Geospatial analysis on the distributions of tobacco smoking and alcohol drinking in India.
Tobacco smoking and binge alcohol drinking are two of the leading risk factors for premature mortality worldwide. In India, studies have examined the geographic distributions of tobacco smoking and alcohol drinking only at the state-level; sub-state variations and the spatial association between the two consumptions are poorly understood. We used data from the Special Fertility and Mortality Survey conducted in 1998 to examine the geographic distributions of tobacco smoking and alcohol drinking at the district and postal code levels. We used kriging interpolation to generate smoking and drinking distributions at the postal code level. We also examined spatial autocorrelations and identified spatial clusters of high and low prevalence of smoking and drinking. Finally, we used bivariate analyses to examine the spatial correlations between smoking and drinking, and between cigarette and bidi smoking. There was a high prevalence of any smoking in the central and northeastern states, and a high prevalence of any drinking in Himachal Pradesh, Arunachal Pradesh, and eastern Madhya Pradesh. Spatial clusters of early smoking (started smoking before age 20) were identified in the central states. Cigarette and bidi smoking showed distinctly different geographic patterns, with high levels of cigarette smoking in the northeastern states and high levels of bidi smoking in the central states. The geographic pattern of bidi smoking was similar to early smoking. Cigarette smoking was spatially associated with any drinking. Smoking prevalences in 1998 were correlated with prevalences in 2004 at the district level and 2010 at the state level. These results along with earlier evidence on the complementarities between tobacco smoking and alcohol drinking suggest that local public health action on smoking might also help to reduce alcohol consumption, and vice versa. Surveys that properly represent tobacco and alcohol consumptions at the district level are recommended.


Pre-slaughter, slaughter and post-slaughter defects of skins and hides at the Sheba Tannery and Leather Industry, Tigray region, northern Ethiopia.
Skins and hides are perishable resources that can be damaged by parasitic diseases and human error, which result in downgrading or rejection. This study was conducted to identify defect types and to determine their prevalence in pickled sheep and wet blue goat skins and wet blue hides. Each selected skin or hide was examined for defects in natural light and the defects were graded according to established quality criteria in Ethiopian standard manuals. Major defects were captured by digital photography. The major pre-slaughter defects included scratches (64.2%), cockle (ekek) (32.8%), wounds or scars (12.6%), lesions from pox or lumpy skin disease (6.1%), poor substance (5%), branding marks (2.3%) and tick bites (1.5%). The presence of grain scratches in wet blue hides (76.3%) was significantly higher than in pickled sheep (67.2%) and wet blue goat (59.1%) skins. The major slaughter defects included flay cuts or scores, holes, poor pattern and vein marks, with a higher occurrence in wet blue goat skins (28.7%; P < 0.001) than in wet blue hides (22.8%) and pickled sheep skins (11.1%). The most prevalent postslaughter defects were grain cracks (14.9%), hide beetle damage (8%), damage caused by heat or putrefaction (3.7%) and machine-induced defects (0.5%). Grain cracks (27.04%) and hide beetle damage (13.9%) in wet blue goat skins were significantly more common than in wet blue hides and pickled sheep skins. These defects cause depreciation in the value of the hides and skins. Statistically significant (P < 0.001) higher rejection rates were recorded for wet blue hides (82.9%) than for pickled sheep skins (18.3%) and wet blue goat skins (8.5%). Improved animal health service delivery, effective disease control strategies and strong collaboration between stakeholders are suggested to enhance the quality of skins and hides.


Ontogeny of somatic angiotensin-converting enzyme.
Angiotensin-converting enzyme or kininase II (ACE-KII) plays a central role in the control of circulating and tissue levels of angiotensin II and kinins. Both peptides have been implicated in the regulation of renal function and growth during normal development. We tested the hypothesis that the developing rat kidney expresses ACE-KII mRNA transcripts and the active enzyme and evaluated whether the developmental expression of the ACE-KII gene is related to changes in circulating angiotensin II and tissue kallikrein. ACE-KII mRNA and enzymatic activity were low in the newborn kidney; peak expression occurred on days 15 and 20 of postnatal life (16-fold versus day 1). In extrarenal tissues, ACE-KII activity and mRNA levels were also low during the newborn period in the following order of abundance: lung > kidney > aorta > heart. The lung showed a higher age-related increase in active ACE-KII and mRNA abundance (15-fold) than heart and aorta (activity, 3- to 4-fold; mRNA, 6- to 10-fold). The developmental profile of ACE-KII correlated temporally with changes in circulating angiotensin II and tissue kallikrein. Plasma angiotensin II levels were 2.5-fold higher in newborn than adult rats, whereas renal and extrarenal kallikrein-like activity increased twofold to fivefold from birth to adulthood. These results demonstrate that the ACE-KII gene is developmentally regulated in a tissue-specific manner. Tissue kinin generation and degradation, reflected by kallikrein and ACE-KII activities, are coordinately regulated during development, whereas circulating angiotensin II and tissue ACE-KII change in a reciprocal manner.(ABSTRACT TRUNCATED AT 250 WORDS)


Bone marrow transplantation in newborn rats with mucopolysaccharidosis type VI: biochemical, pathological, and clinical findings.
Mucopolysaccharidosis type VI (MPS VI) is the lysosomal storage disorder caused by the deficient activity of arylsulfatase B (ASB). In this study, we evaluated bone marrow transplantation (BMT) for the treatment of MPS VI and the effects of irradiation on the survival and engraftment of bone marrow-transplanted neonatal rats. One- to 2-day-old MPS VI rats were injected with normal bone marrow after irradiation with 200, 400, or 800 cGy. Ninety percent of the animals receiving a single dose of 200 cGy (n=30) survived the procedure, whereas irradiation with 400 cGy (n=23) or 800 cGy (n=12) resulted in significant mortality (78% and 100%, respectively). Engraftment was monitored by determining ASB activities in peripheral white blood cells and by Y chromosome in situ hybridization analysis. Fifty-two percent of the animals from the 200-cGy group engrafted for up to 8 months after BMT; among the five animals that survived the 400-cGy dose, all engrafted. In comparison, only 20% of nonirradiated animals engrafted at low levels. Of the 24 engrafted animals that were monitored for 8 months after BMT, clinical and/or radiographic improvements were noted in only one (BMT animal 3). Enzymatic analysis revealed that the ASB activities in the reticuloendothelial organs of this animal, as well as two other engrafted but clinically unimproved animals (BMT animals 1 and 2), were normal or near normal; correspondingly, the glycosaminoglycan levels in these organs were significantly reduced. Consistent with the clinical and biochemical observations, light and electron microscopic findings were more improved in BMT animal 3 as compared with BMT animals 1 and 2, although a reduction of storage was evident in each of these transplant recipients, particularly in the trachea and aorta, two tissues that are characteristic sites of pathology in human patients. These results indicate that BMT in newborn MPS VI patients may prevent many of the pathological and clinical findings in this disorder, but is likely to have very limited and unpredictable effects on the skeletal abnormalities.


Depth-resolved measurement of mucosal microvascular blood content using low-coherence enhanced backscattering spectroscopy.
Low-coherence enhanced backscattering (LEBS) spectroscopy is a light scattering technique which uses partial spatial coherence broadband illumination to interrogate the optical properties at sub-diffusion length scales. In this work, we present a post-processing technique which isolates the hemoglobin concentration at different depths within a sample using a single spectroscopic LEBS measurement with a fixed spatial coherence of illumination. We verify the method with scattering (spectralon reflectance standard and polystyrene microspheres) and absorbing (hemoglobin) phantoms. We then demonstrate the relevance of this method for quantifying hemoglobin content as a function of depth within biological tissue using the azoxymethane treated animal model of colorectal cancer.


Identification and characterization of sporulation gene spoVS from Bacillus subtilis.
We report the identification and characterization of an additional sporulation gene from Bacillus subtilis called spoVS, which is induced early in sporulation under the control of sigma H. We show that spoVS is an 86-codon-long open reading frame and is capable of encoding a protein of 8,796 Da which exhibits little similarity to other proteins in the databases. Null mutations in spoVS have two contrasting phenotypes. In otherwise wild-type cells they block sporulation at stage V, impairing the development of heat resistance and coat assembly. However, the presence of a spoVS mutation in a spoIIB spoVG double mutant (which is blocked at the stage [II] of polar septation) acts as a partial suppressor, allowing sporulation to advance to a late stage. The implications of the contrasting phenotypes are discussed in the context of the formation and maturation of the polar septum.


Calibration of optical tweezers based on an autoregressive model.
The power spectrum density (PSD) has long been explored for calibrating optical tweezers stiffness. Fast Fourier Transform (FFT) based spectral estimator is typically used. This approach requires a relatively longer data acquisition time to achieve adequate spectral resolution. In this paper, an autoregressive (AR) model is proposed to obtain the Spectrum Density using a limited number of samples. According to our method, the arithmetic model has been established with burg arithmetic, and the final prediction error criterion has been used to select the most appropriate order of the AR model, the power spectrum density has been estimated based the AR model. Then, the optical tweezers stiffness has been determined with the simple calculation from the power spectrum. Since only a small number of samples are used, the data acquisition time is significantly reduced and real-time stiffness calibration becomes feasible. To test this calibration method, we study the variation of the trap stiffness as a function of the parameters of the data length and the trapping depth. Both of the simulation and experiment results have showed that the presented method returns precise results and outperforms the conventional FFT method when using a limited number of samples.


Bacillus paralicheniformis sp. nov., isolated from fermented soybean paste.
An isolate of a Gram-stain-positive, facultatively anaerobic, motile, rod-shaped, endospore-forming bacterium was recovered from soybean-based fermented paste. Phylogenetic analysis of the 16S rRNA gene indicated that the strain was most closely related to Bacillus sonorensis KCTC-13918T (99.5 % similarity) and Bacillus licheniformis DSM 13T (99.4 %). In phenotypic characterization, the novel strain was found to grow at 15–60 °C and to tolerate up to 10 % (w/v) NaCl. Furthermore, the strain grew in media with pH 6–11 (optimal growth at pH 7.0–8.0). The predominant cellular fatty acids were anteiso-C15 : 0 (37.7 %) and iso-C15 : 0 (31.5 %). The predominant isoprenoid quinone was menaquinone 7 (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid. A draft genome sequence of the strain was completed and used for phylogenetic analysis. Phylogenomic analysis of all published genomes of species in the B. licheniformis group revealed that strains belonging to B. licheniformis clustered into two distinct groups, with group 1 consisting of B. licheniformis DSM 13T and 11 other strains and group 2 consisting of KJ-16T and four other strains. The DNA G+C content of strain KJ-16T was 45.9 % (determined from the genome sequence). Strain KJ-16T and another strain from group 2 were subsequently characterized using a polyphasic taxonomic approach and compared with strains from group 1 and another closely related species of the genus Bacillus. Based upon the consensus of phylogenetic and phenotypic analyses, we conclude that this strain represents a novel species within the genus Bacillus, for which the name Bacillus paralicheniformis sp. nov. is proposed, with type strain KJ-16T ( = KACC 18426T = NRRL B-65293T).


Two new giant pill-millipede species of the genus Zoosphaerium endemic to the Bemanevika area in northern Madagascar (Diplopoda, Sphaerotheriida, Arthrosphaeridae).
Madagascar is one of the world's most important hotspots of biodiversity and a center for localized endemism. Among the highly endemic faunal elements are the giant pill-millipedes, order Sphaerotheriida, which are severely understudied in Madagascar. Here we provide descriptions of two new species of endemic giant-pill millipedes of the genus Zoosphaerium Pocock, 1895: Zoosphaerium bemanevika n. sp. and Zoosphaerium minutus n. sp.. Zoosphaerium bemanevika n. sp. belongs to the Z. coquerelianum species-group, while Z. minutus n. sp. is not assignable to a species-group. An updated key to the 19 species of the Z. coquerelianum group is provided. Zoosphaerium minutus n. sp. has a body length of <20 mm and thus is the smallest known member of the genus, being of similar size as the larger species of Microsphaerotherium Wesener & VandenSpiegel, 2007. Both species are described utilizing drawings, scanning electron microscopy and genetic barcoding based on the mitochondrial COI gene. MicroCT imaging is applied to study internal morphology non-destructively and in situ, allowing for a reconstruction of the head skeleton. Our results show that females of Z. bemanevika n. sp. exhibit island gigantism. The two newly described species are not closely related to one another but each to different species from the Marojejy Mountain and the lowland rainforest of the east coast. Both species occur sympatrically as microendemics in small patches of humid evergreen forest near Bemanevika in northern Madagascar, an only recently protected area that represents a Malagasy center of endemism.


Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial.
Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 μg/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.


Millennium Development Goals progress: a perspective from sub-Saharan Africa.
Sub-Saharan Africa is a highly diverse geo-political region. Any brief discussion of the progress made over the last 15 years towards the Millennium Development Goals (MDGs) will therefore not do justice to the true complexity of context and events. Our focus will be MDG4-to reduce child mortality by 66% from 1990 levels. We will touch briefly on MDG1, to eradicate extreme poverty and hunger, MDG2, to achieve universal primary education, and MDG5, to improve maternal health, which are inextricably linked with child well-being. We will also draw on an eclectic mix of additional global indicators. Acknowledging the limitations of this approach, we first offer a summary of expected progress and then point to debates on future goals.


Transplacental Transmission of Pemphigus Herpetiformis in the Setting of Maternal Lymphoma.
Pemphigus herpetiformis (PH) is characterized by grouped vesicular or papular pruritic lesions with histologic and immunopathologic features of pemphigus. PH can manifest at any age, and paraneoplastic cases have been reported. We describe a healthy boy born with acral crateriform erosions of the hands and feet whose 35-year-old mother had similar lesions. Biopsies from both patients were most consistent with PH. The mother was diagnosed with high-grade B-cell non-Hodgkin lymphoma and began chemotherapy with dexamethasone, and her lesions quickly improved. The infant had no additional lesions after 3 weeks of age and his acral erosions healed. To our knowledge, this is the first report of a diagnosis of PH in an infant and the first case of transplacental transmission of PH. This is also the first report of paraneoplastic PH in lymphoma. This case adds to the growing differential diagnosis of skin disease in postpartum women and their neonates.


Occurrence of RD149 and RD152 deletions in Mycobacterium tuberculosis strains from Pakistan.
Central Asian Strain 1 (CAS1) is the predominant Mycobacterium tuberculosis genotype in Pakistan. The occurrence of deletions in regions of differences (RDs) among CAS1 and other predominant genogroups in the country were investigated. Using stratified random sampling, 235 M. tuberculosis (185 pulmonary; 50 extrapulmonary) strains were selected from 926 previously spoligotyped isolates, including 171 CAS strains (133 CAS1 (ST26), 38 CAS subfamily), 8 Beijing isolates, 47 isolates belonging to other previously defined ("Other") clusters, and 9 previously undefined Unique isolates. Commonly reported RD deletions, RD1, RD750, RD207, RD149, RD152, RD105, RD150, RD142 and RD181, were investigated using a PCR-based method. Deletions in RDs 750, 149 and 152 were identified among CAS strains, and in RDs 207, 149, 152, 105, 150, 142 and 181 in Beijing isolates. CAS1 strains showed more frequent RD149 deletions compared with CAS subfamily strains (p = 0.036), and more frequent RD152 deletions compared with "Other" clusters (p = 0.003). RD149 and RD152 deletions were more frequent in Beijing isolates compared with CAS1 strains (p < 0.001). Concurrent RD149 and RD152 deletions were more frequent in CAS1 compared with "Other" clusters (p < 0.001) and in Beijing strains compared with CAS1 (p < 0.001). No significant difference was detected in RD deletion patterns between pulmonary and extra pulmonary isolates. Higher frequencies of RD149 and RD152 deletions and of concurrent RD149 and RD152 deletions were found in CAS1 and Beijing strains compared with CAS subfamilies, "Other" clusters and Unique strains. No association between these deletions and disease presentation, pulmonary or extrapulmonary tuberculosis, was observed.


Upwelling intensity modulates the fitness and physiological performance of coastal species: Implications for the aquaculture of the scallop Argopecten purpuratus in the Humboldt Current System.
Understanding how marine species cope with the natural environmental variability of their native habitats will provide significant information about their sensitivity to the potential environmental changes driven by climate change. In particular, marine species inhabiting upwelling ecosystems are experiencing low seawater temperatures, as well as, acidic and low oxygen conditions as a consequence of the nature of the deep upwelled waters. Our study is focused on one of the most important socio-economical resources of the Humboldt Current System (HCS): the scallop Argopecten purpuratus which has been historically subjected to intensive aquaculture in areas influenced by upwelling processes. Here, a long-term field experiment was performed to understand how tolerant and well-locally-adapted is A. purpuratus to upwelling conditions by studying a set of fitness, physiological, and biomineralogical traits. Stronger upwelling generated a minor water column stratification, with lower temperatures, pH, and oxygen conditions. On the contrary, as upwelling weakened, temperature, pH, and oxygen availability increased. Finally, upwelling intensity also determined the number, duration, and intensity of the cooling and de-oxygenation events occurring in A. purpuratus habitat, as well as, the food availability (chlorophyll-a concentration, Chl-a). Physiologically, A. purpuratus was able to cope with stressful environmental conditions imposed by higher upwelling intensities by enhancing its metabolic and calcification rates, as well, producing higher concentrations of the shell organic matter. These physiological changes impacted the total energy budget, which was highly dependent on Chl-a concentration, and revealed important traits trade-offs with significant fitness costs (higher mortalities emerged when longer and more intense upwelling events succeed). Our study increases the knowledge about the physiological performance and tolerance of this important resource to the ocean acidification and ocean-deoxygenation imposed by variable upwelling intensities, as well as, its potential vulnerability under future changing conditions driven by a potential upwelling intensification.


NMR structure and backbone dynamics of a concatemer of epidermal growth factor homology modules of the human low-density lipoprotein receptor.
The ligand-binding region of the low-density lipoprotein (LDL) receptor is formed by seven N-terminal, imperfect, cysteine-rich (LB) modules. This segment is followed by an epidermal growth factor precursor homology domain with two N-terminal, tandem, EGF-like modules that are thought to participate in LDL binding and recycling of the endocytosed receptor to the cell surface. EGF-A and the concatemer, EGF-AB, of these modules were expressed in Escherichia coli. Correct protein folding of EGF-A and the concatemer EGF-AB was achieved in the presence or absence of calcium ions, in contrast to the LB modules, which require them for correct folding. Homonuclear and heteronuclear 1H-15N NMR spectroscopy at 17.6 T was used to determine the three-dimensional structure of the concatemer. Both modules are formed by two pairs of short, anti-parallel beta-strands. In the concatemer, these modules have a fixed relative orientation, stabilized by calcium ion-binding and hydrophobic interactions at the interface. 15N longitudinal and transverse relaxation rates, and [1H]-15N heteronuclear NOEs were used to derive a model-free description of the backbone dynamics of the molecule. The concatemer appears relatively rigid, particularly near the calcium ion-binding site at the module interface, with an average generalized order parameter of 0.85+/-0.11. Some mutations causing familial hypercholesterolemia may now be rationalized. Mutations of D41, D43 and E44 in the EGF-B calcium ion-binding region may affect the stability of the linker and thus the orientation of the tandem modules. The diminutive core also provides little structural stabilization, necessitating the presence of disulfide bonds. The structure and dynamics of EGF-AB contrast with the N-terminal LB modules, which require calcium ions both for folding to form the correct disulfide connectivities and for maintenance of the folded structure, and are connected by highly mobile linking peptides.


(A gamma delta beta) thalassaemia: similarity of phenotype in four different molecular defects, including one newly described.
Globin gene mapping of DNA from families with (A gamma delta beta) thalassaemia has revealed a previously unreported gene deletion responsible for this condition. The deletion removes the A gamma, delta and beta genes and while its 5' end is in a similar position to that described in a previous deletion of this type, the 3' ends of the two deletions are quite different. In addition we have observed further examples of two other previously described deletions which result in this disorder. Phenotypic comparisons of families with (A gamma delta beta) thalassaemia, in which the molecular basis has been defined, show a remarkable similarity among the four different deletion defects, with important implications with regard to the mechanism by which deletions allow the continued expression of gamma genes.


Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance.
Toll-like receptor 4 (TLR4) has a key role in innate immunity by activating an inflammatory signaling pathway. Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. However, current evidence suggests that FFAs do not directly bind to TLR4, but an endogenous ligand for TLR4 remains to be identified. Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. We further found that FetA, through its terminal galactoside moiety, directly binds the residues of Leu100-Gly123 and Thr493-Thr516 in Tlr4. FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. This may position FetA as a new therapeutic target for managing insulin resistance and type 2 diabetes.


Esophageal A-ring is associated with the severity of gastroesophageal reflux.
The esophageal A-ring (EAR) is an anatomic finding appreciated on videofluoroscopic esophagram (VFE) at the junction of the tubular esophagus and esophageal vestibule. EARs are appreciated on a small subset (5%) of VFEs. We hypothesize that EARs represent a compensatory mechanism to protect against gastroesophageal reflux (GER). To evaluate the association between EAR and GER. Case control study. All persons having undergone ambulatory pH testing with an EAR identified on VFE between November 1, 2014 and June 30, 2014 were identified. All cases were matched to controls by age, gender, and the presence/absence of hiatal hernia. Subjective dysphagia severity was assessed with the EAT10 and the presence of erosive esophagitis and intestinal metaplasia on esophagoscopy was abstracted. The mean (±SD) age of the entire cohort (N = 20) was 63 (±7.7) years. 60% was female. The mean composite DeMeester pH score for persons with and without an EAR was 48.9 (±39.6) and 15.4 (±12.3), respectively (P = .033). The mean total % time of pH < 4 for persons with and without an EAR was 26.4 (±21.9) and 7.7 (±6.8), respectively (P = .034). The prevalence of erosive esophagitis among persons with and without an EAR was 70% and 10%, respectively (P = .019). There is a significant association between the presence of esophageal A-rings on esophagography and the severity of acid reflux on endoscopy and ambulatory pH testing. The data suggest that the presence of an esophageal A-ring may be either a compensatory mechanism to protect against gastroesophageal reflux and/or an inflammatory consequence of peptic esophagitis. 3b Laryngoscope, 130:951-954, 2020.


Enthesopathy and desmitis of the medial collateral ligament of the cubital joint in 4 horses.
4 horses with enthesopathy and desmitis of the medial collateral ligament of the cubital joint were examined. All 4 horses had a history of acute, severe, unilateral forelimb lameness and had signs of pain during manipulation of the affected upper forelimb; 2 also had swelling in the axillary region. There was no improvement in lameness after diagnostic local analgesia below the carpal region, and 1 of 4 horses had mild improvement after cubital joint analgesia. Radiography revealed enthesophyte formation on the radial tuberosity and linear mineralization of the medial collateral ligament in 2 horses and periosteal reaction on the humeral condyle in all 4 horses. One horse had mild osteoarthritis of the cubital joint, and 3 had osteophytosis of the cranial aspect of the radius. Although all horses were initially examined because of an acute onset of lameness, all had chronic abnormalities visible on imaging. Ultrasonography revealed an irregular boney contour and enthesopathy at the insertion of the short medial collateral ligament to the radial tuberosity and desmitis of the short medial collateral ligament. Two horses had radiographic evidence of similar but less severe lesions of the contralateral cubital joint. All horses received phenylbutazone and rest. All horses were free of lameness after a median of 3 months (range, 2 to 4 months) and returned to previous use after a median of 6 months (range, 3 to 8 months). The results of the present report suggested that performance horses with enthesopathy and desmitis of the medial collateral ligament of the cubital joint may have a good prognosis for return to previous use following appropriate treatment.


The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.
Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained ∼25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation.


The genetics of common diseases: the implications of population variability.
The results of recent work on the inheritance of susceptibility to malaria suggest that, over what may have been a relatively short evolutionary period, a remarkably diverse series of gene families have been modified in response to the selective drive of this infectious disease. The phenotypic consequences are not confined to the erythrocyte, they also involve the immune system, cytokines and many other systems. It seems likely that the mechanisms of genetic susceptibility to current environmental agents will reflect at least a similar degree of complexity and, if the selective pressures have been present for longer periods of our evolutionary history, may be even more diverse. These issues are discussed in the light of current efforts to identify some of the major genes involved in variation in susceptibility to the common non-infectious diseases of the developed world.


Discrepancies in aortic growth explain aortic arch gradients during exercise.
This study was conducted to evaluate the incidence and etiology of hypertension and aortic arch gradients during exercise in patients who have apparent good coarctation repair assessed at rest. The reported incidence of recurrent aortic arch obstruction (rest gradient > 20 mm Hg) after previous successful surgical repair varies from 0% to 60% and usually is associated with recurrent stenosis at the site of surgical repair. Maximal treadmill exercise with Doppler echocardiographic gradient estimation was performed in 28 patients with a good coarctation repair at rest (normal blood pressure and arch gradient < 20 mm Hg) who had isolated coarctation repair a mean of 7.8 years previously. Eight (29%) developed systolic hypertension for age and a mean Doppler gradient of 45 +/- 13 mm Hg. At cardiac catheterization, the rest peak to peak systolic gradient (6 +/- 6 to 28 +/- 7 mm Hg, p < 0.001), peak systolic instantaneous gradient (16 +/- 11 to 48 +/- 9 mm Hg, p < 0.01) and cardiac index (3.5 +/- 0.7 to 5.9 +/- 1.1 liters/m per m2, p < 0.001) all increased during isoproterenol infusion. Angiographic systolic aortic arch measurements proximal to the innominate artery, left common carotid artery, left subclavian artery and the narrowest dimension at the coarctation repair site demonstrated hypoplasia at the left common carotid artery (11.8 +/- 1.7 vs. 16.7 +/- 2.9 mm/m2, p < 0.01) and left subclavian artery (11.6 +/- 1.7 vs. 15.4 +/- 3.1 mm/m2, p < 0.05) compared with findings in 10 patients with normal aortograms. Transverse aortic arch ratios were also smaller in the eight patients with abnormal findings. Preoperative angiographic ratios were not predictive of late postoperative findings. Exercise testing detects hypertension and arch gradients in patients with a good coarctation repair as assessed at rest. The hypertension and arch "obstruction" appear to be related to discrepancies in the growth of the transverse aortic arch proximal to the repair site, rather than a "recoarctation" of the aorta.


Wall shear rate distribution in an abdominal aortic bifurcation model: effects of vessel compliance and phase angle between pressure and flow waveforms.
The goal of this study was to determine how vessel compliance (wall motion) and the phase angle between pressure and flow waves (impedance phase angle) affect the wall shear rate distribution in an atherogenic bifurcation geometry under sinusoidal flow conditions. Both rigid and elastic models replicating the human abdominal aortic bifurcation were fabricated and the wall shear rate distribution in the median plane of the bifurcation was determined using the photochronic flow visualization method. In the elastic model, three phase angle conditions were simulated (+12, -17, -61 deg), and the results compared with those obtained in a similar rigid model. The study indicates a very low (magnitude close to zero) and oscillatory wall shear rate zone within 1.5 cm distal to the curvature site on the outer (lateral) wall. In this low shear rate zone, unsteadiness (pulsatility) of the flow greatly reduces the mean (time-averaged) wall shear rate level. Vessel wall motion reduces the wall shear rate amplitude (time-varying component) up to 46 percent depending on the location and phase angle in the model. The mean wall shear rate is less influenced by the wall motion, but is reduced significantly in the low shear region (within 1.5 cm distal to the curvature site on the outer wall), thus rendering the wall shear rate waveform more oscillatory and making the site appear more atherogenic. The effect of the phase angle is most noteworthy on the inner wall close to the flow divider tip where the mean and amplitude of wall shear rate are 31 and 23 percent lower, respectively, at the phase angle of -17 deg than at -61 deg. However, the characteristics of the wall shear rate distribution in the low shear rate zone on the outer wall that are believed to influence localization of atherosclerotic disease, such as the mean wall shear rate level, oscillation in the wall shear rate waveform, and the length of the low and oscillatory wall shear rate zone, are similar for the three phase angles considered. The study also showed a large spatial variation of the phase angle between the wall shear stress waveform and the circumferential stress waveform (hoop stress due to radial artery expansion in response to pressure variations) near the bifurcation (up to 70 deg). The two stresses became more out of phase in the low mean shear rate zone on the outer wall (wall shear stress wave leading hoop stress wave as much as 125 deg at the pressure-flow phase angle of -61 deg) and were significantly influenced by the impedance phase angle.


Toward epigenetic and gene regulation models of specific language impairment: looking for links among growth, genes, and impairments.
Children with specific language impairment (SLI) are thought to have an inherited form of language impairment that spares other developmental domains. SLI shows strong heritability and recent linkage and association studies have replicated results for candidate genes. Regulatory regions of the genes may be involved. Behavioral growth models of language development of children with SLI reveal that the onset of language is delayed, and the growth trajectories of children with SLI parallel those of younger children without SLI. The rate of language acquisition decelerates in the pre-adolescent period, resulting in immature language levels for the children with SLI that persist into adolescence and beyond. Recent genetic and epigenetic discoveries and models relevant to language impairment are reviewed. T cell regulation of onset, acceleration, and deceleration signaling are described as potential conceptual parallels to the growth timing elements of language acquisition and impairment. A growth signaling disruption (GSD) hypothesis is proposed for SLI, which posits that faulty timing mechanisms at the cellular level, intrinsic to neurocortical functioning essential for language onset and growth regulation, are at the core of the growth outcomes of SLI. The GSD highlights the need to document and account for growth patterns over childhood and suggests needed directions for future investigation.


White matter alterations in the brains of patients with active, remitted, and cured cushing syndrome: a DTI study.
Cushing syndrome appears after chronic exposure to elevated glucocorticoid levels. Cortisol excess may alter white matter microstructure. Our purpose was to study WM changes in patients with Cushing syndrome compared with controls by using DTI and the influence of hypercortisolism. Thirty-five patients with Cushing syndrome and 35 healthy controls, matched for age, education, and sex, were analyzed through DTI (tract-based spatial statistics) for fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity (general linear model, family-wise error, and threshold-free cluster enhancement corrections, P < .05). Furthermore, the influence of hypercortisolism on WM DTI changes was studied by comparing 4 subgroups: 8 patients with Cushing syndrome with active hypercortisolism, 7 with Cushing syndrome with medication-remitted cortisol, 20 surgically cured, and 35 controls. Cardiovascular risk factors were used as covariates. In addition, correlations were analyzed among DTI values, concomitant 24-hour urinary free cortisol levels, and disease duration. There were widespread alterations (reduced fractional anisotropy, and increased mean diffusivity, axial diffusivity, and radial diffusivity values; P < .05) in patients with Cushing syndrome compared with controls, independent of the cardiovascular risk factors present. Both active and cured Cushing syndrome subgroups showed similar changes compared with controls. Patients with medically remitted Cushing syndrome also had reduced fractional anisotropy and increased mean diffusivity and radial diffusivity values, compared with controls. No correlations were found between DTI maps and 24-hour urinary free cortisol levels or with disease duration. Diffuse WM alterations in patients with Cushing syndrome suggest underlying loss of WM integrity and demyelination. Once present, they seem to be independent of concomitant hypercortisolism, persisting after remission/cure.


Inhibition of cytokine signaling in human retinal endothelial cells through modification of caveolae/lipid rafts by docosahexaenoic acid.
Docosahexaenoic acid (DHA(22:6,n3)) is the principal n3 polyunsaturated fatty acid (PUFA) in the retina. The authors previously demonstrated that DHA(22:6,n3) inhibited cytokine-induced adhesion molecule expression in primary human retinal vascular endothelial (hRVE) cells, the target tissue affected by diabetic retinopathy. Despite the importance of vascular inflammation in diabetic retinopathy, the mechanisms underlying anti-inflammatory effects of DHA(22:6,n3) in vascular endothelial cells are not understood. In this study the authors address the hypothesis that DHA(22:6,n3) acts through modifying lipid composition of caveolae/lipid rafts, thereby changing the outcome of important signaling events in these specialized plasma membrane microdomains. hRVE cells were cultured in the presence or absence of DHA(22:6,n3). Isolated caveolae/lipid raft-enriched detergent-resistant membrane domains were prepared using sucrose gradient ultracentrifugation. Fatty acid composition and cholesterol content of caveolae/lipid rafts before and after treatment were measured by HPLC. The expression of Src family kinases was assayed by Western blotting and immunohistochemistry. Disruption of the caveolae/lipid raft structure with a cholesterol-depleting agent, methyl-cyclodextrin (MCD), diminished cytokine-induced signaling in hRVE cells. Growth of hRVE cells in media enriched in DHA(22:6,n3) resulted in significant incorporation of DHA(22:6,n3) into the major phospholipids of caveolae/lipid rafts, causing an increase in the unsaturation index in the membrane microdomain. DHA(22:6,n3) enrichment in the caveolae/raft was accompanied by a 70% depletion of cholesterol from caveolae/lipid rafts and displacement of the SFK, Fyn, and c-Yes from caveolae/lipid rafts. Adding water-soluble cholesterol to DHA(22:6,n3)-treated cells replenished cholesterol in caveolae/lipid rafts and reversed the effect of DHA(22:6,n3) on cytokine-induced signaling. Incorporation of DHA(22:6,n3) into fatty acyl chains of phospholipids in caveolae/lipid rafts, followed by cholesterol depletion and displacement of important signaling molecules, provides a potential mechanism for anti-inflammatory effect of DHA(22:6,n3) in hRVE cells.


Bacterial and fungal communities in a degraded ombrotrophic peatland undergoing natural and managed re-vegetation.
The UK hosts 15-19% of global upland ombrotrophic (rain fed) peatlands that are estimated to store 3.2 billion tonnes of carbon and represent a critical upland habitat with regard to biodiversity and ecosystem services provision. Net production is dependent on an imbalance between growth of peat-forming Sphagnum mosses and microbial decomposition by microorganisms that are limited by cold, acidic, and anaerobic conditions. In the Southern Pennines, land-use change, drainage, and over 200 years of anthropogenic N and heavy metal deposition have contributed to severe peatland degradation manifested as a loss of vegetation leaving bare peat susceptible to erosion and deep gullying. A restoration programme designed to regain peat hydrology, stability and functionality has involved re-vegetation through nurse grass, dwarf shrub and Sphagnum re-introduction. Our aim was to characterise bacterial and fungal communities, via high-throughput rRNA gene sequencing, in the surface acrotelm/mesotelm of degraded bare peat, long-term stable vegetated peat, and natural and managed restorations. Compared to long-term vegetated areas the bare peat microbiome had significantly higher levels of oligotrophic marker phyla (Acidobacteria, Verrucomicrobia, TM6) and lower Bacteroidetes and Actinobacteria, together with much higher ligninolytic Basidiomycota. Fewer distinct microbial sequences and significantly fewer cultivable microbes were detected in bare peat compared to other areas. Microbial community structure was linked to restoration activity and correlated with soil edaphic variables (e.g. moisture and heavy metals). Although rapid community changes were evident following restoration activity, restored bare peat did not approach a similar microbial community structure to non-eroded areas even after 25 years, which may be related to the stabilisation of historic deposited heavy metals pollution in long-term stable areas. These primary findings are discussed in relation to bare peat oligotrophy, re-vegetation recalcitrance, rhizosphere-microbe-soil interactions, C, N and P cycling, trajectory of restoration, and ecosystem service implications for peatland restoration.


A cross-sectional survey of 3035 patients with fibromyalgia: subgroups of patients with typical comorbidities and sensory symptom profiles.
Patients with FM are heterogeneous. They present with a variety of pain qualities, sensory abnormalities and additional comorbidities. The aim was to identify clinically distinguishable subgroups of patients. This investigation uses epidemiological and clinical data of 3035 FM patients from a cross-sectional survey (painDETECT) to (i) describe characteristic epidemiological data and comorbidities and (ii) detect subgroups of patients with typical patterns of sensory symptoms and comorbidities. Clinically relevant sensory abnormalities (strongly, very strongly present) included pressure pain (58%), prickling (33%), burning (30%) and thermal hypersensitivity (24%). Pain attacks were complained by 40% of patients. Moderate to severe comorbid depression occurred in 66% of patients. Only approximately 30% of the patients had optimal sleep. A hierarchical cluster analysis using descriptors of sensory abnormalities as well as the extent of comorbidities revealed five distinct subgroups of patients showing a characteristic clinical profile. Four subgroups of patients suffer from severe sensory disturbances in various combinations but lack pronounced comorbidities. In one subgroup, however, severe comorbidities dominate the clinical picture. Differences in pathophysiological mechanisms of pain generation can be attributed to each subgroup. The results of this study indicate that FM patients can be classified on the basis of their sensory symptoms and comorbidities by the use of a patient-reported questionnaire. Subgrouping of patients with FM may be used for future research and to tailor optimal treatment strategies for the appropriate patient.


Cloning and expression of the large-conductance Ca(2+)-activated K+ channel from colonic smooth muscle.
We have cloned cDNAs encoding the alpha- and beta-subunits of a large-conductance Ca(2+)-activated K+ channel (BK channel) from canine colonic smooth muscle (cslo-alpha and cslo-beta). Nucleotide sequence homology of cslo-alpha with mslo and dslo suggests that it is the canine homologue of these genes. The carboxy-terminal end of the protein is the most diverse between species, and we have also found alternative exons in cslo-alpha in this region. We have identified a unique splice site in the carboxy-terminal region of cslo-alpha, which we term site 5. Northern analysis demonstrates expression of both alpha- and beta-subunits in all canine vascular and visceral smooth muscles tested. Expression of alpha-1 alone and alpha + beta-subunit cRNA in Xenopus oocytes results in a Ca(2+)- and voltage-dependent conductance. The activity of alpha/beta-channels, measured as either changes in the voltage of half-maximal activation (V0.5) in open probability (NP0) or in the normalized conductance (G/Cmax), was more sensitive to [Ca2+]free than channels composed of the alpha-subunit alone. Neither alpha- nor alpha/beta-channels expressed in membrane patches of Xenopus oocytes were found to be regulated by protein kinase G.


Clinicians' perceptions of the benefits of aquatic therapy for young children with autism: a preliminary study.
This purpose of this study was to identify clinicians' perceptions of the benefits of aquatic therapy for young children with autism. Eighteen aquatic occupational therapists treating young children with autism responded to a survey soliciting their opinions on changes in skill performance resulting from aquatic therapy. A majority of clinicians reported a substantial increase in swim skills, attention,muscle strength, balance, tolerating touch, initiating/maintaining eye contact, and water safety. The impairments, activity limitations, and participation restrictions seen in children with autism can be wide-ranging and outcomes can be difficult to operationally define and measure. In this preliminary study, clinicians identified the areas they perceived as improving as a result of aquatic therapy. This information could help narrow the field of likely outcomes as a first step toward studies of the effectiveness of aquatic therapy for children with autism.


Predicting combined effects of land use and climate change on river and stream salinity.
Agricultural, industrial and urban development have all contributed to increased salinity in streams and rivers, but the likely effects of future development and climate change are unknown. I developed two empirical models to estimate how these combined effects might affect salinity by the end of this century (measured as electrical conductivity, EC). The first model predicts natural background from static (e.g. geology and soils) and dynamic (i.e. climate and vegetation) environmental factors and explained 78% of the variation in EC. I then compared the estimated background EC with current measurements at 2001 sites chosen probabilistically from all conterminous USA streams. EC was more than 50% greater at 34% of these sites. The second model predicts deviation of EC from background as a function of human land use and environmental factors and explained 60% of the variation in alteration from background. I then predicted the effects of climate and land use change on EC at the end of the century by replacing dynamic variables with published projections of future conditions based on the A2 emissions scenario. By the end of the century, the median EC is predicted to increase from 0.319 mS cm-1 to 0.524 mS cm-1 with over 50% of streams having greater than 50% increases in EC and 35% more than doubling their EC. Most of the change is related to increases in human land use, with climate change accounting for only 12% of the increase. In extreme cases, increased salinity may make water unsuitable for human use, but widespread moderate increases are likely a greater threat to stream ecosystems owing to the elimination of low EC habitats.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.


Surgical myocardial revascularization in the 1990s.
Substantial changes in the practice of cardiology ultimately produce a change in the types of patients who become candidates for surgery. This has been especially true for patients with coronary artery disease. The primary goals of coronary artery bypass graft (CABG) surgery are to relieve symptoms, prolong survival, and improve the quality of life. Because of recent improvements in pharmacologic therapy and medical interventions, the criteria used to select patients for CABG surgery has changed secondary to the clinical characteristics of the patient population.


Parental smoking and adolescent smoking initiation: an intergenerational perspective on tobacco control.
Adolescence is an important period of risk for the development of lifelong smoking behaviors. Compelling, although inconsistent, evidence suggests a relationship between parental smoking and the risk of smoking initiation during adolescence. This study investigates unresolved issues concerning the strength and nature of the association between parent smoking and offspring smoking initiation. We enrolled 564 adolescents aged 12 to 17, along with 1 of their parents, into the New England Family Study between 2001 and 2004. Lifetime smoking histories were obtained from parents and their adolescent offspring. Discrete-time survival analysis was used to investigate the influence of parental smoking histories on the risk of adolescent smoking initiation. Parental smoking was associated with a significantly higher risk of smoking initiation in adolescent offspring. In addition, the likelihood of offspring smoking initiation increased with the number of smoking parents and the duration of exposure to parental smoking, suggesting a dose-response relationship between parental smoking and offspring smoking. Offspring of parents who had quit smoking were no more likely to smoke than offspring of parents who had never smoked. The effects of parental smoking on offspring initiation differed by sex (with a stronger effect of fathers' smoking on boys than girls), developmental period (with a stronger effect of parental smoking before the adolescent was age 13 than afterward), and residence of parents (with effects of fathers' smoking being dependent on living in the same household as the adolescent). Parental smoking was also associated with stronger negative reactions to adolescents' first cigarette, a potential marker of the risk of progression to higher levels of use. Parental smoking is an important source of vulnerability to smoking initiation among adolescents, and parental smoking cessation might attenuate this vulnerability.


A quantitative evaluation of periprosthetic bone-remodeling after cementless total hip arthroplasty.
Dual-energy x-ray absorptiometry analysis was used to determine the periprosthetic bone-mineral content of ten femora that had been obtained at the autopsies of five elderly patients who had had an AML (anatomic medullary locking) prosthesis in situ for seventeen to eighty-four months. Clinical radiographs showed resorptive remodeling changes characteristic of femora containing this implant. Before the absorptiometry was performed, an identical prosthesis had been inserted into the contralateral, normal femur of each cadaver. The mean difference in the periprosthetic bone-mineral content between the remodeled femora and the femora in which the prosthesis had been implanted post mortem ranged from 7 to 52 per cent, with the bone-mineral content always less in the remodeled femora. The greatest mean decrease in bone-mineral content (45 per cent) occurred adjacent to the proximal one-third of the remodeled femora. The percentage decrease in periprosthetic bone-mineral content in the remodeled femora had an inverse linear relationship with the corresponding bone-mineral content of the contralateral control femora. Preoperative analysis of bone density may therefore be useful for prediction of the extent of resorptive bone-remodeling after total hip replacement.


Randomized trial of telephone outreach to improve medication adherence and metabolic control in adults with diabetes.
Medication nonadherence is a major obstacle to better control of glucose, blood pressure (BP), and LDL cholesterol in adults with diabetes. Inexpensive effective strategies to increase medication adherence are needed. In a pragmatic randomized trial, we randomly assigned 2,378 adults with diabetes mellitus who had recently been prescribed a new class of medication for treating elevated levels of glycated hemoglobin (A1C) ≥8% (64 mmol/mol), BP ≥140/90 mmHg, or LDL cholesterol ≥100 mg/dL, to receive 1) one scripted telephone call from a diabetes educator or clinical pharmacist to identify and address nonadherence to the new medication or 2) usual care. Hierarchical linear and logistic regression models were used to assess the impact on 1) the first medication fill within 60 days of the prescription; 2) two or more medication fills within 180 days of the prescription; and 3) clinically significant improvement in levels of A1C, BP, or LDL cholesterol. Of the 2,378 subjects, 89.3% in the intervention group and 87.4% in the usual-care group had sufficient data to analyze study outcomes. In intent-to-treat analyses, intervention was not associated with significant improvement in primary adherence, medication persistence, or intermediate outcomes of care. Results were similar across subgroups of patients defined by age, sex, race/ethnicity, and study site, and when limiting the analysis to those who completed the intended intervention. This low-intensity intervention did not significantly improve medication adherence or control of glucose, BP, or LDL cholesterol. Wide use of this strategy does not appear to be warranted; alternative approaches to identify and improve medication adherence and persistence are needed.


Centrally acting oximes in reactivation of tabun-phosphoramidated AChE.
Organophosphates (OP) inhibit acetylcholinesterase (AChE, EC 22.214.171.124), both in peripheral tissues and central nervous system (CNS), causing adverse and sometimes fatal effects due to the accumulation of neurotransmitter acetylcholine (ACh). The currently used therapy, focusing on the reactivation of inhibited AChE, is limited to peripheral tissues because commonly used quaternary pyridinium oxime reactivators do not cross the blood brain barrier (BBB) at therapeutically relevant levels. A directed library of thirty uncharged oximes that contain tertiary amine or imidazole protonable functional groups that should cross the BBB as unionized species was tested as tabun-hAChE conjugate reactivators along with three reference oximes: DAM (diacetylmonoxime), MINA (monoisonitrosoacetone), and 2-PAM. The oxime RS150D [N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide] was highlighted as the most promising reactivator of the tabun-hAChE conjugate. We also observed that oximes RS194B [N-(2-(azepan-1-yl)ethyl)-2-(hydroxyimino)acetamide] and RS41A [2-(hydroxyimino)-N-(2-(pyrrolidin-1-yl)ethyl)acetamide], which emerged as lead uncharged reactivators of phosphylated hAChE with other OPs (sarin, cyclosarin and VX), exhibited only moderate reactivation potency for tabun inhibited hAChE. This implies that geometry of oxime access to the phosphorus atom conjugated to the active serine is an important criterion for efficient reactivation, along with the chemical nature of the conjugated moiety: phosphorate, phosphonate, or phosphoramidate. Moreover, modification of the active center through mutagenesis enhances the rates of reactivation. The phosphoramidated-hAChE choline-binding site mutant Y337A showed three-times enhanced reactivation capacity with non-triazole imidazole containing aldoximes (RS113B, RS113A and RS115A) and acetamide derivative (RS194B) than with 2PAM.


Androgen prevents hypogonadal bone loss via inhibition of resorption mediated by mature osteoblasts/osteocytes.
Androgen receptor (AR) is expressed throughout the osteoblast lineage. Two different AR transgenic families (AR2.3-tg and AR3.6-tg mice) demonstrating overlapping and distinct expression profiles were employed to assess the effects of enhanced androgen sensitivity to ameliorate hypogonadal loss. Two different paradigms of steroid replacement following orchidectomy (ORX) were used as either preventative or therapeutic therapy. ORX was performed in male wild-type (WT), AR2.3-tg and AR3.6-tg mice at 5 months with immediate DHT replacement (prevention, higher turnover) or at 3 months with DHT treatment delayed for 2 months (therapeutic, lower turnover), both with treatment for the last 6 weeks. Dual energy X-ray absorptiometry (DXA), micro-computed tomography (μCT), and histomorphometry were performed. In the prevention model, ORX significantly reduced BMD and BMC in all genotypes compared to sham and DHT was effective at prevention of osteopenia. In the therapeutic model, all genotypes became osteopenic compared to sham, but after a prolonged hypogonadal period, delayed DHT treatment provided little benefit. μCT analysis of mid-shaft total bone in all genotypes generally showed reductions after ORX. Delayed DHT was ineffective at restoring bone volume in any genotype whereas immediate treatment prevented loss only in AR transgenic mice. Cortical thickness also decreased with ORX but immediate DHT treatment was effective to increase thickness only in WT mice, likely due to expansion of marrow volume in both AR-tg lines. In metabolically highly active cancellous bone, ORX resulted in lower bone volume/tissue volume (BV/TV) in all genotypes, consistent among 3 sites measured. Again with delayed treatment, there was little effect of DHT to restore BV/TV, but when administered at the time of ORX, DHT completely prevented the decrease in cancellous bone in all genotypes. Improvement in cancellous bone architecture was seen with immediate DHT replacement that was enhanced in AR transgenic lines compared to WT. In contrast, there were only modest changes in all genotypes using the delayed treatment paradigm. With ORX in both paradigms, trabecular number was decreased while spacing increased. Thus, androgen therapy is effective for the prevention of endosteal and cancellous osteopenia primarily through its anti-resorptive properties, but shows little anabolic action as a therapeutic strategy to restore bone. Given the similarity in response to androgen treatment in both AR transgenic lines, overlapping expression profiles suggest that the target cells mediating androgen action in vivo are mature osteoblast/osteocytes. Combined, these results demonstrate that in the adult mouse, androgen treatment can reduce bone resorption but has little overall anabolic activity.


The effect of condyle fossa relationships on head posture.
Although it is commonly accepted that there is an interrelationship between the temporomandibular joint (TMJ) and head posture, few, if any, previous studies have quantified this effect. The purpose of this study is to quantify the effect of a change in the condyle fossa relationship of symptomatic temporomandibular joints on head posture. Charts of 51 patients (N=10 men and N=41 women) with symptomatic TMJ pathology were reviewed. The condyle fossa relationships were measured pre- and posttreatment using sagittal corrected hypocycloidal tomography. The amount of slant between the shoulder and external auditory meatus (EAM) was measured in pre- and posttreatment photographs as an indicator of forward head posture; less slant indicates better posture. Subjects ranged in age from 13-74 years (mean=43.1) and had been treated for an average of 5 months. Comparisons with pre-treatment measures showed that after treatment, the amount of retrodiskal space was significantly increased by an average of 1.67 mm on the left side (t=-10.11, p<0.0001) and 1.92 mm on the right (t=-9.62, p<0.0001). Comparisons also showed that after treatment, the amount of slant between the shoulder and EAM decreased by 4.43 inches on average which was also significant (t=13.08, p<0.0001). Improvement in the condyle fossa relationship was related to decreased forward head posture. This suggests that optimizing mandibular condyle position should be considered in the management of forward head posture (adaptive posture).


The severity of dental caries in adults aged 35 to 44 years residing in the metropolitan area of a large city in Brazil: a cross-sectional study.
In recent decades, studies in the field of public health have increasingly focused on social determinants that affect the health-illness process. The epidemiological perspective considers oral health to be a reflection of socioeconomic and environmental aspects, and it is particularly influenced by the social context. The aim of the present study was to assess the association between the severity of dental caries among adults aged 35 to 44 years and characteristics on the different levels at which the determinants of caries operate (individual, social structure and social context). A home-based, cross-sectional field study was carried out involving a sample of 1,150 adults (35 to 44 years of age) residing in metropolitan Belo Horizonte, Brazil. The DMFT (decayed, missing, filled tooth) index (≥14) was used to determine the severity of dental caries. Bivariate and multivariate analyses were carried out using the Poisson regression model with the level of significance set at 5% (p < 0.05) and 95% confidence intervals. The majority of the participants (68.5%) had high caries severity. The rate of high-severity caries in the group between 40 and 44 years of age was 1.15-fold (CI: 1.04-1.26) greater than that among those aged 35 to 39 years. A greater prevalence of high caries severity was found among those who frequently visited the dentist (PR = 1.18; CI: 1.07-1.30), those with a lower income (PR = 1.11; CI: 1.01-1.23), those who reported that their neighborhood did not come together in the previous year to petition political leaders for benefits (PR = 1.16; CI: 1.05-1.28) and those who are unable to make decisions (without empowerment) (PR = 1.12; CI: 1.01-1.24). The present study revealed high dental caries severity in adults, which was associated with individual characteristics, health-related behavior and social structure and contextual variables. These findings underscore the importance of considering social determinants involved in the health-illness process when carrying out epidemiological studies on dental caries.


Endovascular treatment of true renal artery aneurysms: a single center experience.
We aimed to report a single center's experience on endovascular treatment of true renal artery aneurysms (TRAAs), including treatment techniques and outcomes. This retrospective study was designed to evaluate the treatment and follow-up of TRAAs treated by a variety of endovascular interventional techniques over a period of 6 years. Six patients with nine TRAAs were identified; seven of the TRAAs were treated using different combinations of coil embolization and flow diverter stents. The clinical findings, aneurysm characteristics, endovascular methods and treatment outcomes were reported. Seven TRAAs of six patients were treated, with a median aneurysm size of 20 mm. Three TRAAs were treated with primary sac occlusion (one with primary coil embolization, one with balloon and stent assisted coil and glue embolization, and one with amplatzer vascular occlusion device and coil embolization). The remaining four TRAAs of three patients were treated with flow diverter stents (Cardiatis, Silk, Pipeline, and Surpass). Immediate clinical success was achieved in patients treated with primary sac embolization (95% CI, 29.2%-100%). Among patients treated with flow diverter stents, one patient required an additional flow diverter at 6-month follow-up. The occlusion time in flow diverters ranged from 1 month to 12 months (median, 3.5 months) taking the repeat procedure into account. In patients treated with flow diverters, the clinical success rate was 100% (95% CI, 29.2%-100%) at one-year follow-up. Long-term follow-up ranged from 3 to 52 months. One intraprocedural complication was encountered with a flow diverter during deployment, which required additional stenting and tirofiban infusion. No other major complication was seen. Endovascular treatment is an effective and safe method offering high success rates and low morbidity in the treatment of TRAAs and may supplant surgery as the primary therapy. Current experience in the use of flow diverter stents in TRAAs is limited to individual case reports with one brand of flow diverter device. Our small numbered series of four TRAAs shows our experience regarding endovascular treatment with different flow diverter brands.


Preoperative PET and the reduction of unnecessary surgery among newly diagnosed lung cancer patients in a community setting.
The goals of this study were to examine the real-world effectiveness of PET in avoiding unnecessary surgery for newly diagnosed patients with non-small cell lung cancer. A cohort of 2,977 veterans with non-small cell lung cancer between 1997 and 2009 were assessed for use of PET during staging and treatment planning. The subgroup of 976 patients who underwent resection was assessed for several outcomes, including pathologic evidence of mediastinal lymph node involvement, distant metastasis, and 12-mo mortality. We anticipated that PET may have been performed selectively on the basis of unobserved characteristics (e.g., providers ordered PET when they suspected disseminated disease). Therefore, we conducted an instrumental variable analysis, in addition to conventional multivariate logistic regression, to reduce the influence of this potential bias. This type of analysis attempts to identify an additional variable that is related to receipt of treatment but not causally associated with the outcome of interest, similar to randomized assignment. The instrument here was calendar time. This analysis can be informative when patients do not receive the treatment that the instrument suggests they "should" have received. Overall, 30.3% of patients who went to surgery were found to have evidence of metastasis uncovered during the procedure or within 12 mo, indicating that nearly one third of patients underwent surgery unnecessarily. The use of preoperative PET increased substantially over the study period, from 9% to 91%. In conventional multivariate analyses, PET use was not associated with a decrease in unnecessary surgery (odds ratio, 0.87; 95% confidence interval, 0.66-1.16; P = 0.351). However, a reduction in unnecessary surgery (odds ratio, 0.53; 95% confidence interval, 0.34-0.82; P = 0.004) was identified in the instrumental variable analyses, which attempted to account for potentially unobserved confounding. PET has now become routine in preoperative staging and treatment planning in the community and appears to be beneficial in avoiding unnecessary surgery. Evaluating the effectiveness of PET appears to be influenced by potentially unmeasured adverse selection of patients, especially when PET first began to be disseminated in the community.


Early Childhood General Anesthesia and Neurodevelopmental Outcomes in the Avon Longitudinal Study of Parents and Children Birth Cohort.
Most common anesthetic agents have been implicated in causing neurodegeneration in the developing animal brain, leading to warnings regarding their use in children. The hypothesis of this study was that exposure to general anesthesia and surgery before 4 yr would associate with adverse neurodevelopmental outcomes at age 7 to 16 yr. This cohort study comprised 13,433 children enrolled in the Avon Longitudinal Study of Parents and Children, a prospective, population-based birth cohort born between 1991 and 1993 in southwest England. Children were grouped by none, single, or multiple exposures to general anesthesia and surgery by 4 yr. Motor, cognitive, linguistic, educational, social, and behavioral developmental outcomes were evaluated at 7 to 16 yr using school examination results, validated parent/teacher questionnaires, or clinic assessments. Continuous outcomes were z-scored. P-value thresholds were corrected using false discovery rate procedures. This study compared 46 neurodevelopmental outcomes in 13,433 children: 8.3% (1,110) exposed singly and 1.6% (212) exposed multiply to general anesthesia and surgery. Of these, the following reached predefined levels of statistical significance (corrected P < 0.00652): dynamic balance scores were 0.3 SD (95% CI, 0.1, 0.5; P < 0.001) lower in multiply exposed children; manual dexterity performance was 0.1 SD (95% CI, 0.0, 0.2; P = 0.006) lower in singly and 0.3 SD (95% CI, 0.1, 0.4; P < 0.001) lower in multiply exposed children; and social communication scores were 0.1 SD (95% CI, 0.0, 0.2; P = 0.001) and 0.4 SD (95% CI, 0.3, 0.5; P < 0.001) lower in singly and multiply exposed children, respectively. General anesthesia and surgery were not associated with impairments in the remaining neurodevelopmental measures including: general cognitive ability; attention; working memory; reading, spelling, verbal comprehension and expression; behavioral difficulties; or national English, mathematics, and science assessments (all ≤0.1 SD; corrected P ≥ 0.00652). Early childhood general anesthesia and surgery were not associated with a global picture of clinically and statistically significant neurodegenerative effects, providing reassurance about the neurotoxic potential of general anesthesia. Exposure to anesthesia and surgery was associated with significantly lower motor and social linguistic performance.


Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats.
6-hydroxy dopamine (6-OHDA) is a neurotoxin which on intranigral administration produces severe nigrostriatal damage with motor and cognitive deficit in animals. Curcumin (CMN) in combination with bioenhancer piperine (PP) in 6-hydroxydopamine-induced Parkinsonian rats was used to investigate the antioxidant, neuromodulatory and neuroprotective mechanisms. Hemi-Parkinson's rat model was developed with intranigral infusion of 6-OHDA (8 μg/2 μl, once, unilaterally), treatment with CMN (25 and 50 mg/kg) and combination of PP (2.5 mg/kg) with CMN (25 mg/kg) was given daily for 21 days starting from the 7th day after 6-OHDA infusion. The behavioral (locomotor, grip strength, and narrow beam walk) parameters were studied on weekly basis. On 22nd day, isolated brain preparations were subjected to biochemical (lipid peroxidation, glutathione, and nitrite), neuroinflammatory (IL-1β, IL-6, and TNF- α), and neurochemical (DA, NE, 5- HT, GABA, Glutamate, DOPAC, HVA, and 5-HIAA) analysis. Oral administration of CMN had significantly prevented behavioral, neuroinflammatory, and neurochemical changes and preserved the antioxidant potential of the nigrostriatum in rats treated with 6-OHDA. In the present study, PP and CMN had afforded a better neuroprotective effect compared to alone treatment on behavior, biochemical, neuroinflammatory, and neurochemical parameters in rats.


Implementation of an Advanced Nursing Directive for Children With Right Lower Quadrant Pain: Identifying Those Requiring Further Investigation and Improving Flow Metrics.
Advanced nursing directives (ANDs) empower nursing staff to provide advanced levels of care before physician assessment. The objectives of this study were (1) to determine whether an AND for right lower quadrant (RLQ) pain could identify children who required any further investigation to diagnose appendicitis and (2) to determine whether children meeting AND criteria had better emergency department (ED) flow metrics compared with those who did not meet the criteria. Health records of children aged 3 to 17 years presenting to the ED with abdominal pain who were managed using the departmental AND for RLQ pain were reviewed. Primary outcomes included (1) the proportion of patients requiring further investigation to diagnose appendicitis and (2) the time interval from triage to blood draw. Secondary outcomes included additional ED flow metrics, perforation rate, and negative appendectomy rate. An AND was completed for 210 children. Those who met the AND criteria were more likely to undergo further investigation to rule out appendicitis than those who did not meet the criteria (92/137 [67.2%] vs 32/73 [43.8%]; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.40-4.90). Time to blood draw was significantly lower for those children meeting the AND criteria (74 vs 162 minutes, P < 0.001) as was time to hospital admission (271 vs 395 minutes, P = 0.008) and appendectomy (498 vs 602 minutes, P = 0.015). The negative appendectomy rate was 8.6% (5/58) for children meeting the AND criteria and 9.1% (2/22) for those not meeting the criteria (OR, 0.94; 95% CI, 0.14-10.67); the perforation rate was 29.3% (17/58) and 4.5% (1/22), respectively (OR, 8.17; 95% CI, 1.17-380.86). Children presenting to the ED with RLQ pain who meet the AND criteria are more likely to require further investigation to rule out appendicitis and have better department flow metrics than those who do not meet the criteria. Our results provide further evidence of the utility of ANDs in the ED.


Protein-level fluctuation correlation at the microcolony level and its application to the Vibrio harveyi quorum-sensing circuit.
Gene expression is stochastic, and noise that arises from the stochastic nature of biochemical reactions propagates through active regulatory links. Thus, correlations in gene-expression noise can provide information about regulatory links. We present what to our knowledge is a new approach to measure and interpret such correlated fluctuations at the level of single microcolonies, which derive from single cells. We demonstrated this approach mathematically using stochastic modeling, and applied it to experimental time-lapse fluorescence microscopy data. Specifically, we investigated the relationships among LuxO, LuxR, and the small regulatory RNA qrr4 in the model quorum-sensing bacterium Vibrio harveyi. Our results show that LuxR positively regulates the qrr4 promoter. Under our conditions, we find that qrr regulation weakly depends on total LuxO levels and that LuxO autorepression is saturated. We also find evidence that the fluctuations in LuxO levels are dominated by intrinsic noise. We furthermore propose LuxO and LuxR interact at all autoinducer levels via an unknown mechanism. Of importance, our new method of evaluating correlations at the microcolony level is unaffected by partition noise at cell division. Moreover, the method is first-order accurate and requires less effort for data analysis than single-cell-based approaches. This new correlation approach can be applied to other systems to aid analysis of gene regulatory circuits.


Inhibition of lipoxygenase by sesamol corroborates its potential anti-inflammatory activity.
Reactive oxygen species, the byproducts of oxygenases reaction, when in excess, promote degenerative diseases like cardiovascular, cancer and arthritis. Sesame lignans- sesamin, sesamolin and the phenolic degradation product of sesamolin, sesamol, are empirically known for their health promoting properties like antioxidant, antimutagenic, antiaging and antiinflammatory activities. In the current study, the effect of sesamol on the inflammatory oxygenase - lipoxygenase (LOX) was investigated. Enzyme kinetics and spectroscopic techniques were used to understand the inhibition mechanism. Sesamol was a potent inhibitor of soy LOX-1. It inhibited soy LOX-1 in a dose dependent manner with IC50 value of 51.84μM and Ki of 4.9μM. Binding studies using circular dichroism and corroborated by surface plasmon resonance, revealed that sesamol does not bind or change the conformation of LOX. Further, sesamol prevented the conversion of inactive LOX (Fe2+) to active LOX (Fe3+) by arresting the oxidation state of iron and prolonging the lag phase by virtue of its ability to scavenge hydroperoxides. Understanding the mechanism of action of such molecules will help in their application and promotion as nutraceuticals.


Characterization, prophylaxis, and treatment of infectious complications in craniomaxillofacial and upper extremity allotransplantation: a multicenter perspective.
Vascularized composite allotransplants consist of heterogeneous tissues from different germ layers, which include skin, muscle, bone, fat, nerves, and lymph nodes. The antigenic diversity of these tissues, particularly of the highly immunogenic skin component, necessitates potent immunosuppressive regimens similar to that of some solid organ transplants. Indeed, the lifelong, high-dose, multidrug immunosuppressive protocols expose vascularized composite allotransplant recipients to considerable risk of infectious, metabolic, and neoplastic sequelae. In this article, the authors review the infectious risk to patients after vascularized composite allotransplantation, with special attention to the somewhat limited experience with the prophylaxis and treatment of infections after this innovative reconstructive surgery. A review of the literature was undertaken to elucidate the characterization, prophylaxis, and treatment of all documented infectious complications. Infections in face and hand vascularized composite allotransplants follow a course similar to that of solid organ transplants. Several differences exist, including the unique flora of craniomaxillofacial transplants, the increased risk of donor-derived infections, and the alteration of the risk-to-benefit ratio for cytomegalovirus infections. The patient with a face or limb transplant has many of the same infectious risks as a lung transplant recipient, which include bacterial, viral, and fungal infections. Because of the anatomy, mucosal exposure, and differing donor flora, however, the face or limb transplant is susceptible to invasive diseases from a variety of microbes.


Inflammatory Characteristics of Stenotic Aortic Valves: A Comparison between Rheumatic and Nonrheumatic Aortic Stenosis.
Background. Although our comprehension of nonrheumatic aortic stenosis (NRAS) has increased substantially during the last decade, less is known about the histopathology of rheumatic aortic stenosis (RAS). The aim of this study was to investigate rheumatic aortic stenosis by means of analyses previously used in nonrheumatic stenosis. Material and Methods. Valve specimens were obtained from 39 patients referred to hospital due to significant aortic stenosis. According to established macroscopic criteria the valves were divided into two groups consisting of 29 NRAS and 10 RAS valves. Mononuclear inflammatory cells and apolipoproteins were investigated using immunohistochemical analyses. Results. The localisation of calcification differed in tricuspid nonrheumatic valves when compared to bicuspid nonrheumatic and rheumatic valves. The RAS valves revealed a lower degree of T lymphocyte infiltration compared with the NRAS valves. Infiltration of macrophages was seen in all valves and there were no differences regarding deposition of apolipoprotein. Conclusion. Rheumatic and nonrheumatic aortic stenotic valves show a similar and significant chronic inflammation. The similarities regarding the localisation of calcification indicate that the valve anomaly/morphology can influence the pathogenesis of aortic stenosis. Finally, our findings highlight the question of a postinflammatory valvular disease of other causes than rheumatic fever.


Biosynthesis of the respiratory formate dehydrogenases from Escherichia coli: characterization of the FdhE protein.
Escherichia coli can perform two modes of formate metabolism. Under respiratory conditions, two periplasmically-located formate dehydrogenase isoenzymes couple formate oxidation to the generation of a transmembrane electrochemical gradient; and under fermentative conditions a third cytoplasmic isoenzyme is involved in the disproportionation of formate to CO(2) and H(2). The respiratory formate dehydrogenases are redox enzymes that comprise three subunits: a molybdenum cofactor- and FeS cluster-containing catalytic subunit; an electron-transferring ferredoxin; and a membrane-integral cytochrome b. The catalytic subunit and its ferredoxin partner are targeted to the periplasm as a complex by the twin-arginine transport (Tat) pathway. Biosynthesis of these enzymes is under control of an accessory protein termed FdhE. In this study, it is shown that E. coli FdhE interacts with the catalytic subunits of the respiratory formate dehydrogenases. Purification of recombinant FdhE demonstrates the protein is an iron-binding rubredoxin that can adopt monomeric and homodimeric forms. Bacterial two-hybrid analysis suggests the homodimer form of FdhE is stabilized by anaerobiosis. Site-directed mutagenesis shows that conserved cysteine motifs are essential for the physiological activity of the FdhE protein and are also involved in iron ligation.


Genome and chromosome wide association studies for growth traits in Simmental and Simbrah cattle.
The objective of this study was to perform genome (genome wide association studies [GWAS]) and chromosome (CWAS) wide association analyses to identify single nucleotide polymorphisms (SNPs) associated with growth traits in registered Simmental and Simbrah cattle. The phenotypes were deregressed BLUP EBVs for birth weight, weaning weight direct, weaning weight maternal, and yearling weight. The genotyping was performed with the GGP Bovine 150k chip. After the quality control analysis, 105,129 autosomal SNP from 967 animals (473 Simmental and 494 Simbrah) were used to carry out genotype association tests. The two association analyses were performed per breed and using combined information of the two breeds. The SNP associated with growth traits were mapped to their corresponding genes at 100 kb on either side. A difference in magnitude of posterior probabilities was found across breeds between genome and chromosome wide association analyses. A total of 110, 143, and 302 SNP were associated with GWAS and CWAS for growth traits in the Simmental-, Simbrah-and joint -data analyses, respectively. It stands out from the enrichment analysis of the pathways for RNA polymerase (POLR2G, POLR3E) and GABAergic synapse (GABRR1, GABRR3) for Simmental cattle and p53 signaling pathway (BID, SERPINB5) for Simbrah cattle. Only 6,265% of the markers associated with growth traits were found using CWAS and GWAS. The associated markers using the CWAS analysis, which were not associated using the GWAS, represents information that due to the model and priors was not associated with the traits.


1-stage versus 2-stage lateral maxillary sinus lift procedures: 4-month post-loading results of a multicenter randomised controlled trial.
To compare the efficacy of 1-stage versus 2-stage lateral maxillary sinus lift procedures. Sixty partially edentulous patients requiring 1 to 3 implants and having 1 to 3 mm of residual bone height and at least 5 mm of bone width below the maxillary sinus, as measured on CT scans, were randomised into two equal groups to receive either a 1-stage lateral window sinus lift with simultaneous implant placement or a 2-stage procedure with implant placement delayed by 4 months using a bone substitute in 3 different centres. Implants were submerged for 4 months and loaded with reinforced provisional prostheses, which were replaced, after 4 months, by definitive prostheses. Outcome measures were augmentation procedure failures, prosthesis failures, implant failures, complications and marginal peri-implant bone loss assessed by a blinded outcome assessor. Patients were followed up to 4 months after loading. Only data of implants placed in 1 to 3 mm of bone height were reported. Two patients dropped out from the 1-stage group and none from the 2-stage group. No sinus lift procedure failed in the 1-stage group but 1 failed in the 2-stage group, the difference was not statistically significant (P = 1.00). Two prostheses failed or could not be placed in the planned time in the 1-stage group and 1 in the 2-stage group, the difference was not statistically significant (P = 0.51). Three implants failed in 3 patients of the 1-stage group versus 1 implant in the 2-stage group, the difference was not statistically significant (P = 0.28). Two complications occurred in the 1-stage group and 1 in the 2-stage group, the difference was not statistically significant (P = 0.61). There were no statistically significant differences in bone loss between groups at loading (0.05 mm). Sites treated in 1 stage lost an average of 0.56 mm (SD: 0.36; 95% CI: -0.70 to -0.42; P < 0.001) of peri-implant bone and 2-stage sites approximately 0.61 mm (SD: 0.34; 95% CI: -0.74 to -0.48; P < 0.001). No statistically significant differences were observed between implants placed according to 1- or 2-stage sinus lift procedures. However, this study may suggest that in patients having a residual bone height between 1 and 3 mm below the maxillary sinus there might be a slightly higher risk for implant failures when performing a 1-stage lateral sinus lift procedure.


Nonrealistic behavior of mean-field spin glasses.
We study chaotic size dependence of the low-temperature correlations in the Sherrington-Kirkpatrick (SK) spin glass. We prove that as temperature scales to zero with volume, for any typical coupling realization, the correlations cycle through every spin configuration in every fixed observation window. This cannot happen in short-ranged models as there it would mean that every spin configuration is an infinite-volume ground state. Its occurrence in the SK model means that the commonly used "modified clustering" notion of states sheds little light on the replica symmetry breaking (RSB) solution of SK, and, conversely, the RSB solution sheds little light on the thermodynamic structure of Edwards-Anderson models.


SU-D-217A-06: Impact of Anterior-Posterior (AP) and Posterior-Anterior (PA) Scout Scans on the CT Radiation Dose in the Whole Body PET/CT Scan.
CT can contribute over 50% of radiation dose in the whole body (WB) PET/CT scan. Tube current modulation (TCM) is a standard technique for reducing CT radiation dose to the patient by changing the tube current with the patient size, and is controlled by a very low-dose scoutscan, which assumes the patient is positioned at the center of the CT gantry opening. However, most patients are not positioned at the center due to practicality or to avoid claustrophobic or to reduce time of radiation exposure from the patient to the technologist. We study the impact of the AP and PA scout scans to the patient radiation exposure from CT. Ina retrospective study of 200 patients, each received two WB PET/CT scans: one with AP, and the other one with PA. The helical CT with TCM and PET acquisitions were identical in both scans. Separation of the two scans was about 10 months in average. The scans were performed on four GE PET/CT scanners: three 16- and one 64-slice with the same TCM settings. The 200patients were selected for the same scan coverage and similar body weight (difference = 3 kg). The tube current in each slice and average exposure tothe patient were recorded and compared. The AP scout caused lower radiation dose on 94% of the patients. Both the tube current, and radiation exposure were reduced by 46±30 mA and 1.6±1.0 mGy, respectively. The effective radiation dose is reduced by 1.7±1.2 mSv. These results were statistically significant (p<0.00001). The AP scout caused significantly less radiation dose than the PA scout in the CT scan of the whole-body PET/CT scan. Care should be taken to select theorientation of the scout scan to achieve appropriate radiation exposure to the patient when TCM is applied.


Dietary intervention for people with mental illness in South Australia.
People with serious mental illness (SMI) have a 25-30 year lower life expectancy than the general population due largely to cardiovascular disease (CVD). Mediterranean diet can reduce CVD risk and repeat events by 30-70%. We conducted a pilot feasibility study (HELFIMED) with people who have SMI residing within a Community Rehabilitation Centre in South Australia, aimed at improving participants' diets according to Mediterranean diet principles. During a 3-month intervention, participants were provided with nutrition education, food hampers, and twice-weekly cooking workshops and guided shopping trips. This report presents the results of a mixed method evaluation of the programme using thorough in-depth interviews with participants and support staff (n = 20), contextualized by changes in dietary biomarkers and CVD risk factors. The framework thematic analysis revealed evidence of improvements in participants' knowledge of and intake of the key elements of a Mediterranean-style diet (fruit and vegetables, olive oil, fish, legumes), reduction in poor nutrition habits (soft drinks, energy drinks, take away meals) and development of independent living skills-culinary skills such as food preparation and cooking based on simple recipes, food shopping and budgeting, healthy meal planning and social interaction. These changes were supported by dietary biomarkers, and were associated with reduced CVD risk factors. A Mediterranean diet-based pilot study achieved positive change in dietary behaviours associated with CVD risk for participants with SMI. This supports a need to include dietary education and cooking skills into rehabilitation programmes for people with SMI.


Recombinant factor VIIa for the correction of coagulopathy before emergent craniotomy in blunt trauma patients.
Recombinant activated factor VII (rFVIIa) has been associated with decreased blood transfusion requirements in trauma patients. Clinical use has recently been extended to the treatment of coagulopathic patients with traumatic brain injury, and results have been encouraging. However, the cost and possible thromboembolic complications of rFVIIa have been considered barriers to its widespread use. We hypothesize that rFVIIa would provide an effective and cost efficient means of correcting coagulopathy in patients with traumatic brain injury undergoing emergent craniotomy. We performed a 2-year (2005-2006) retrospective study of adult blunt trauma patients with traumatic brain injury who presented coagulopathic (international normalized ratio [INR] >1.3) and required emergent craniotomy. We compared patients who did (rFVIIa group) and did not (no-rFVIIa group) receive rFVIIa to correct coagulopathy before craniotomy. There were 14 rFVIIa patients and 14 no-rFVIIa patients. The rFVIIa patients were older (59 years vs. 41 years, p = 0.04), but there was no difference in male gender (79% vs. 79%, p = 0.68), injury severity score (29 vs. 29, p = 1.0), or Glasgow Coma Scale score (10 vs. 7, p = 0.67). Although there was no difference in admission INR (2.6 vs. 1.9, p = 0.10), the rFVIIa group was more often taking preinjury coumadin (57% vs. 14%, p = 0.05). The rFVIIa group had a preoperative INR (1.2 +/- 0.4 vs. 1.4 +/- 0.2, p = 0.05), but there was no difference in the time from admission to craniotomy (135 minutes vs. 182 minutes, p = 0.51). The rFVIIa group received fewer units of packed red blood cells (PRBCs) and plasma during the perioperative period. In addition, the rVIIa group consumed fewer costs of PRBC ($756 per patient vs. $2,916 per patient, p < 0.001) and plasma ($369 per patient vs. $927 per patient, p = 0.001). The rFVIIa group still consumed fewer total costs of transfused blood products when cost of rFVIIa was included ($2,557 per patient vs. $4,110 per patient, p = 0.04). There were no thromboembolic complications in either group. rFVIIa provides a cost-efficient option to effectively correct coagulopathy in patients with traumatic brain injury undergoing emergent craniotomy. In addition, the use of rFVIIa is associated with decreased transfusion of PRBC and plasma and decreased transfusion-related hospital costs in this population.


Globally optimal cortical surface matching with exact landmark correspondence.
We present a method for establishing correspondences between human cortical surfaces that exactly matches the positions of given point landmarks, while attaining the global minimum of an objective function that quantifies how far the mapping deviates from conformality. On each surface, a conformal transformation is applied to the Euclidean distance metric, resulting in a hyperbolic metric with isolated cone point singularities at the landmarks. Equivalently, each surface is mapped to a hyperbolic orbifold: a pillow-like surface with each point landmark corresponding to a pillow corner. An initial surface-to-surface mapping exactly aligns the landmarks, and gradient descent is used to find the single, global minimum of the Dirichlet energy of the remainder of the mapping. Using a population of real MRI-based cortical surfaces with manually labeled sulcus endpoints as landmarks, we evaluate the approach by how much it distorts surfaces and by its biological plausibility: how well it aligns previously-unseen anatomical landmarks and by how well it promotes expected associations between cortical thickness and age. We show that, compared to a painstakingly-tuned approach that balances a tradeoff between minimizing landmark mismatch and Dirichlet energy, our method has similar biological plausibility, superior surface distortion, a better theoretical foundation, and fewer arbitrary parameters to tune. We also compare to conformal mapper in the spherical domain to show that sacrificing exact conformality of the mapping does not cause noticeable reductions in biological plausibility.