent prognostic factor (P > 0.05 for all survival rates). In the subgroup analysis, patients receiving BED ≥72 Gy had a similar prognosis as patients receiving BED <72 Gy in both the small and large ENLN groups. The multivariate analysis also confirmed that BED ≥72 Gy was not associated with significantly improved prognosis in patients with N0-category NPC. A BED of 72 Gy to ENLNs is considerably sufficient to provide a clinical benefit to patients with N0-category NPC. Prospective studies are warranted to validate the findings in the present study.


Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice.
A single administration of complete Freund's adjuvant (CFA), type 1 carrageenan (Car), or silica 7, 2, and 2 days, respectively, before infection with a low dose (1 x 10(2) plaque-forming units/mouse) of encephalomyocarditis D (EMC-D) virus resulted in a significant increase in the incidence of diabetes in SJL/J mice (100%) compared with untreated EMC-D virus-infected mice (40%). Peritoneal macrophages were isolated from uninfected SJL/J mice, which had been treated once with silica, and transferred into SJL/J mice 2 days before low-dose EMC-D infection. Approximately 90% of the mice became diabetic, whereas 30% of mice that received virus alone became diabetic. The depletion of macrophages by treatment with the combined anti-Mac-1 and anti-Mac-2 monoclonal antibodies after a single administration of CFA, Car, or silica resulted in almost complete prevention of beta-cell destruction in EMC-D virus-infected mice. Furthermore, none of the mice in which macrophages were depleted by long-term treatment with silica and 10% of the mice treated with Car before virus infection became diabetic. On the basis of these observations, we conclude that macrophages are directly involved in the destruction of beta-cells, leading to the development of clinical diabetes in EMC-D virus-infected mice.


Comparison of the effects of neurokinin-3 receptor blockade on two forms of slow synaptic transmission in myenteric AH neurons.
AH neurons are intrinsic sensory neurons of the intestine that exhibit two types of slow synaptic event: slow excitatory postsynaptic potentials which increase their excitability for about 2-4 min, and sustained slow postsynaptic excitation which can persist for several hours, and may be involved in long-term changes in the sensitivity of the intestine to sensory stimuli. The effects of the neurokinin-3 tachykinin receptor antagonist, SR142801, on these two types of synaptic event in AH neurons of the myenteric ganglia of guinea-pig small intestine were compared. Slow excitatory postsynaptic potentials were evoked by stimulation of synaptic inputs at 10-20 Hz for 1s, and sustained slow postsynaptic excitation was evoked by stimulation of inputs at 1Hz for 4 min. SR142801 (1microM) reduced the amplitude of the slow excitatory postsynaptic potential to 26% of control, and also reduced the increase in input resistance and the extent of anode break excitation associated with the slow excitatory postsynaptic potential. In contrast, SR142801 did not reduce the increase in excitability, the increase in input resistance or the depolarisation that occur during the sustained slow postsynaptic excitation. SR142801 did not change the resting membrane potential or the resting input resistance. We conclude that tachykinins, acting through neurokinin-3 receptors, are involved in the generation of the slow excitatory postsynaptic potential, but not in the sustained slow postsynaptic excitation, and that the release of transmitters from synaptic inputs to AH neurons is frequency coded.


A Very Rare Localization of Rhinolith: Fossa of Rosenmuller.
Sixty-five-year old male patient applied to our clinic with nonspecific complaints such as tinnitus, otalgia, headache, halitosis, and persistent globus pharyngeus which had been continued for 5 years. His complaints persisted despite different extensive treatments. In nasoendoscopy, a yellow-colored mass with purulent discharge around was observed in eustachian tube opening in left fossa of Rosenmüller. Computed tomography scan showed a mass of 6 × 6 mm size in left fossa of Rosenmüller. After excision of the mass under local anesthesia, significant reductions were observed in patient's symptoms. Histopathology of the mass was reported as rhinolith. Although fossa of Rosenmüller is a quite rare localization for rhinoliths, it needs to be considered in differential diagnosis of patients with nonspecific symptoms such as halitosis, globus pharyngeus, and otalgia. This report represents a patient with rhinolith localized in fossa of Rosenmüller as the 2nd report in the literature.


How do Amateur Endurance Runners Alter Spatiotemporal Parameters and Step Variability as Running Velocity Increases? a Sex Comparison.
This study aimed to analyse the effects of running velocity on spatiotemporal parameters and step variability in amateur endurance runners, according to sex. A group of 51 males and 46 females performed an incremental running test on a treadmill (10-16 km/h). Spatiotemporal parameters (contact and flight time, step length, step frequency and step angle [CT, FT, SL, SF, SA]) and step variability, in terms of within-participant standard deviation (SD), were recorded through the OptoGait System. The ANOVA showed significant differences in the magnitude of the spatiotemporal parameters as running velocity increased (p < 0.001). It also revealed significant differences in step variability (p < 0.005) over the entire running protocol. Between-sex differences in CT, SL, SL-normalized and SF (p < 0.05, ES = 0.4-0.8) were found. Differences were also found in step variability at high velocities (15-16 km/h), with males showing a greater SD than females. In conclusion, increasing running velocity makes CT shorter, FT and SL longer, and SF and SA greater in amateur endurance runners, changing step variability, regardless of sex. Additionally, some between-sex differences were found in spatiotemporal parameters and step variability.


Concerted action of two avirulent spore effectors activates Reaction to Puccinia graminis 1 (Rpg1)-mediated cereal stem rust resistance.
The barley stem rust resistance gene Reaction to Puccinia graminis 1 (Rpg1), encoding a receptor-like kinase, confers durable resistance to the stem rust pathogen Puccinia graminis f. sp. tritici. The fungal urediniospores form adhesion structures with the leaf epidermal cells within 1 h of inoculation, followed by hyphae and haustorium formation. The RPG1 protein is constitutively expressed and not phosphorylated. On inoculation with avirulent urediniospores, it is phosphorylated in vivo within 5 min and subsequently degraded. Application of arginine-glycine-aspartic acid peptide loops prevented the formation of adhesion structures for spore attachment, the phosphorylation of RPG1, and germination of the viable spores. Arginine-glycine-aspartic acid affinity chromatography of proteins from the ungerminated avirulent rust spores led to the purification and identification of a protein with fibronectin type III and breast cancer type 1 susceptibility protein domains and a vacuolar protein sorting-associated protein 9 with a coupling of ubiquitin to endoplasmic reticulum degradation domain. Both proteins are required to induce in vivo phosphorylation and degradation of RPG1. Combined application of both proteins caused hypersensitive reaction on the stem rust-resistant cultivar Morex but not on the susceptible cultivar Steptoe. Expression studies indicated that mRNA of both genes are present in ungerminated urediniospores and are constitutively transcribed in sporelings, infected leaves, and haustoria in the investigated avirulent races. Evidence is presented that RPG1, in yeast, interacts with the two protein effectors from the urediniospores that activate cooperatively the stem rust resistance protein RPG1 long before haustoria formation.


Psychotherapy for depression in children and adolescents: study protocol for a systematic review and network meta-analysis.
Depression is common among children and adolescents and is associated with significantly negative effects. A number of structured psychosocial treatments are administered for depression in children and adolescents; however, evidence of their effectiveness is not clear. We describe the protocol of a systematic review and network meta-analysis to evaluate the efficacy, quality of life, tolerability and acceptability of the use of psychological intervention for this young population. We will search PubMed, EMBASE, CENTRAL (the Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS, Dissertation Abstracts, European Association for Grey Literature Exploitation (EAGLE) and the National Technical Information Service (NTIS) from inception to July 2014. There will be no restrictions on language, publication year or publication type. Only randomised clinical trials (RCTs) with psychosocial treatments for depression in children and adolescents will be considered. The primary outcome of efficacy will be the mean overall change of the total score in continuous depression severity scales from baseline to end point. Data will be independently extracted by two reviewers. Traditional pairwise meta-analyses will be performed for studies that directly compared different treatment arms. Then we will perform a Bayesian network meta-analyses to compare the relative efficacy, quality of life, tolerability and acceptability of different psychological intervention. Subgroup analyses will be performed by the age of participants and the duration of psychotherapy, and sensitivity analyses will be conducted to assess the robustness of the findings. No ethical issues are foreseen. The results will be published in a peer-reviewed journal and disseminated electronically and in print. The meta-analysis may be updated to inform and guide management of depression in children and adolescents. PROSPERO CRD42014010014.


Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase.
Tetrahydrobiopterin (BH4) serves as a critical co-factor for the endothelial nitric-oxide synthase (eNOS). A deficiency of BH4 results in eNOS uncoupling, which is associated with increased superoxide and decreased NO* production. BH4 has been suggested to be a target for oxidation by peroxynitrite (ONOO-), and ascorbate has been shown to preserve BH4 levels and enhance endothelial NO* production; however, the mechanisms underlying these processes remain poorly defined. To gain further insight into these interactions, the reaction of ONOO- with BH4 was studied using electron spin resonance and the spin probe 1-hydroxy-3-carboxy-2,2,5-tetramethyl-pyrrolidine. ONOO- reacted with BH4 6-10 times faster than with ascorbate or thiols. The immediate product of the reaction between ONOO- and BH4 was the trihydrobiopterin radical (BH3.), which was reduced back to BH4 by ascorbate, whereas thiols were not efficient in recycling of BH4. Uncoupling of eNOS caused by peroxynitrite was investigated in cultured bovine aortic endothelial cells (BAECs) by measuring superoxide and NO* using spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine and the NO*-spin trap iron-diethyldithiocarbamate. Bolus ONOO-, the ONOO- donor 3-morpholinosydnonimine, and an inhibitor of BH4 synthesis (2,4-diamino-6-hydroxypyrimidine) uncoupled eNOS, increasing superoxide and decreasing NO* production. Exogenous BH4 supplementation restored endothelial NO* production. Treatment of BAECs with both BH4 and ascorbate prior to ONOO- prevented uncoupling of eNOS by ONOO-. This study demonstrates that endothelial BH4 is a crucial target for oxidation by ONOO- and that the BH4 reaction rate constant exceeds those of thiols or ascorbate. We confirmed that ONOO- uncouples eNOS by oxidation of tetrahydrobiopterin and that ascorbate does not fully protect BH4 from oxidation but recycles BH3. radical back to BH4.


Insights into Vapor-Mediated Interactions in a Nanocolloidal Droplet System: Evaporation Dynamics and Affects on Self-Assembly Topologies on Macro- to Microscales.
Particle-laden droplet-based systems ranging from micro- to nanoscale have become increasingly popular in applications such as inkjet printing, pharmaceutics, nanoelectronics, and surface patterning. All such applications involve multidroplet arrays in which vapor-mediated interactions can significantly affect the evaporation dynamics and morphological topology of precipitates. A fundamental study was conducted on nanocolloidal paired droplets (droplets kept adjacent to each other as in an array) to understand the physics related to the evaporation dynamics, internal flow pattern, particle transport, and nanoparticle self-assembly, primarily using optical diagnostic techniques [such as micro-particle image velocimetry (μPIV)]. Paired droplets exhibit contact angle asymmetry, inhomogeneous contact line slip, and unique single-toroid microscale flow, which are unobserved in single droplets. Furthermore, nanoparticles self-assemble (at the nanoscale) to form a unique variable-thickness (microscale) tilted dome-shaped structure that eventually ruptures at an angle because of evaporation at a nanopore scale to form cavities (miniscale). The geometry and morphology of the dome can be further fine-tuned at a macro- to microscale by varying the initial particle concentration and substrate properties. This concept has been extended to a linear array of droplets to showcase how to custom design two-dimensional drop arrangements to create controlled surface patterns at multiple length scales.


Maternal health and social outcomes after having a child taken into care: population-based longitudinal cohort study using linkable administrative data.
We investigated whether mothers experience changes to their health and social situation after having a child taken into care by child protection services, then compared these outcomes with those found in mothers whose children were not taken into care. The cohort includes mothers whose first child was born in Manitoba between 1 April 1998 and 31 March 2011. Mothers whose children were taken into care after age 2 (n=1591) were compared with a matched group of women whose children were not taken into care (n=1591). The rates of mental illness diagnoses, treatment use and social factors were significantly higher for mother whose children were taken into care, both in the 2 years before and in the 2 years after the index date. These adjusted relative rates (ARRs) increased significantly for anxiety (before ARR=2.71, after ARR=3.55), substance use disorder (3.77-5.95), physician visits for mental illness (2.83-3.66), number of prescriptions (psychotropic: 4.35-5.86; overall: 2.34-2.94), number of different prescriptions (psychotropic: 2.70-3.27; overall: 1.62-1.70), residential mobility (1.40-1.63) and welfare use (2.07-2.30). The health and social situation of mothers involved with child protection services deteriorates after their child is taken into care. Mothers would benefit from supports during this time period to ensure that the outcomes they experience after the loss of their child do not become another barrier to reunification.


[Treatment of heart wounds].
Care results in 48 patients (male--38, female--10) with heart wounds (HW) were analyzed. 40 (83.2%) patients had stab-incised wounds, 7 (14.7%)--stab wounds, 1 (2.1%)--gunshot wounds. 23 (47.8%) patients were hospitalized in consciousness, 17 (35.3%)--in unconsciousness, 8 (16.9%)--in twilight state. The lethality among the latter two groups of the patients was 64%, in the former group--13%. 19 patients from 48 died: in preoperative period--3, during operation--10, in early postoperative period (more than 10 days)--2 patients. The suspected of HW patients must be transported in the nearest surgical hospital. In unstable hemodynamics it is necessary to carry out adequate infusion therapy, in obvious signs of heart tamponade the pericardium puncture must be performed. In agonizing patients, and in case of general anesthesia delay, it is necessary to begin thoracotomy before general anesthesia.


Domestic pigs are susceptible to infection with influenza B viruses.
Influenza B virus (IBV) causes seasonal epidemics in humans. Although IBV has been isolated from seals, humans are considered the primary host and reservoir of this important pathogen. It is unclear whether other animal species can support the replication of IBV and serve as a reservoir. Swine are naturally infected with both influenza A and C viruses. To determine the susceptibility of pigs to IBV infection, we conducted a serological survey for U.S. Midwest domestic swine herds from 2010 to 2012. Results of this study showed that antibodies to IBVs were detected in 38.5% (20/52) of sampled farms, and 7.3% (41/560) of tested swine serum samples were positive for IBV antibodies. Furthermore, swine herds infected with porcine reproductive and respiratory syndrome virus (PRRSV) showed a higher prevalence of IBV antibodies in our 2014 survey. In addition, IBV was detected in 3 nasal swabs collected from PRRSV-seropositive pigs by real-time RT-PCR and sequencing. Finally, an experimental infection in pigs, via intranasal and intratracheal routes, was performed using one representative virus from each of the two genetically and antigenically distinct lineages of IBVs: B/Brisbane/60/2008 (Victoria lineage) and B/Yamagata/16/1988 (Yamagata lineage). Pigs developed influenza-like symptoms and lung lesions, and they seroconverted after virus inoculation. Pigs infected with B/Brisbane/60/2008 virus successfully transmitted the virus to sentinel animals. Taken together, our data demonstrate that pigs are susceptible to IBV infection; therefore, they warrant further surveillance and investigation of swine as a potential host for human IBV. IBV is an important human pathogen, but its ability to infect other species, for example, pigs, is not well understood. We showed serological evidence that antibodies to two genetically and antigenically distinct lineages of IBVs were present among domestic pigs, especially in swine herds previously infected with PRRSV, an immunosuppressive virus. IBV was detected in 3 nasal swabs from PRRSV-seropositive pigs by real-time reverse transcription-PCR and sequencing. Moreover, both lineages of IBV were able to infect pigs under experimental conditions, with transmissibility of influenza B/Victoria lineage virus among pigs being observed. Our results demonstrate that pigs are susceptible to IBV infections, indicating that IBV is a swine pathogen, and swine may serve as a natural reservoir of IBVs. In addition, pigs may serve as a model to study the mechanisms of transmission and pathogenesis of IBVs.


Role of high-dose melphalan and autologous peripheral blood stem cell transplantation in AL amyloidosis.
AL amyloidosis is the most common form of systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. The disease is often difficult to recognize because of its broad range of manifestations and, what are often, vague symptoms. Recent diagnostic and prognostic advances include the serum free light chain assay, cardiac magnetic resonance imaging, and serologic cardiac biomarkers. Treatment strategies that have evolved during the past decade are prolonging survival and preserving organ function in patients with this disease. This review outlines the role of high dose melphalan and stem cell transplantation in the treatment of AL amyloidosis.


Numerical investigation of the relative effect of disc bulging and ligamentum flavum hypertrophy on the mechanism of central cord syndrome.
The pathogenesis of the central cord syndrome is still unclear. While there is a consensus on hyperextension as the main traumatic mechanism leading to this condition, there is yet to be consensus in studies regarding the pathological features of the spine (intervertebral disc bulging or ligamentum flavum hypertrophy) that could contribute to clinical manifestations. A comprehensive finite element model of the cervical spine segment and spinal cord was used to simulate high-speed hyperextension. Four stenotic cases were modelled to study the effect of ligamentum flavum hypertrophy and intervertebral disc bulging on the von Mises stress and strain. During hyperextension, the downward displacement of the ligamentum flavum and a reduction of the spinal canal diameter (up to 17%) led to a dynamic compression of the cord. Ligamentum flavum hypertrophy was associated with stress and strain (peak of 0.011 Mpa and 0.24, respectively) in the lateral corticospinal tracts, which is consistent with the histologic pattern of the central cord syndrome. Linear intervertebral disc bulging alone led to a higher stress in the anterior and posterior funiculi (peak 0.029 Mpa). Combined with hypertrophic ligamentum flavum, it further increased the stress and strain in the corticospinal tracts and in the posterior horn (peak of 0.023 Mpa and 0.35, respectively). The stenotic typology and geometry greatly influence stress and strain distribution resulting from hyperextension. Ligamentum flavum hypertrophy is a main feature leading to central cord syndrome.


Cardiac beta-adrenoceptor sensitivity and Parkinson's disease.
Certain clinical manifestations of Parkinson's disease (PD) (speech or/and balance disturbances) are not linked to brain dopamine deficiency. The purpose of the present study was to search for a possible relationship between those so-called "non-dopamine-dependent" extrapyramidal manifestations and the sensitivity of cardiac beta-adrenoceptors. Fourteen patients aged 51 to 69 were included in the study after having given their informed consent. Any factor or pathology susceptible to modify receptor sensitivity entailed exclusion. In the absence of a reference model for measuring the reactivity of central beta-adrenoceptors, a computation of the isoprenalin dose necessary to increase the resting heart rate by 20 bpm was used as an index for beta-adrenergic system reactivity. In addition to that test, other parameters were recorded: disease duration, motor status scale (Columbia), some cognitive functions (MMS and image differed recall). The cardiac beta-receptor decrease in reactivity to isoproterenol is correlated to PD duration (r = 0.8, P less than 0.001). Conversely, the sensitivity of these receptors appeared to be unrelated to the extrapyramidal severity of the disease, hence to the degree of the so-called "non dopamine-dependent" disturbances. Furthermore, such results raise the meaning of the impairment of peripheral aminergic receptors in the cognitive disturbances linked to ageing and/or PD.


Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains.
The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development.


Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation.
Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally. Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems. Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not. Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.


Pharmacokinetics of theanine enantiomers in rats.
Theanine, first discovered in tea, is a chiral nonproteinic amino acid that has been reported to have cardiovascular, neurological, and oncological effects. It is being considered as a therapeutic/medicinal agent and additive in consumer products. The present study evaluated the pharmacokinetics of D-theanine, L-theanine, and D,L-theanine in plasma and urine using LC-ESI/MS in rats after oral (p.o.) and intraperitoneal (i.p.) administration. Oral administration data indicated that gut absorption of d-theanine was far less than that of L-theanine. However, after i.p. administration, plasma theanine concentrations of L- and D-theanine were similar. This indicated that D- and L-theanine may exhibit a competitive effect with respect to intestinal absorption. Regardless of the route of administration, p.o. or i.p., the presence of the other enantiomer always decreased theanine plasma concentrations, indicating D,L-theanine competition with respect to urinary reabsorption. Data on urinary concentrations of D-theanine suggested that the D-isomer may be eliminated with minimal metabolism. L-Theanine appeared to be preferentially reabsorbed and metabolized by the kidney while D-theanine was preferentially excreted. Clearly, the bioequivalencies of D,L-theanine and its enantiomers were found to be quite different from one another. Consequently, the efficacy of commercial theanine products containing D-theanine, L-theanine, or D,L-theanine may be quite different.


Results of the intravenous administration of tropisetron in fibromyalgia patients.
The observed effects on the symptoms of fibromyalgia of daily oral administration of 5 mg of the 5-HT3 receptor antagonist, tropisetron, for 10 days, could be maintained or exceeded with intravenous administration of only 2 mg of the formulation. Following a single i.v. injection of 2 mg tropisetron, a more rapid and profound reduction in pain was achieved than with 5 mg oral tropisetron per day. In individual cases, patients who had previously experienced no reduction in pain from 10 days of 5 mg oral tropisetron daily responded to i.v. therapy. A more favourable and persistent effect on pain, combined with a simultaneous significant improvement in various vegetative and functional symptoms was achieved with five days treatment with 2 mg tropisetron i.v. per day. The results outlined and the possibility for rapid improvements with drug treatment of fibromyalgia should be confirmed in randomised, placebo controlled trials.


Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt.
Vascular endothelial growth factor (VEGF) binds both VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2). Activation of VEGFR-2 is thought to play a major role in the regulation of endothelial function by VEGF. Recently, specific ligands for VEGFR-1 have been reported to have beneficial effects when used to treat ischemic diseases. However, the role of VEGFR-1 in angiogenesis is not fully understood. In this study, we showed that VEGFR-1 performs "fine tuning" of VEGF signaling to induce neovascularization. We examined the effects of retroviral vectors expressing a small interference RNA that targeted either the VEGFR-1 gene or the VEGFR-2 gene. Deletion of either VEGFR-1 or VEGFR-2 reduced the ability of endothelial cells to form capillaries. Deletion of VEGFR-1 markedly reduced endothelial cell proliferation and induced premature senescence of endothelial cells. In contrast, deletion of VEGFR-2 significantly impaired endothelial cell survival. When VEGFR-1 expression was blocked, VEGF constitutively activated Akt signals and thus induced endothelial cell senescence via a p53-dependent pathway. VEGFR-1(+/-) mice exhibited an increase of endothelial Akt activity and showed an impaired neovascularization in response to ischemia, and this impairment was ameliorated in VEGFR-1(+/-) Akt1(+/-) mice. These results suggest that VEGFR-1 plays a critical role in the maintenance of endothelial integrity by modulating the VEGF/Akt signaling pathway.


Loss of resting interhemispheric functional connectivity after complete section of the corpus callosum.
Slow (<0.1 Hz), spontaneous fluctuations in the functional magnetic resonance imaging blood oxygen level-dependent (BOLD) signal have been shown to exhibit phase coherence within functionally related areas of the brain. Surprisingly, this phenomenon appears to transcend levels of consciousness. The genesis of coherent BOLD fluctuations remains to be fully explained. We present a resting state functional connectivity study of a 6-year-old child with a radiologically normal brain imaged both before and after complete section of the corpus callosum for the treatment of intractable epilepsy. Postoperatively, there was a striking loss of interhemispheric BOLD correlations with preserved intrahemispheric correlations. These unique data provide important insights into the relationship between connectional anatomy and functional organization of the human brain. Such observations have the potential to increase our understanding of large-scale brain systems in health and disease as well as improve the treatment of neurologic disorders.


The incidence of mismatch repair gene defects in colorectal liver metastases.
Knowledge of the molecular biology of primary colorectal cancer (CRC) has improved in recent years, and one reason for this is the identification of microsatellite instability (MSI), which occurs in up to 15% of sporadic CRC. However, less is known regarding the processes involved in colorectal liver metastases (CRLM). Increasing numbers of patients with CRLM are suitable for curative resection, so the identification of molecular markers may improve patient selection. The aim of the present study was to characterise the incidence of MSI in resected CRLM. Fifty‑one sequentially resected CRLM specimens were selected. Clinicopathologic data was collated and immunohistochemistry for MLH1 and MSH2 was performed on paraffin sections of the CRLM specimens. The association between abnormal staining and the clinicopathological data was examined. The median age of the subjects in the current study was 65 years, the average number of CRLM was 2 and the median overall survival time was 42.1 months post liver resection. None of the 50 resected specimens demonstrated abnormal staining for MLH1 or MSH2. Compared with the previously reported incidence of MSI in primary CRC, the low incidence of MSI in the current cohort of CRLM precludes its use as a marker for use in making clinical decisions regarding this condition.


Mitral valve annular bacterial vegetative mass masquerading as a left atrial myxoma.
A 49-year-old male with chronic kidney disease and history of renal transplantation in 2006 on chronic immunosuppressant therapy presented with a 1-week history of chills and generalized myalgia. He had a temperature of 101 degrees F. One set of blood cultures grew methicillin-sensitive Staphylococcus aureus. Transesophageal echo (TEE) revealed a mobile mass that was 2 cm in length attached by a thin stalk to the base of the anterior leaflet of the mitral valve. The surgical diagnosis was a left atrial myxoma. The echocardiographic as well as the surgical findings were consistent with an atrial myxoma. However, the histopathology of the specimen showed no evidence of myxoma as the characteristic stellate mesenchymal cells were absent. Instead the milieu of inflammatory cells, fibrin and multimicrobial colonization of both Gram-positive and Gram-negative cocci suggested a super infected vegetative mass. It is interesting that the mitral valve was intact as de novo vegetation being formed on a structurally normal native valve is rare. In some instances, the echocardiographic distinction between atrial masses such as vegetation, thrombus or an atrial myxoma may be ambiguous. Not only does surgical removal allow histological determination of the diagnosis that is critical for treatment, but in cases where an infected mass is mobile and greater than 15 mm, as in this case, there is high potential for embolization. Surgical removal significantly decreases the risk of an embolic event.


Radiographic and Clinical Outcomes Following Pedicle Subtraction Osteotomy : Minimum 2-Year Follow-Up Data.
The purpose of this study was to report the results of pedicle subtraction osteotomy (PSO) for fixed sagittal imbalance with a minimum 2-year follow-up. Besides, authors evaluated the effect of adjunctive multi-level posterior column osteotomy (PCO) on achievement of additional lumbar lordosis (LL) during PSO. A total of 31 consecutive patients undergoing PSO for fixed sagittal imbalance were enrolled and analyzed. Correction angle of osteotomized vertebra (PSO angle) and other radiographic parameters including pelvic incidence (PI), thoracic kyphosis, LL, and sagittal vertical axis (SVA) were evaluated. Clinical outcomes and surgical complications were also assessed. The mean age was 66.0±9.3 years with a mean follow-up period of 33.2±10.5 months. The mean number of fused segments was 9.6±3.5. The mean operative time and surgical bleeding were 475.9±160.5 minutes and 1406.1±932.1 mL, respectively. The preoperative SRS-22 score was 2.3±0.7 and improved to 3.2±0.8 at the final follow-up. The mean PI was 54.5±9.5°. LL was changed from 7.0±28.9° to -50.2±13.2°. The PSO angle was 33.7±13.5° (15.6±20.1° preoperatively, -16.1±19.4° postoperatively). The difference of correction angle of LL (57.3°) was greater about 23.6° than which of PSO angle (33.7°). SVA was improved from 189.5±93.0 mm, preoperatively to 12.4±40.8 mm, postoperatively. There occurred six, eight, and 14 cases of complications at intraoperative, early (<2 weeks) postoperative, and late (≥2 weeks) postoperative period, respectively. Additional operations were needed in nine patients due to the complications. PSO could provide satisfactory results for patients with fixed sagittal imbalance regarding clinical and radiographic outcomes. Additional correction of LL could be achieved with conduction of adjunctive multi-level PCOs during PSO.


The enigma of the gene coding for ribosomal protein S12 in the chloroplasts of Nicotiana.
A 2.9 kbp region from within the inverted repeat of Nicotiana chloroplast DNA hybridized with a chloroplast DNA fragment from Euglena containing the complete rps12 gene coding for ribosomal protein S12. Nucleotide sequencing within this region revealed the existance of two rps12 coding stretches interrupted by 540 bp having class II intron structure. Joining and decoding the exon regions produced a sequence of 85 amino acids colinear and 81% homologous to the S12 protein of Euglena chloroplasts and E. coli, starting from amino acid residue 38 to the stop codon. Immediately upstream of codon 38, conserved intron sequences were located. However, the 5' 37 codon of Nicotiana chloroplast rps12 could not be identified by electron microscopy of RNA-DNA hybrids within a DNA region extending 4000 bp upstream of codon 38, nor by computer search of a completely sequenced region extending for more than 9000 bp upstream of this codon. In E. coli, alteration in rps12 codons 42 or 87 causes streptomycin resistance. However, the nucleotide sequence of the identified rps12 exons in two Nicotiana chloroplast mutants resistant to streptomycin were found to be identical to that of wild type.


A clinical study of edentulous patients rehabilitated according to the "all on four" immediate function protocol.
The aim of this study was to compare definitive acrylic resin prostheses with or without a cast metal framework that were immediately loaded and supported by axial and tilted implants in completely edentulous patients after 3 years of function. Patients who were completely or partially edentulous in one or both arches with severe atrophy of the posterior regions were selected for this study. All patients immediately received prosthetic rehabilitations, each supported by four implants (two axial and two tilted). The patients were randomized to receive a definitive prosthesis with a cast metal framework or one made of acrylic resin only. Follow-up visits were performed up to 36 months after implant insertion and included radiographic assessments of bone levels around the implants. Thirty-six patients participated, and 44 complete-arch immediately loaded prostheses (24 maxillary and 20 mandibular), each supported by four implants (in total 176 implants), were placed. In all, 21 screw-retained full-arch acrylic resin prostheses and 23 cast-metal-framework prostheses were delivered to the patients. The 3-year overall implant survival rate was 100% for axially positioned implants and 96.59% for tilted implants. Implant survival rates were 98.96% in the maxilla and 97.5% in the mandible. None of the 44 fixed prostheses were lost during the observation period, representing a prosthetic survival rate of 100%. No statistically significant differences were seen in crestal bone loss between tilted and axial implants at 12, 24, and 36 months in either arch. The same clinical outcome was seen for patients treated with the so-called All on Four protocol, regardless of whether the acrylic resin restorations were reinforced with metal.


Implications of Prenatal Exposure to the Spring 2011 Alabama and Missouri Tornadoes on Birth Outcomes.
Despite emerging evidence of the detrimental effects of natural disasters on maternal and child health, little is known about exposure to tornadoes during the prenatal period and its impact on birth outcomes. We examined the relationship between prenatal exposure to the spring 2011 tornado outbreak in Alabama and Joplin (Missouri) and adverse birth outcomes. We conducted a retrospective, cross-sectional cohort study using the 2010-2012 linked infant births and deaths data set from the National Center for Health Statistics for tornado-affected counties in Alabama (n=126,453) and Missouri (Joplin, n=6,897). Chi-square and logistic regression analyses were performed to estimate associations between prenatal exposure to tornadoes and birth outcomes. Prenatal exposure to the tornado incidents did not influence birth weight outcomes. Women exposed to Alabama tornadoes were less likely to have a preterm birth compared to unexposed mothers (OR: 0.93, 95% CI: 0.91, 0.96). Preterm births among Joplin-tornado exposed mothers were slightly higher (13%) compared with unexposed mothers (11.2%). Exposed mothers from Joplin were also more likely to have a cesarean section compared to their counterparts (OR: 1.14, 95% CI: 1.02, 1.26). We found no association between tornado exposure and adverse birth weight and infant mortality rates. Our findings suggest that prenatal exposure can amplify the odds for a cesarean section. (Disaster Med Public Health Preparedness. 2019;13:279-286).


'A kiss that took my legs away': a rare presentation of Epstein-Barr virus in the older population.
We present the case of a 70-year-old woman presenting with nausea, diarrhoea and a generalised rash. Initial blood tests revealed obstructive deranged liver function tests and low haemoglobin. A haemolysis screen revealed raised reticulocytes, low haptoglobin and a positive direct antiglobulin test. 6 days into her admission, she developed lower limb weakness and loss of sensation. MRI spine showed no significant findings. Cerebrospinal fluid showed raised white blood cell count and raised protein. Nerve conduction studies were normal. The clinical picture was in keeping with transverse myelitis. Autoimmune and viral screens were negative except for a single result which provided the unifying diagnosis: Epstein-Barr virus (EBV). She responded to high dose intravenous corticosteroids and her rehabilitation is ongoing. EBV should be considered even in the older population.


Boards of Directors: Assessing Their Functioning and Validation of a Multi-Dimensional Measure.
Boards of Directors that function effectively have been shown to be associated with successful organizational performance. Although a number of measures of Board functioning have been proposed, very little research has been conducted to establish the validity and reliability of dimensions of Board performance. The aim of the current study was to validate the measurement properties of a widely-used model and measure of Board performance. Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were conducted on online survey data collected from 1,546 board members from a range of Australian organizations. The analyses yielded 11 reliable factors: (1) effective internal communication and teamworking (2) effective leadership by the Chair (3) effective committee leadership and management (4) effective meeting management and record keeping, (5) effective information management (6) effective self-assessment of board functioning (7) effective internal performance management of board members (8) clarity of board member roles and responsibilities, (9) risk and compliance management (10) oversight of strategic direction, and (11) remuneration management. These dimensions to a large extent correspond to previously suggested, but not widely tested, categories of effective Board performance. Despite self-reported data and a cross-sectional design, tests of common method variance did not suggest substantive method effects. The research makes significant contributions to the corporate governance literature through empirical validation of a measure shown to reliably assess 11 discrete dimensions of Board functioning and performance. Practical and theoretical implications, study limitations and future research considerations are presented.


Reliability, validity and distribution of the Spanish female sexual function index in women with relapsing multiple sclerosis.
The Female Sexual Function Index (FSFI) is a widely recognized tool for assessing sexual dysfunction (SD). However, its validation for Spanish women suffering from multiple sclerosis (MS) has not yet been conducted. The study aimed to examine the psychometric properties of the 19-item Spanish version of the FSFI (svFSFI) in women with relapsing MS. A total of 137 women with relapsing MS from three Spanish centers participated in the study and completed the svFSFI. The psychometric properties of the questionnaire were evaluated. The prevalence of SD in the study cohort was determined, and its association with clinical and sociodemographic variables was analyzed using bi- and multivariate regression analyses. The svFSFI demonstrated excellent test-retest reliability and substantial-to-excellent internal consistency in the context of relapsing MS. There was significant convergent validity in the intercorrelations of domains. Discriminant validity showed differences in SD between women with high and low neurological disability, as measured by the Expanded Disability Status Scale (EDSS) scores. An exploratory factor analysis indicated a five-factor structure for the svFSFI. The prevalence of SD in the MS cohort was found to be 42.6%, with the 'desire' and 'arousal' domains being the most affected. Factors such as EDSS score, fatigue, depression, and having a stable partner were found to influence the total svFSFI score. The study validates the svFSFI as a reliable and valid instrument for evaluating sexual dysfunction in Spanish women with MS.


Tacrolimus rescue in liver transplant patients with refractory rejection or intolerance or malabsorption of cyclosporine. The US Multicenter FK506 Liver Study Group.
Tacrolimus is an effective immunosuppressant in the rescue of liver allograft patients in whom conventional immunosuppression failed. Efficacy and safety were examined in a multicenter trial of liver transplant recipients converted to tacrolimus because of rejection despite cyclosporine (CyA) therapy or intolerance to CyA. Six hundred seventy-seven patients were enrolled onto the study; 475 patients for rejection, 197 patients for intolerance, and 5 patients treated compassionately. The mean daily dose of tacrolimus was less in the intolerance (Int) patients throughout the study: 0.22 versus 0.17 mg/kg at 1 week and 0.14 versus 0.11 mg/kg at 24 months in rejection (Rej) and Int patients, respectively. Mean blood levels paralleled dosing in both groups, but were greater in the Rej patients (10.7 v 8.3 ng/mL at 18 months). Kaplan-Meier estimates of patient and graft survival were similar in the two groups. Patient survival rates were 80.1% and 81.5%, and graft survival rates were 72.7% and 73.9% at 24 months in the Rej and Int patients, respectively. Most adverse events occurred with a similar incidence in the two groups. Those with a 4% or greater incidence were fever, viral hepatitis, and pneumonia. The incidence of sepsis, gastrointestinal hemorrhage, kidney failure, and convulsion was greater in the Int group. The incidence of abnormal liver function test results, hyperglycemia, headache, and abnormal kidney function was greater in the Rej group. Mean liver function test results decreased with time postrescue in both groups. Mean serum creatinine level increased from baseline to 18 months postrescue in both groups (1.44 to 1.51 mg/dL for Int patients, 1.14 to 1.48 mg/dL for Rej patients). We conclude tacrolimus is safe and effective rescue in liver transplant recipients with rejection or CyA intolerance.


Anti-ulcerogenic activity of the methanol root bark extract of Cochlospermum planchonii (Hook f).
Cochlospermum planchonii (Hook f) is a common medicinal plant used in Nigeria traditional medicine for treatment of different ailments including ulcers. The anti ulcer activity of the root bark methanol extract of Cochlospermum planchonii was evaluated using different [ethanol, acetylsalicylic acid (aspirin), cold/restraint stress and pyloric ligation/histamine - induced ulcers and acid production] ulcerogenic models in rats at the doses of 250, 500, and 1000 mg/kg body weight using cimetidine (100 mg/kg) as a standard reference drug. The different doses of the extract and the reference drug significantly (p < 0.01) decreased all the ulcer parameters in a dose dependent manner in all the models used. The total number of ulcers were significantly (p < 0.05) decreased. The ulcer index was significantly (p < 0.004) reduced by the extract. Similarly, the percentage ulcer preventive index was also increased from 0% in the negative control up to 93.2% at the dose of 1000 mg/kg, while the percentage ulcer severity was dose dependently reduced by the extract. Furthermore, the extract significantly (p < 0.02) decreased free gastric HCl and total gastric acid. In conclusion, Cochlospermum planchonii methanolic root bark extract showed significant antiulcer activity in this study which may be as a result of its cytoprotective, antioxidant or antisecretory properties.


Trunk position influences the kinematics, kinetics, and muscle activity of the lead lower extremity during the forward lunge exercise.
Experimental laboratory study. To examine how a change in trunk position influences the kinematics, kinetics, and muscle activity of the lead lower extremity during the forward lunge exercise. Altering the position of the trunk during the forward lunge exercise is thought to affect the muscular actions of the lead lower extremity. However, no studies have compared the biomechanical differences between the traditional forward lunge and its variations. Ten healthy adults (5 males, 5 females; mean age +/- SD, 26.7 +/- 3.2 years) participated. Lower extremity kinematics, kinetics, and surface electromyographic (EMG) data were obtained while subjects performed 3 lunge exercises: normal lunge with the trunk erect (NL), lunge with the trunk forward (LTF), and lunge with trunk extension (LTE). A 1-way analysis of variance with repeated measures was used to compare lower extremity kinematics, joint impulse (area under the moment-time curve), and normalized EMG (highest 1-second window of activity for selected lower extremity muscles) among the 3 lunge conditions. During the LTF condition, significant increases were noted in peak hip flexion angle, hip extensor and ankle plantar flexor impulse, as well as gluteus maximus and biceps femoris EMG (P<.015) when compared to the NL condition. During the LTE condition, a significant increase was noted in peak ankle dorsiflexion and a significant decrease was noted in peak hip flexion angle (P<.015) compared to the NL condition. Performing a lunge with the trunk forward increased the hip extensor impulse and the recruitment of the hip extensors. In contrast, performing a forward lunge with the trunk extended did not alter joint impulse or activation of the lower extremity musculature. Therapy, level 5.


Multiparametric Optical Bioimaging Reveals the Fate of Epoxy Crosslinked Biomeshes in the Mouse Subcutaneous Implantation Model.
Biomeshes based on decellularized bovine pericardium (DBP) are widely used in reconstructive surgery due to their wide availability and the attractive biomechanical properties. However, their efficacy in clinical applications is often affected by the uncontrolled immunogenicity and proteolytic degradation. To address this issue, we present here in vivo multiparametric imaging analysis of epoxy crosslinked DBPs to reveal their fate after implantation. We first analyzed the structure of the crosslinked DBP using scanning electron microscopy and evaluated proteolytic stability and cytotoxicity. Next, using combination of fluorescence and hypoxia imaging, X-ray computed microtomography and histology techniques we studied the fate of DBPs after subcutaneous implantation in animals. Our approach revealed high resistance to biodegradation, gradual remodeling of a surrounding tissue forming the connective tissue capsule and calcification of crosslinked DBPs. These changes were concomitant to the development of hypoxia in the samples within 3 weeks after implantation and subsequent induction of angiogenesis and vascularization. Collectively, presented approach provides new insights on the transplantation of the epoxy crosslinked biomeshes, the risks associated with its applications in soft-tissue reconstruction and can be transferred to studies of other types of implants.


Experience of companionship among family caregivers of persons with dementia: A qualitative study.
We examined how caregivers experienced the influence of dementia on their relationships with afflicted family members. Family caregivers (n = 15; 11 women and four men; age 39-92 years) of people with dementia participated in semi-structured interviews. The data were analyzed according to Kvale and Brinkman. The analysis identified one overarching theme, experiences of companionship, and four subthemes, namely experiences of loss and loneliness; role change; communication alteration; and caring considerations and coping resources. The caregivers described their companionship with the family member, including warm feelings of reciprocity, as well as contradictory feelings, such as feelings of being burdened. They expressed a desire to continue caring for their relative and emphasized the positive aspects of their relationship. Knowledge about dementia, together with a good relationship with their ill family member, facilitated the caring role. These results highlight the importance of receiving information about dementia-related challenges and the implications of being a caregiver.


Safety Assessment of Citrus Fruit-Derived Ingredients as Used in Cosmetics.
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 80 Citrus fruit-derived ingredients, which are most frequently reported to function in cosmetics as fragrances and/or skin-conditioning agents. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. Industry should use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that these ingredients are safe for use in both rinse-off and leave-on cosmetic products when formulated to be non-sensitizing and non-irritating, provided that leave-on products do not contain more than 0.0015% (15 ppm) 5-methoxypsoralen (5-MOP).


Chloroperoxidase generation of singlet Delta molecular oxygen observed directly by spectroscopy in the 1- to 1.6-mum region.
The (0,0) (1)Delta(g) --> (3)Sigma(-) (g) singlet molecular oxygen chemiluminescence emission from a biological reaction system, chloroperoxidase (EC 22.214.171.124) acting on hydrogen peroxide at low pH (phosphate buffer, pH 2.85) with Cl(-) as a cosubstrate, was recorded with an ultrasensitive IR spectrometer. The strong chemiluminescence emission peak observed at 1.30 mum provides clear evidence of the enzymatic generation of (excited) singlet oxygen from peroxide in this system.


Dental and skeletal effects of palatal expansion techniques: a systematic review of the current evidence from systematic reviews and meta-analyses.
The aim was to assess the quality and to summarise the findings of the Systematic Reviews (SRs) and Meta-Analyses (MAs) on the dental and skeletal effects of maxillary expansion. Electronic and manual searches have been independently conducted by two investigators, up to February 2015. SRs and MAs on the dentoalveolar and skeletal effects of fixed expanders were included. The methodological quality was assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews). The design of the primary studies included in each SR/MA was assessed with the LRD (Level of Research Design scoring). The evidence for each outcome was rated applying a pre-determined scale. Twelve SRs/MAs were included. The AMSTAR scores ranged from 4 to 10. Two SRs/MAs included only RCTs. The current findings from SRs/MAs support with high evidence a significant increase in the short-term of maxillary dentoalveolar transversal dimensions after Rapid Maxillary Expansion (RME). The same effect is reported with moderate evidence after Slow Maxillary Expansion (SME). However, there is moderate evidence of a non-significant difference between the two expansion modalities concerning the short-term dentoalveolar effects. With both RME and SME, significant increase of skeletal transversal dimension in the short-term is reported, and the skeletal expansion is always smaller than the dentoalveolar. Even though dental relapse to some extent is present, long-term results of the dentoalveolar effects show an increase of the transversal dimension, supported by moderate evidence for RME and low evidence for SME. Skeletal long-term effects are reported only with RME, supported by very low evidence.


Mutations in TrpI binding site II that differentially affect activation of the trpBA promoter of Pseudomonas aeruginosa.
In vitro, Pseudomonas aeruginosa TrpI protein activates transcription initiation at the trpBA promoter (trpPB) and represses initiation at its own promoter (trpPI), which diverges from, and overlaps, trpPB. Indoleglycerol phosphate (InGP) reduces the TrpI concentration required for binding to its strong binding site (site I), as measured by repression of trpPI; it also facilitates activation of trpPB, presumably because it enables TrpI to bind to a weaker binding site (site II) and thereby interact with RNA polymerase. The role of site II and InGP in regulation of the two promoters was investigated by constructing site II mutants. A 2 bp substitution affected the ability of TrpI to activate trpPB, but did not significantly affect TrpI binding to site II. A more extensive (8 bp) substitution inhibited TrpI-mediated activation of trpPB and TrpI-mediated protection of site II in a DNase I footprinting assay. However, the mutation did not alter the pattern of TrpI binding observed in gel retardation experiments. In particular, a more slowly-migrating complex (Complex 2) whose appearance was correlated with TrpI binding to site II was formed equally well on a wild-type or substituted DNA fragment. Based on the mutant phenotypes, we propose that a particular sequence of protein--protein and protein--DNA interactions is required for activation of trpPB by TrpI and InGP.


Provider compliance with recommended dietary fluoride supplement protocol.
Proper dosage of dietary fluoride supplements is important for children without access to optimally fluoridated water to balance dental caries prevention and risks of dental fluorosis. Subsequent to water fluoride assay, compliance by physicians and dentists with the recommended dietary fluoride supplement dosage schedule was determined for 446 children. Approximately one third of child patients and 42% of siblings did not receive the recommended supplement dosage.


The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats.
Activation of glucagon-like peptide-1 (GLP-1) receptors improves insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide analogue with pharmacologic properties similar to the GLP-1 receptor agonist, exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in Dahl salt-sensitive (DSS) rats. DSS rats were fed low salt (LS, 0.3% NaCl) or high salt (HS, 8% NaCl) diets. HS rats were treated with vehicle, AC3174 (1.7 pmol/kg/min), or GLP-1 (25 pmol/kg/min) for 4 weeks via subcutaneous infusion. Other HS rats received captopril (150 mg/kg/day) or AC3174 plus captopril. HS rat survival was improved by all treatments except GLP-1. Systolic blood pressure (SBP) was lower in LS rats and in GLP-1, AC3174, captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p < 0.05). AC3174 plus captopril attenuated the deleterious effects of high salt on posterior wall thickness, LV mass, and the ratio of LV mass to body weight (P < or = 0.05). In contrast, GLP-1 had no effect on these cardiovascular parameters. All treatments reduced LV wall stress. GLP-1, AC3174, captopril, or AC3174 plus captopril normalized fasting insulin and HOMA-IR (P < or = 0.05). AC3174, captopril, or AC3174 plus captopril improved renal function (P < or = 0.05). Renal morphology in HS rats was associated with extensive sclerosis. Monotherapy with AC3174, captopril, or GLP-1 attenuated renal damage. However, AC3174 plus captopril produced the most effective improvement. Thus, AC3174 had antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal survival, an effect not observed with GLP-1.


Effect of CNT incorporation on PAN/PPy nanofibers synthesized by electrospinning method.
In this study, carbon nanotubes (CNTs) added polyacrylonitrile/polypyrrole (PAN/PPy) electrospun nanofibers were produced. Average diameters of the nanofibers were measured as 268 and 153 nm for 10 and 25 wt% of PPy contents, respectively. A relatively higher strain to failure values (23.3%) were observed for the low PPy content. When as-grown CNTs (1 and 4 wt%) were added into the PAN/PPy blends, disordered nanofibers were observed to form within the microstructure. To improve the interfacial properties of CNTs/PAN/PPy composites, CNTs were functionalized with H2SO4/HNO3/HCl solution. The functionalized CNTs were well dispersed within the nanofibers and aligned along the direction of nanofibers. Therefore, beads formation on nanofibers decreased. The impedance of the nanofibers was found to decrease with the PPy content and CNT addition. These nanofibers had a great potential to be used as an electrochemical actuator or a tissue engineering scaffold.


Phenotypic and molecular identification of Fonsecaea pedrosoi strains isolated from chromoblastomycosis patients in Mexico and Venezuela.
Chromoblastomycosis is a chronic granulomatous disease caused frequently by fungi of the Fonsecaea genus. The objective of this study was the phenotypic and molecular identification of F. pedrosoi strains isolated from chromoblastomycosis patients in Mexico and Venezuela. Ten strains were included in this study. For phenotypic identification, we used macroscopic and microscopic morphologies, carbohydrate assimilation test, urea hydrolysis, cixcloheximide tolerance, proteolitic activity and the thermotolerance test. The antifungal activity of five drugs was evaluated against the isolates. Molecular identification was performed by sequencing the internal transcribed spacer (ITS) ribosomal DNA regions of the isolated strains. The physiological analysis and morphological features were variable and the precise identification was not possible. All isolates were susceptible to itraconazole, terbinafine, voriconazole and posaconazole. Amphotericin B was the least effective drug. The alignment of the 559-nucleotide ITS sequences from our strains compared with sequences of GenBank revealed high homology with F. pedrosoi (EU285266.1). In this study, all patients were from rural areas, six from Mexico and four from Venezuela. Ten isolates were identified by phenotypic and molecular analysis, using ITS sequence and demonstrated that nine isolates from Mexico and Venezuela were 100% homologous and one isolate showed a small genetic distance.


From insecure to secure employment: changes in work, health, health related behaviours, and sickness absence.
To determine whether change in employment status (from fixed term to permanent employment) is followed by changes in work, health, health related behaviours, and sickness absence. Prospective cohort study with four year follow up. Data from 4851 (710 male, 4141 female) hospital employees having a fixed term or permanent job contract on entry to the study were collected at baseline and follow up. At baseline, compared to permanent employees, fixed term employees reported lower levels of workload, job security, and job satisfaction. They also reported greater work ability. All fixed term employees had a lower rate of medically certified sickness absence at baseline. Baseline rate ratios for those who remained fixed term were 0.64 (95% CI 0.55 to 0.75), and were 0.50 (95% CI 0.34 to 0.75) for those who later became permanent. Continuous fixed term employment was not associated with changes in the outcome measures. Change from fixed term to permanent employment was followed by an increase in job security, enduring job satisfaction, and increased medically certified sickness absence (compared to permanent workers rate ratio 0.96 (95% CI 0.80 to 1.16)). Other indicators of work, health, and health related behaviours remained unchanged. Receiving a permanent job contract after fixed term employment is associated with favourable changes in job security and job satisfaction. The corresponding increase in sickness absence might be due to a reduction in presenteeism and the wearing off of health related selection.


Cameron lesions: an often overlooked cause of iron deficiency anaemia in patients with large hiatal hernias.
Cameron lesions are linear gastric ulcers or erosions on the mucosal folds at the diaphragmatic impression in patients with a large hiatal hernia. The lesions are associated with occult bleeding and development of chronic iron deficiency anaemia, but are often overlooked during routine endoscopy. We present two patients with known hiatal hernias in who repeated endoscopic examinations had not been able to identify a source of bleeding. In both cases, typical Cameron lesions were found either by repeat gastroscopy or by capsule endoscopy. Treatment with high-dose proton pump inhibitor and iron supplement was initiated.


Tracheobroncopathia osteochondroplastica: Three case reports with literature review.
Tracheobroncopathia osteochondroplastica (TO) is a benign disease of the large airways seen very rarely. It is characterized by 1-3 mm sized ossified nodular lesions in submucosa. Its etiology is unclear, but it is stated that malignancy, chronic inflammation, amyloidosis, and genetic factors might have an effect on it. It was first described by Wilks in a 38-year-old man diagnosed with tuberculosis in 1857. Generally, patients are asymptomatic and TO is diagnosed incidentally. But symptoms become significant with infections and obstruction in tracheabronchial tree. Generally chest radiography is normal, so thorax computed tomography can be remarkable in diagnosis of TO. Besides, final diagnosis can be established by viewing ossified nodules in trachea and bronchus through the fiberoptic bronchoscopy. Amyloidosis, tuberculosis, sarcoidosis, bronchial carcinoma, and tracheobronchial calcinosis must be remembered in differential diagnosis. Also ossifications in submucosa and proof of bone marrow in histopathological examinations are important in diagnosis of TO. Mostly palliative treatment is performed to the symptoms . We want the clinicians to keep in mind for this very rarely seen tracheal disease with three case reports.


Microbial adhesion of Cryptosporidium parvum sporozoites: purification of an inhibitory lipid from bovine mucosa.
Cryptosporidium parvum is a protozoan pathogen of humans and livestock worldwide. Its ability to infect a wide range of species raises questions as to the involvement of a specific host cell receptor for parasite-host recognition. To investigate the mechanism of parasite-host cell recognition, we have developed an in vitro cell suspension binding assay to investigate adhesion of C. parvum sporozoites to host cells. Morphologic features of binding events observed with this assay were identical to those described in natural infections. Glycoconjugates, Madin Darby bovine kidney (MDBK) cell fractions, and plasma membrane vesicles (PMVs) were screened for their ability to block binding of sporozoites to MDBK cells. Mucins, MDBK cell fractions, and PMVs exhibited dose-dependent inhibition of sporozoite binding. The major inhibitory fraction from MDBK cells was found to be insoluble in aqueous medium, nonsaponifiable, and lacking carbohydrate moieties, nitrogen, and phosphorus. Its inhibitory effect was resistant to heat, protease digestion, and glycosidase treatment, suggesting that the inhibitory activity is a lipid or a lipid-like component. The inhibitory activity was purified from MDBK cells, and in larger amounts from bovine small intestinal mucosa, by organic solvent extraction, semipreparative high-pressure liquid chromatography, and preparative high-performance thin-layer chromatography. Biochemical analyses, thin-layer chromatography staining techniques, mass spectrometry, and elemental analysis were used to partially characterize the purified lipid. These results indicate that a host intestinal lipid(s) or a lipid-like component(s) may play an important role in the early stages of host cell invasion by C. parvum.


Functional tagging of regulatory elements in the plant genome.
In comparison with animals, relatively few plant genes have been identified that have been shown to be under organ-, tissue- or cell-type-specific regulation. In this paper, we describe how the beta-glucuronidase (GUS) reporter gene (gusA or uidA), fused to a weak promoter (a truncated (-90 bp) CaMV35S promoter), can be used to identify tissue-specific markers in transgenic tobacco plants. The rationale was that the expression of gusA would be determined primarily by position effect. Quantitative analysis revealed that, of 184 -90-gus transgenic plants, 73% exhibited gusA gene activation in leaf tissue, and the level of GUS enzyme activity varied over a 300-fold range within the population. In comparison, transformation with a promoterless gusA gene resulted in GUS expression in 78% of all plants analyzed (in leaf and/or root) and expression levels were three-fold or more lower. Qualitative GUS analysis of single locus -90-gus transformants revealed differential expression in diverse tissues. The spatial pattern of GUS activity was unique to individual transformants, was a reflection of differential gusA gene transcription, and was stably transmissible to progeny. Evidence for preferential expression in roots not only of the -90-gus, but also the promoterless gusA gene is presented. The value of the -90 bp promoter-gusA sequence, which is termed an 'interposon', as a tool both to identify native enhancer sequences in situ and to investigate position effects in plants, is discussed.


Inhibition of nicotinic acid and nicotinamide uptake into Bordetella pertussis by structural analogues.
3-Pyridine-carboxaldehyde and 3-pyridine-aldoxime were effective and specific inhibitors of the uptake of both nicotinic acid (NA) and nicotinamide (ND) by Bordetella pertussis, although neither compound inhibited the growth of the bacteria in liquid medium or the oxidation of glutamate by washed suspensions. In contrast, the following pyridine derivatives did not inhibit uptake of NA or ND: iso-NA, iso-ND, isoniazid, 6-amino-NA and 6-amino-ND, 3-acetyl-pyridine, 3-pyridyl-acetic acid, N,N-diethyl-ND and 3-pyridine-sulphonic acid. 3- Pyridyl-carbinol was inhibitory, but less so than the first listed compounds.


Shape matters: Competing mechanisms of particle shape segregation.
It is well known that granular mixtures that differ in size or shape segregate when sheared. In the past, two mechanisms have been proposed to describe this effect, and it is unclear if both exist. To settle this question, we consider a bidisperse mixture of spheroids of equal volume in a rotating drum, where the two mechanisms are predicted to act in opposite directions. We present evidence that there are two distinct segregation mechanisms driven by relative overstress. Additionally, we showed that, for nonspherical particles, these two mechanisms (kinetic and gravity) can act in different directions leading to a competition between the effects of the two. As a result, the segregation intensity varies nonmonotonically as a function of aspect ratio (AR), and, at specific points, the segregation direction changes for both prolate and oblate spheroids, explaining the surprising segregation reversal previously reported. Consistent with previous results, we found that the kinetic mechanism is dominant for (almost) spherical particles. Furthermore, for moderate aspect ratios, the kinetic mechanism is responsible for the spherical particles' segregation to the periphery of the drum, and the gravity mechanism plays only a minor role. Whereas, at the extreme values of AR, the gravity mechanism notably increases and overtakes its kinetic counterpart.


Bacillus subtilis MreB orthologs self-organize into filamentous structures underneath the cell membrane in a heterologous cell system.
Actin-like bacterial cytoskeletal element MreB has been shown to be essential for the maintenance of rod cell shape in many bacteria. MreB forms rapidly remodelling helical filaments underneath the cell membrane in Bacillus subtilis and in other bacterial cells, and co-localizes with its two paralogs, Mbl and MreBH. We show that MreB localizes as dynamic bundles of filaments underneath the cell membrane in Drosophila S2 Schneider cells, which become highly stable when the ATPase motif in MreB is modified. In agreement with ATP-dependent filament formation, the depletion of ATP in the cells lead to rapid dissociation of MreB filaments. Extended induction of MreB resulted in the formation of membrane protrusions, showing that like actin, MreB can exert force against the cell membrane. Mbl also formed membrane associated filaments, while MreBH formed filaments within the cytosol. When co-expressed, MreB, Mbl and MreBH built up mixed filaments underneath the cell membrane. Membrane protein RodZ localized to endosomes in S2 cells, but localized to the cell membrane when co-expressed with Mbl, showing that bacterial MreB/Mbl structures can recruit a protein to the cell membrane. Thus, MreB paralogs form a self-organizing and dynamic filamentous scaffold underneath the membrane that is able to recruit other proteins to the cell surface.


Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control.
Suppression of premature termination codons (PTCs) by translational readthrough is a promising strategy to treat a wide variety of severe genetic diseases caused by nonsense mutations. Here, we present two potent readthrough promoters-NVS1.1 and NVS2.1-that restore substantial levels of functional full-length CFTR and IDUA proteins in disease models for cystic fibrosis and Hurler syndrome, respectively. In contrast to other readthrough promoters that affect stop codon decoding, the NVS compounds stimulate PTC suppression by triggering rapid proteasomal degradation of the translation termination factor eRF1. Our results show that this occurs by trapping eRF1 in the terminating ribosome, causing ribosome stalls and subsequent ribosome collisions, and activating a branch of the ribosome-associated quality control network, which involves the translational stress sensor GCN1 and the catalytic activity of the E3 ubiquitin ligases RNF14 and RNF25.


Low molecular weight heparin and unfractionated heparin in the early pharmacologic management of acute coronary syndromes: a meta-analysis of randomized clinical trials.
The standard of care in Acute Coronary Syndromes (ACS) includes a full complement of antischemic and antithrombotic therapy. Although aspirin is used widely and concomitant anticoagulation is recommended, the comparative benefits of low molecular weight heparin (LMWH) and unfractionated heparin (UFH) have not been defined. A meta-analysis including all randomized clinical trials comparing LMWH and UFH for the treatment of non-ST segment elevation acute coronary syndromes was performed. Risk ratios (RR), using the DerSimonian-Laird Model, were calculated from a total of 13,320 patients. Death (RR 0.98, 95% CI 0.73-1.31), death and myocardial infarction (MI) (RR 0.86, 95% CI 0.74-1.01), death, MI, recurrent angina or revascularization (RR 0.89, 95% CI 0.74-1.07) and major hemorrhage (RR 1.01, 95% CI 0.81-1.25) occurred with similar frequencies for the anticoagulant-based strategies. Fixed dose LMWH therapy given subcutaneously compares favorably with UFH titrated to a target level of anticoagulation and should be considered a safe, effective, and clinically acceptable alternative in the early management of patients with non-ST segment elevation ACS. The superiority of LMWH preparations characterized by high in vitro factor Xa to thrombin inhibitory capacity is supported by clinic trial data but requires further investigation.


Temporal variations in the effective reproduction number of the 2014 west Africa ebola outbreak.
Background The rapidly evolving 2014 Ebola virus disease (EVD) outbreak in West Africa is the largest documented in history, both in terms of the number of people infected and in the geographic spread. The high morbidity and mortality have inspired response strategies to the outbreak at the individual, regional, and national levels. Methods to provide real-time assessment of changing transmission dynamics are critical to the understanding of how these adaptive intervention measures have affected the spread of the outbreak. Methods In this analysis, we use the time series of EVD cases in Guinea, Sierra Leone, and Liberia up to September 8, 2014, and employ novel methodology to estimate how the rate of exponential rise of new cases has changed over the outbreak using piecewise fits of exponential curves to the outbreak data. Results We find that for Liberia and Guinea, the effective reproduction number rose, rather than fell, around the time that the outbreak spread to densely populated cities, and enforced quarantine was imposed on several regions in the countries; this may indicate that enforced quarantine may not be an effective control measure. Conclusions If effective control measures are not put in place, and the current rate of exponential rise of new cases continues, we predict 4400 new Ebola cases in West Africa during the last half of the month of September, with an upper 95% confidence level of 6800 new cases.


Ghrelin induces clock gene expression in the liver of goldfish in vitro via protein kinase C and protein kinase A pathways.
The liver is the most important link between the circadian system and metabolism. As a food-entrainable oscillator, the hepatic clock needs to be entrained by food-related signals. The objective of the present study was to investigate the possible role of ghrelin (an orexigenic peptide mainly synthesized in the gastrointestinal tract) as an endogenous synchronizer of the liver oscillator in teleosts. To achieve this aim, we first examined the presence of ghrelin receptors in the liver of goldfish. Then, the ghrelin regulation of clock gene expression in the goldfish liver was studied. Finally, the possible involvement of the phospholipase C/protein kinase C (PLC/PKC) and adenylate cyclase/protein kinase A (AC/PKA) intracellular signalling pathways was investigated. Ghrelin receptor transcripts, ghs-r1a, are present in the majority of goldfish hepatic cells. Ghrelin induced the mRNA expression of the positive (gbmal1a, gclock1a) and negative (gper genes) elements of the main loop of the molecular clock machinery, as well as grev-erbα (auxiliary loop) in cultured liver. These effects were blocked, at least in part, by a ghrelin antagonist. Incubation of liver with a PLC inhibitor (U73122), a PKC activator (phorbol 12-myristate 13-acetate) and a PKC inhibitor (chelerythrine chloride) demonstrated that the PLC/PKC pathway mediates such ghrelin actions. Experiments with an AC activator (forskolin) and a PKA inhibitor (H89) showed that grev-erbα regulation could be due to activation of PKA. Taken together, the present results show for the first time in vertebrates a direct action of ghrelin on hepatic clock genes and support a role for this hormone as a temporal messenger in the entrainment of liver circadian functions.


Plug-n-play microfluidic systems from flexible assembly of glass-based flow-control modules.
In this study, we report on a simple and versatile plug-n-play microfluidic system that is fabricated from flexible assembly of glass-based flow-control modules for flexibly manipulating flows for versatile emulsion generation. The microfluidic system consists of three basic functional units: a flow-control module, a positioning groove, and a connection fastener. The flow-control module that is based on simple assembly of low-cost glass slides, coverslips, and glass capillaries provides excellent chemical resistance and optical properties, and easy wettability modification for flow manipulation. The flexible combination of the flow-control modules with 3D-printed positioning grooves and connection fasteners enables creation of versatile microfluidic systems for generating various higher-order multiple emulsions. The simple and reversible connection of the flow-control modules also allows easy disassembly of the microfluidic systems for further scale-up and functionalization. We demonstrate the scalability and controllability of flow manipulation by creating microfluidic systems from flexible assembly of flow-control modules for controllable generation of multiple emulsions from double emulsions to quadruple emulsions. Meanwhile, the flexible flow manipulation in the flow-control module provides advanced functions for improved control of the drop size, and for controllable generation of drops containing distinct components within multiple emulsions to extend the emulsion structure. Such modular microfluidic systems provide flexibility and versatility to flexibly manipulate micro-flows for enhanced and extended applications.


Effects of denervation on the glycogen content and on the activities of enzymes of glucose and glycogen metabolism in rat diaphragm muscle.
1. Changes in the content and concentration of glycogen and in the activity of a number of enzymes involved in glucose and glycogen metabolism were studied in the rat hemidiaphragm after unilateral denervation. 2. After nerve section the tissue hypertrophies; this hypertrophy is said to be confined to the smaller red fibres and not to the white. 3. The total hexokinase activity increases, whereas that of total glycogen phosphorylase decreases. The specific activity of phosphorylase a, determined after Halothane anaesthesia, remains fairly constant. 4. In fed animals the denervated tissue stores less glycogen, but in the early stages its glycogen content does not fall on starvation. 5. The effect of denervation on the specific activities of several other characteristically white-fibre enzymes are not consistent with the response of glycogen phosphorylase; the increase in content of glyceraldehyde 3-phosphate dehydrogenase and lactate dehydrogenase is thought to be related to proliferation of the sarcoplasmic reticulum. 6. The ratio of lactate dehydrogenase M/H subunits increases at the height of the hypertrophy, but then declines as the mass of the tissue falls. 7. The chronology of these changes in enzyme activities suggests a multiplicity of distinct responses after nerve section not consistent with any one model, either specific fibre development or reversion to de-differentiated, foetal-type metabolism.


Influence of long-term exposure to simulated acid rain on development, reproduction and acaricide susceptibility of the carmine spider mite, Tetranychus cinnabarinus.
Development, reproduction and acaricide susceptibility of Tetranychus cinnabarinus (Boisduvals) (Acari: Tetranychidae) were investigated after long-term (about 40 generations) exposure to various levels of acid rain; pH 2.5, 3.0, 4.0, and 5.6. Deionized water (pH 6.8) served as a control. The mites were reared on eggplant leaves at 28 degrees C, 80%RH and a photoperiod of 14:10 (L:D) in the laboratory. The results showed that the duration of the immature stage was significantly affected by acid rain exposure. The shortest duration (8.90 days) was recorded for populations exposed to pH 5.6 acid rain, while the longest duration (9.37 days) occurred after exposure to pH 2.5 acid rain. Compared with the control population, adult longevity was shortened with an increase in acidity. Similarly, the oviposition duration was also shortened by an increase in acidity. Statistically, female fecundity did not differ significantly between pH 5.6, pH 4.0 and control populations, but did differ significantly between the control population and those exposed to pH 2.5 and pH 3.0 acid rain. This suggested that the mite suffered reproductive defects after long-term exposure to acid rain with higher acidity (pH 2.5 and 3.0). The intrinsic rate of increase among different populations was not significantly affected, but the net reproductive rate of populations exposed to pH 2.5 and 3.0 acid rain was significantly less than pH 4.0, 5.6, and control populations. Bioassay results showed that after long-term exposure to acid rain, susceptibility of the mites to two acaricides, dichlorvos and fenpropathrin, did not change significantly.


[Effect of antioxidants and complexons on the stability of the microbiological standard for mycoheptin].
Stability is one of the most important indices of the quality of antibiotic microbiological standards. At present the expiry date of the mycoheptin standard (a specially purified preparation) is 1 year when stored in sealed ampoules in an inert gas at a temperature of -20 degrees C. To prolong the expiry date of the standard the effect of various antiohidants and complexons on its stability was studied with the method of "accelerated aging". Sodium hexametaphosphate and Trilon B were tested as complexing agents and propyl gallate, ionol, N-phenyl-2-napththyl amine, mannitol and their mixtures were tested as antioxidants. The substances were applied in an amount of 3 per cent of the antibiotic weight. The favourable effect of the complexons on mycoheptin stability was shown. Their stabilizing effect was potentiated by addition of certain antioxidants.