Carriage of potentially fish-pathogenic bacteria in Sparus aurata cultured in Mediterranean fish farms.
A bacteriological survey of gilthead sea bream Sparus aurata from different fish farms and culture systems on the Spanish Mediterranean coast was conducted. Three different studies were performed. Study A included hatchery-reared larvae; Study B, periodic examination of randomly sampled growing fish; and Study C, growing fish sampled only during mortality/morbidity events. In Studies B and C, sea cages, earth ponds and indoor tanks were surveyed, and in both cases diseased (showing clinical signs) and non-diseased fish were included. In Study A, a shift from Vibrio spp. (30 d after hatching) to oxidative species (60 d after hatching) was detected, and no mortality events were registered. The percentage of fish yielding bacterial growth were similar in Studies B and C, reaching 57.4 and 61.3%, respectively. A statistically significant relationship between the bacterial carriage and the type of facility was only found in Study B, showing that fish from sea cages had a higher bacterial occurrence than fish from other facilities. A statistically significant relationship between bacterial carriage and signs of disease was found, although the pattern differed in each study. Thus, in Study B only 36.2% of fish yielding abundant bacterial growth were diseased, versus 68.0% in Study C. In total, 25.0% of the fish examined were diseased. Bacterial species composition was similar in asymptomatic and diseased fish, except for a group of V. ichthyoenteri-like isolates that occurred almost exclusively in asymptomatic fish. Dominant bacterial species were V. harveyi and V. splendidus, followed by V. ichthyoenteri-like isolates, Photobacterium damselae ssp. damselae and V. fisheri. Non-fermenters were less frequent but, among them, unidentified halophilic Cytophaga-Flavobacterium isolates and Pseudoalteromonas haloplanktis were the most abundant. An association of individual species with disease was not clear, which suggests the involvement of mixed infections.


Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.
We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.


Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration.
Emery-Dreifuss muscular dystrophy (EDMD1) is caused by mutations in either the X-linked gene emerin (EMD) or the autosomal lamin A/C (LMNA) gene. Here, we describe the derivation of mice lacking emerin in an attempt to derive a mouse model for EDMD1. Although mice lacking emerin show no overt pathology, muscle regeneration in these mice revealed defects. A bioinformatic array analysis of regenerating Emd null muscle revealed abnormalities in cell-cycle parameters and delayed myogenic differentiation, which were associated with perturbations to transcriptional pathways regulated by the retinoblastoma (Rb1) and MyoD genes. Temporal activation of MyoD transcriptional targets was significantly delayed, whereas targets of the Rb1/E2F transcriptional repressor complex remained inappropriately active. The inappropriate modulation of Rb1/MyoD transcriptional targets was associated with up-regulation of Rb1, MyoD and their co-activators/repressors transcripts, suggesting a compensatory effort to overcome a molecular block to differentiation at the myoblast/myotube transition during regeneration. This compensation appeared to be effective for MyoD transcriptional targets, although was less effective for Rb1 targets. Analysis of Rb1 phosphorylation states showed prolonged hyper-phosphorylation at key developmental stages in Emd null myogenic cells, both in vivo and in vitro. We also analyzed the same pathways in Lmna null muscle, which shows extensive dystrophy. Surprisingly, Lmna null muscle did not show the same perturbations to Rb- and MyoD-dependent pathways. We did observe increased transcriptional expression of Lap2alpha and delayed expression of Rb1, which may regulate alternative transcriptional pathways in the Lmna null myoblasts. We suggest that the dominant LMNA mutations seen in many clinically disparate laminopathies may similarly alter Rb function, with regard to either the timing of exit from the cell cycle or terminal differentiation programs or both.


Plasma levels of polychlorinated biphenyls (PCB) and the risk of soft tissue sarcoma.
Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS. To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk. We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models. The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff's classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff's groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04). Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.


An exploration of the influence of diagonal dissociation and moderate changes in speed on locomotor parameters in trotting horses.
Background. Although the trot is described as a diagonal gait, contacts of the diagonal pairs of hooves are not usually perfectly synchronized. Although subtle, the timing dissociation between contacts of each diagonal pair could have consequences on gait dynamics and provide insight into the functional strategies employed. This study explores the mechanical effects of different diagonal dissociation patterns when speed was matched between individuals and how these effects link to moderate, natural changes in trotting speed. We anticipate that hind-first diagonal dissociation at contact increases with speed, diagonal dissociation at contact can reduce collision-based energy losses and predominant dissociation patterns will be evident within individuals. Methods. The study was performed in two parts: in the first 17 horses performed speed-matched trotting trials and in the second, five horses each performed 10 trotting trials that represented a range of individually preferred speeds. Standard motion capture provided kinematic data that were synchronized with ground reaction force (GRF) data from a series of force plates. The data were analyzed further to determine temporal, speed, GRF, postural, mass distribution, moment, and collision dynamics parameters. Results. Fore-first, synchronous, and hind-first dissociations were found in horses trotting at (3.3 m/s ± 10%). In these speed-matched trials, mean centre of pressure (COP) cranio-caudal location differed significantly between the three dissociation categories. The COP moved systematically and significantly (P = .001) from being more caudally located in hind-first dissociation (mean location = 0.41 ± 0.04) through synchronous (0.36 ± 0.02) to a more cranial location in fore-first dissociation (0.32 ± 0.02). Dissociation patterns were found to influence function, posture, and balance parameters. Over a moderate speed range, peak vertical forelimb GRF had a strong relationship with dissociation time (R = .594; P < .01) and speed (R = .789; P < .01), but peak vertical hindlimb GRF did not have a significant relationship with dissociation time (R = .085; P > 0.05) or speed (R = .223; P = .023). Discussion. The results indicate that at moderate speeds individual horses use dissociation patterns that allow them to maintain trunk pitch stability through management of the cranio-caudal location of the COP. During the hoof-ground collisions, reduced mechanical energy losses were found in hind-first dissociations compared to fully synchronous contacts. As speed increased, only forelimb vertical peak force increased so dissociations tended towards hind-first, which shifted the net COP caudally and balanced trunk pitching moments.


Selecting optical patterns with spatial phase modulation.
Optical pattern selection by use of spatial phase modulation is investigated experimentally in a photorefractive feedback system. A feedback mirror with spatially periodic phase modulation is used for selection of different spatial patterns. Local phase modulation is used to create patterns with coexisting spatial symmetries. The experimental results are consistent with numerical simulations based on a model with a cubicly nonlinear medium.


Accurate identification and quantification of commensal microbiota bound by host immunoglobulins.
Identifying which taxa are targeted by immunoglobulins can uncover important host-microbe interactions. Immunoglobulin binding of commensal taxa can be assayed by sorting bound bacteria from samples and using amplicon sequencing to determine their taxonomy, a technique most widely applied to study Immunoglobulin A (IgA-Seq). Previous experiments have scored taxon binding in IgA-Seq datasets by comparing abundances in the IgA bound and unbound sorted fractions. However, as these are relative abundances, such scores are influenced by the levels of the other taxa present and represent an abstract combination of these effects. Diversity in the practical approaches of prior studies also warrants benchmarking of the individual stages involved. Here, we provide a detailed description of the design strategy for an optimised IgA-Seq protocol. Combined with a novel scoring method for IgA-Seq datasets that accounts for the aforementioned effects, this platform enables accurate identification and quantification of commensal gut microbiota targeted by host immunoglobulins. Using germ-free and Rag1-/- mice as negative controls, and a strain-specific IgA antibody as a positive control, we determine optimal reagents and fluorescence-activated cell sorting (FACS) parameters for IgA-Seq. Using simulated IgA-Seq data, we show that existing IgA-Seq scoring methods are influenced by pre-sort relative abundances. This has consequences for the interpretation of case-control studies where there are inherent differences in microbiota composition between groups. We show that these effects can be addressed using a novel scoring approach based on posterior probabilities. Finally, we demonstrate the utility of both the IgA-Seq protocol and probability-based scores by examining both novel and published data from in vivo disease models. We provide a detailed IgA-Seq protocol to accurately isolate IgA-bound taxa from intestinal samples. Using simulated and experimental data, we demonstrate novel probability-based scores that adjust for the compositional nature of relative abundance data to accurately quantify taxon-level IgA binding. All scoring approaches are made available in the IgAScores R package. These methods should improve the generation and interpretation of IgA-Seq datasets and could be applied to study other immunoglobulins and sample types. Video abstract.


Identification and characterization of a fibroblast marker: FSP1.
We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen deposition and also in tubular epithelium adjacent to the inflammatory process. This pattern of anti-FSP1 staining during tissue fibrosis suggests, as a hypothesis, that fibroblasts in some cases arise, as needed, from the local conversion of epithelium. Consistent with this notion that FSP1 may be involved in the transition from epithelium to fibroblasts are experiments in which the in vitro overexpression of FSP1 cDNA in tubular epithelium is accompanied by conversion to a mesenchymal phenotype, as characterized by a more stellate and elongated fibroblast-like appearance, a reduction in cytokeratin, and new expression of vimentin. Similarly, tubular epithelium submerged in type I collagen gels exhibited the conversion to a fibroblast phenotype which includes de novo expression of FSP1 and vimentin. Use of the FSP1 marker, therefore, should further facilitate both the in vivo studies of fibrogenesis and the mapping of cell fate among fibroblasts.


Does Diagnosis Make a Difference? Estimating the Impact of an HIV Medication Adherence Intervention for Persons with Serious Mental Illness.
The heightened risk of persons with serious mental illness to contract and transmit human immunodeficiency virus (HIV) is a public health problem. Here we evaluate the interaction between psychiatric diagnosis and response to a community based-intervention targeted at treatment adherence in 236 HIV+ persons with co-occurring mental illness. To examine differential effectiveness of the intervention for categories of patient diagnosis, we reanalyzed the data after stratifying participants into two diagnostic groups: (1) participants with depressive disorders without psychosis and (2) participants with a psychotic or bipolar disorder. Outcomes included viral load and mental health quality of life (SF-12 Mental Health). We found that HIV+ persons with non-psychotic depressive disorders demonstrated a larger decrease in HIV viral load and more improvement in measures of mental health quality of life when compared to HIV+ persons with psychotic and bipolar disorders. We suggest that successful adherence interventions should be informed by psychiatric symptomatology. clinicaltrials.gov 29 identifier NCT00264823.


Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
We have found a novel activity in Tetrahymena cell free extracts that adds tandem TTGGGG repeats onto synthetic telomere primers. The single-stranded DNA oligonucleotides (TTGGGG)4 and TGTGTGGGTGTGTGGGTGTGTGGG, consisting of the Tetrahymena and yeast telomeric sequences respectively, each functioned as primers for elongation, while (CCCCAA)4 and two nontelomeric sequence DNA oligomers did not. Efficient synthesis of the TTGGGG repeats depended only on addition of micromolar concentrations of oligomer primer, dGTP, and dTTP to the extract. The activity was sensitive to heat and proteinase K treatment. The repeat addition was independent of both endogenous Tetrahymena DNA and the endogenous alpha-type DNA polymerase; and a greater elongation activity was present during macronuclear development, when a large number of telomeres are formed and replicated, than during vegetative cell growth. We propose that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.


The influence of electromagnetic fields generated by wireless connectivity systems on the occurrence of emotional disorders in women: A preliminary report.
The aim of the study was to assess the influence of electromagnetic fields (EMFs) generated by wireless connectivity systems on the occurrence of emotional disorders in women working in the health service and in trade. We also analyzed the relationship between physical activity and emotional state. The study was conducted on a sample of 200 women aged 25 to 35, in Lublin, Poland, in 2017. Shopping center staff spent more time using their mobile phones for conversations and online activities. Medical staff were exposed to stronger electromagnetic fields generated by stationary wireless phones than shopping center staff, they were less exposed to the effect of relay stations. The study showed that exposure to electromagnetic fields from GSM 900 and 1800 generated by base stations contributed to the occurrence of depressive disorders among medical personnel, while exposure to WLAN EMF had the opposite effect. Spending time on phone conversations decreased the feeling of depression and increased trait anxiety in medical staff. Spending free time on physical activity intensified depressive states in women working in trade. Further studies on the influence of low-frequency EMFs on the human nervous system are needed.


Novel software strategy for glaucoma diagnosis: asymmetry analysis of retinal thickness.
The benefits of high-speed, detailed retinal thickness measurement by spectral-domain optical coherence tomography in glaucoma diagnosis have not been fully realized. We have modified the software protocols for such measurement and applied it for diagnosis at different stages of glaucoma. Using the Spectralis SD-OCT (Heidelberg Engineering, Carlsbad, California), we have customized the retinal thickness protocol to acquire detailed retinal thickness measurements of the central 20° of the posterior pole. These custom maps are displayed in a compressed color scale that reveals small losses in retinal thickness. A novel asymmetry analysis protocol was created to highlight differences between the eyes and the 2 hemispheres within each eye. We present case examples illustrating the ability of this strategy to detect glaucomatous defects, showing the promise of the protocol in the diagnosis and management of glaucoma.


The illusion of invariant quantities in life histories.
Life-history theory attempts to provide evolutionary explanations for variations in the ways in which animal species live their lives. Recent analyses have suggested that the dimensionless ratios of several key life-history parameters are the same for different species, even across distant taxa. However, we show here that previous analyses may have given a false picture and created an illusion of invariants, which do not necessarily exist; essentially, this is because life-history variables have been regressed against themselves. The following question arises from our analysis: How do we identify an invariant?


Physical side-effects following breast reconstructive surgery impact physical activity and function.
To investigate the incidence and severity of physical side-effects experienced by women following breast reconstructive surgery and the effect of these side-effects on physical activity and function. Two hundred and thirty-one Australian women (55 years SD 6.5) who had previously had breast reconstruction surgery retrospectively self-reported the incidence and severity of eight physical side-effects and the perceived effect of these side effects on six physical functions, at three time points after their surgery. The frequency of the combined incidence/severity scores and their impact at the three time points were tabulated and compared using Chi-squared tests. A general linear regression was used to identify characteristics associated with moderate-very high (≥ 5/10) combined incidence/severity scores. At 6 months following surgery, approximately 50% of respondents reported moderate to very high incidence/severity scores for physical side-effects across multiple body regions, which were perceived to limit their physical function and activity levels. The highest incidence/severity scores were associated with the following: (i) pre-existing physical problems before surgery, (ii) post-operative complications (seroma, infection, necrosis), and (iii) autologous rather than implant-based reconstructions. A large percentage of women reported moderate to severe physical side-effects across multiple body regions following breast reconstructive surgery. These side-effects were perceived to negatively impact both physical function and activity. Early intervention, education and treatment are recommended to alleviate these issues and minimise their negative impact.


Regulation of ion transport by endothelins in rat colonic mucosa: effects of an ETA antagonist (FR139317) and an ETB agonist (IRL1620).
Rat colonic mucosa contains ETA and ETB receptors with Kd values for endothelin (ET)-1 of 32 and 11 pM and maximal binding capacities of 277 and 181 fmol/mg protein, respectively. In muscle-stripped rat colon without tonic nerve activity in Ussing chambers, the serosal addition of ET-1, ET-3 and IRL1620 inhibited amiloride-sensitive noncoupled Na+ entry and enhanced diphenylamine-2-carboxylate-sensitive Cl- secretion, producing a sustained decrease and a transient increase in the short-circuit current (Isc) and the transepithelial conductance, respectively. EC50 values of ET-1, ET-3 and IRL1620 and the maximal changes in Isc were 2.0, 10.2 and 10.9 nM and -12.7, -7.0 and -7.1 muA/cm2, respectively for the Na+ entry; these values were 50, 220 and 225 nM and +57.3, +47.3 and +21.3 muA/cm2, respectively, for the Cl- secretion. FR139317 (100 nM) inhibited ET-1-induced Na+ and Cl- movements, shifting the concentration-response curves to the right (EC50 = 25 nM and 1 microM, respectively), and inhibited ET-3 (> 100 nM)-induced Cl- movement, decreasing the maximal response to 35%, but it did not inhibit either ET-3-induced Na+ movement nor IRL1620-induced Na+ and Cl- movements. The removal of serosal Ca++ reduced 100 nM ET-1- and IRL1620-evoked changes in Isc by 50% and 70% for the Na+ entry and by 80% and 100% for the Cl- secretion, respectively. Indomethacin (1 microM) also reduced changes in Isc by 30% and 70% for the Cl- secretion but did not affect the Na+ entry. Our results show that ETA and ETB receptors regulate Na+ and Cl- transport by different mechanisms.


Reconfigurable quantum metamaterials.
By coupling controllable quantum systems into larger structures we introduce the concept of a quantum metamaterial. Conventional meta-materials represent one of the most important frontiers in optical design, with applications in diverse fields ranging from medicine to aerospace. Up until now however, metamaterials have themselves been classical structures and interact only with the classical properties of light. Here we describe a class of dynamic metamaterials, based on the quantum properties of coupled atom-cavity arrays, which are intrinsically lossless, reconfigurable, and operate fundamentally at the quantum level. We show how this new class of metamaterial could be used to create a reconfigurable quantum superlens possessing a negative index gradient for single photon imaging. With the inherent features of quantum superposition and entanglement of metamaterial properties, this new class of dynamic quantum metamaterial, opens a new vista for quantum science and technology.


Crimean-Congo hemorrhagic fever nosocomial infection in a immunosuppressed patient, Pakistan: case report and virological investigation.
Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Baluchistan province, Pakistan. Sporadic outbreaks of CCHF occur throughout the year especially in individuals in contact with infected livestock. Nosocomial transmission remains a risk due to difficulties in the diagnosis of CCHF and limited availability of facilities for the isolation of suspected patients. Rapid diagnosis of CCHF virus infection is required for early management of the disease and to prevent transmission. This study describes the case of a 43-year-old surgeon who contracted CCHF during a surgical procedure in Quetta, Baluchistan and who was transferred to a tertiary care facility at the Aga Khan University Hospital, Karachi within 1 week of contracting the infection. Diagnosis of CCHF was made using a rapid real-time reverse transcription polymerase chain reaction (RT-PCR) assay for CCHF viral RNA. The patient had chronic hepatitis B and hepatitis D infection for which he had previously received a liver transplant. He proceeded to develop classic hemorrhagic manifestations and succumbed to the infection 14 days post-onset of disease. There was no further nosocomial transmission of the CCHF during the hospital treatment of the surgeon. Early diagnosis of CCHF enables rapid engagement of appropriate isolation, barrier nursing and infection control measures thus preventing nosocomial transmission of the virus.


Insecticide-mediated up-regulation of cytochrome P450 genes in the red flour beetle (Tribolium castaneum).
Some cytochrome P450 (CYP) genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR) revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively), permethrin (2.00- and 2.03-fold) and lambda-cyhalothrin (1.73- and 1.81-fold), whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold) when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.


Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy.
Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein. SMN is a critical mediator of spliceosomal protein assembly, and complete loss or drastic reduction in protein leads to loss of cell viability. However, the reason for selective motor neuron degeneration when SMN is reduced to levels which are tolerated by all other cell types is not currently understood. Widespread splicing abnormalities have recently been reported at end-stage in a mouse model of SMA, leading to the proposition that disruption of efficient splicing is the primary mechanism of motor neuron death. However, it remains unclear whether splicing abnormalities are present during early stages of the disease, which would be a requirement for a direct role in disease pathogenesis. We performed exon-array analysis of RNA from SMN deficient mouse spinal cord at 3 time points, pre-symptomatic (P1), early symptomatic (P7), and late-symptomatic (P13). Compared to littermate control mice, SMA mice showed a time-dependent increase in the number of exons showing differential expression, with minimal differences between genotypes at P1 and P7, but substantial variation in late-symptomatic (P13) mice. Gene ontology analysis revealed differences in pathways associated with neuronal development as well as cellular injury. Validation of selected targets by RT-PCR confirmed the array findings and was in keeping with a shift between physiologically occurring mRNA isoforms. We conclude that the majority of splicing changes occur late in SMA and may represent a secondary effect of cell injury, though we cannot rule out significant early changes in a small number of transcripts crucial to motor neuron survival.


Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance.
Although human embryonic stem (ES) cells may one day provide a renewable source of tissues for cell replacement therapy (CRT), histoincompatibility remains a significant barrier to their clinical application. Current estimates suggest that surprisingly few cell lines may be required to facilitate rudimentary tissue matching. Nevertheless, the degree of disparity between donor and recipient that may prove acceptable, and the extent of matching that is therefore required, remain unknown. To address this issue using a mouse model of CRT, we have derived a panel of ES cell lines that differ from CBA/Ca recipients at defined genetic loci. Here, we show that even expression of minor histocompatibility (mH) antigens is sufficient to provoke acute rejection of tissues differentiated from ES cells. Nevertheless, despite their immunogenicity in vivo, transplantation tolerance may be readily established by using minimal host conditioning with nondepleting monoclonal antibodies specific for the T cell coreceptors, CD4 and CD8. This propensity for tolerance could be attributed to the paucity of professional antigen-presenting cells and the expression of transforming growth factor (TGF)-beta(2). Together, these factors contribute to a state of acquired immune privilege that favors the polarization of infiltrating T cells toward a regulatory phenotype. Although the natural privileged status of ES cell-derived tissues is, therefore, insufficient to overcome even mH barriers, our findings suggest it may be harnessed effectively for the induction of dominant tolerance with minimal therapeutic intervention.


Malone antegrade continence enema: Is cecal imbrication essential?
The Malone antegrade continence enema (MACE) procedure is effective in management of fecal incontinence and intractable constipation. Stomal incontinence and stenosis are the most common issues reported, and a recent large study of imbricated MACE procedures reports a surgical revision rate of 17%. The laparoscopic approach is now widely used and precludes imbrication. To date, few studies have reported revision rates in these patients who have undergone non-imbricated MACE creation. Our goal was to report the long-term outcomes of our non-imbricated patients focusing on complication rates and need for revision. Records of patients younger than 18 years of age who underwent non-imbricated MACE between January 2000 and March 2016 at our institution were reviewed. Patients with less than 2 years of follow-up or non-compliance with MACE usage were excluded from analysis. Patient age, ambulatory status, surgical technique, stomal site, and complications including stomal leakage, stomal stenosis, and need for revision were evaluated. Stomal leakage was classified based on our previously reported system. A total of 81 patients met inclusion criteria. Mean age at time of surgery was 8.4 years. Mean and median follow-up were 6.7 and 6.7 years, respectively. Overall revision rate, for stenosis or incontinence, was 16% with a mean time to any revision of 2.1 years (range 28 days to 7.8 years). Four patients required revision for stomal incontinence while others improved spontaneously without intervention. At the last follow-up, stomal leakage was grade 0 in 93.8% of patients, grade 2 in 2.4%, and grade 3a in 3.7% (summary Table). Stomal stenosis was noted in 11 patients, eight of whom required revision. Our study is limited by its retrospective nature with some component of recall bias. A single surgeon experience is also not representative of others' experiences. However, our results indicate that incontinence improves spontaneously in a majority of patients without need for revision in this non-imbricated cohort. Our series shows a similar long-term revision rate in line with that reported in the literature. While imbrication is still recommended during open surgery when the anatomy is suitable, equitable success without imbrication supports the laparoscopic approach and a more liberal approach during open surgery if the anatomy does not permit imbrication.


Mammography: influence of departmental practice and women's characteristics on patient satisfaction: comparison of six departments in Norway.
To investigate how departmental practice and women's characteristics are related to low patient satisfaction with mammography. Survey of patients by means of self administered questionnaires before and after mammography. 488 women (89% of those invited), aged 23-86 years, at six departments. Low level of satisfaction measured on psychometric scales of physical pain, psychological distress, staff punctuality and technical skills, information provided, and physical surroundings. Satisfaction varied by department on the scales for pain, punctuality, information, and surroundings. After adjustment for women's characteristics an attributable risk of negative outcome by department was identified on the scales for pain, distress, punctuality, information, and surroundings. Adjusted odds ratio (ORs) ranged from 0.3 (95% confidence interval (95% CI) 1.2 to 6.0) on the pain scale, to 6.0 (2.9 to 12.3) on the punctuality scale. After adjustment for confounding variables, higher risk of dissatisfaction was associated with age < 50, nervousness about mammography, expected pain, lack of knowledge about mammography, and distrust in mammography (adjusted OR (95% CI) ranged from 1.6 (1.0 to 2.7) to 3.7 (2.0 to 7.3)). Departmental practices differed for breast compression, information, punctuality, and facilities and were associated with a low level of satisfaction irrespective of patient characteristics. Women's lack of knowledge about mammography and distrust in the procedure were confirmed as risk factors for dissatisfaction. All these factors might be helped by training the staff, improving facilities, and informing the women.


Universal scaling of Lyapunov-exponent fluctuations in space-time chaos.
Finite-time Lyapunov exponents of generic chaotic dynamical systems fluctuate in time. These fluctuations are due to the different degree of stability across the accessible phase space. A recent numerical study of spatially extended systems has revealed that the diffusion coefficient D of the Lyapunov exponents (LEs) exhibits a nontrivial scaling behavior, D(L)~L(-γ), with the system size L. Here, we show that the wandering exponent γ can be expressed in terms of the roughening exponents associated with the corresponding "Lyapunov surface." Our theoretical predictions are supported by the numerical analysis of several spatially extended systems. In particular, we find that the wandering exponent of the first LE is universal: in view of the known relationship with the Kardar-Parisi-Zhang equation, γ can be expressed in terms of known critical exponents. Furthermore, our simulations reveal that the bulk of the spectrum exhibits a clearly different behavior and suggest that it belongs to a possibly unique universality class, which has, however, yet to be identified.


Histopathologic evaluation of adipose autografts in a rabbit ear model.
Injection of autologous adipose tissue removed via liposuction has been used clinically for facial contouring, the aging face, furrows, facial atrophy, acne scars, nasolabial folds, chin, and various other surgical defects. Survival rates for autografts of fat have been quoted anywhere from 30% to 80%. Our study uses a reproducible rabbit animal model for autotransplantation of adipose tissue and examines the histopathologic changes that occur to the graft over time. Autogenous subcutaneous fat was removed from a dorsal scapular donor site, treated to stimulate cannula damage as in liposuction, then reinjected at the base of the ear. Histologic examination of the grafts were made at 5, 10, 15, 20, 40, and 100 days after transplantation. Hematoxylin-eosin sections were graded on degree of fibrosis present (0 to 4+), viable fat (1 to 10), degree of inflammation (0 to 4+), and neovascularization (+ or -). Viability of fat decreased from 8.5 to 10 at 5 days to 2 viability at 40 days. Acute inflammation peaked at 10 days, followed by the chronic inflammatory response with macrophages and multinucleated giant cells scavenging the dying fat graft. Neovascularization began at 5 days, peaked at 10 days, and remained constant thereafter only at the edge of the graft. Microcysts appeared at 15 days and increased in number in proportion to the decrease in viable fat. In summary, the temporal histologic events are progressive fibrosis; decreased amount of viable fat; inflammation beginning with a neutrophilic response, later a macrophage and giant cell response; and neovascularization at the periphery of the graft insufficient to maintain graft viability.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence of and risk factors for colonization by methicillin-resistant Staphylococcus aureus among adults in community settings in Taiwan.
In order to determine the prevalence of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) colonization among adults in community settings in Taiwan and identify its risk factors, we conducted the present study. For a 3-month period, we enrolled all adults who attended mandatory health examinations at three medical centers and signed the informed consent. Nasal swabs were taken for the isolation of S. aureus. For each MRSA isolate, we performed multilocus sequence typing, identification of the staphylococcal cassette chromosome mec, tests for the presence of the Panton-Valentine leukocidin gene, and tests for drug susceptibilities. Risk factors for MRSA colonization were determined. The results indicated that the MRSA colonization rate among adults in the community settings in Taiwan was 3.8% (119/3,098). Most MRSA isolates belonged to sequence type 59 (84.0%). Independent risk factors for MRSA colonization included the presence of household members less than 7 years old (P < 0.0001) and the use of antibiotics within the past year (P = 0.0031). Smoking appeared to be protective against MRSA colonization (P < 0.0001).


Negative self-evaluation and the genesis of internal threat: beyond a continuum of suicidal thought and behaviour.
Death by suicide is often preceded by attempted suicide, suicidal ideation and non-suicidal self-injury. These extreme thoughts and behaviours have been considered in terms of a continuum of suicidality. Little known research, however, has considered a suicide continuum that extends beyond these extreme thoughts and behaviours and incorporates a much wider array of phenomena that may vary in severity and may constitute a broader negative self-evaluation (NSE) continuum. Harvesting key indicators of NSE from a British epidemiological survey (N = 8580), the current study used exploratory factor analysis, confirmatory factor analysis and factor mixture modelling to (i) identify the dimensional structure of NSE in the general population and (ii) profile the distribution of the resultant NSE dimensions. Multinomial logistic regression was then used to differentiate between classes using an array of risk variables, psychopathology outcome variables and a suicide attempt indicator. A 4-factor model that reflected graded levels of NSE was identified; (F1) Low self-worth & subordination (F2) depression, (F3) suicidal thoughts, (F4) self-harm (SH). Seven classes suggested a clear pattern of NSE severity. Classes characterised by higher levels across the dimensions exhibited greater risk and poorer outcomes. The greatest risk for suicide attempt was associated with a class characterised by engagement in SH behaviour. Low self-worth, subordination and depression, while representative of distinct groups in the population are also highly prevalent in those who entertain suicidal thoughts and engage in SH behaviour. The findings promote further investigation into the genesis and evolution of suicidality and internal threat.


Precision of distances and ordering of microsatellite markers in consensus linkage maps of chromosomes 1, 3 and 4 from two reciprocal chicken populations using bootstrap sampling.
Some factors complicate comparisons between linkage maps from different studies. This problem can be resolved if measures of precision, such as confidence intervals and frequency distributions, are associated with markers. We examined the precision of distances and ordering of microsatellite markers in the consensus linkage maps of chromosomes 1, 3 and 4 from two F(2) reciprocal Brazilian chicken populations, using bootstrap sampling. Single and consensus maps were constructed. The consensus map was compared with the International Consensus Linkage Map and with the whole genome sequence. Some loci showed segregation distortion and missing data, but this did not affect the analyses negatively. Several inversions and position shifts were detected, based on 95% confidence intervals and frequency distributions of loci. Some discrepancies in distances between loci and in ordering were due to chance, whereas others could be attributed to other effects, including reciprocal crosses, sampling error of the founder animals from the two populations, F(2) population structure, number of and distance between microsatellite markers, number of informative meioses, loci segregation patterns, and sex. In the Brazilian consensus GGA1, locus LEI1038 was in a position closer to the true genome sequence than in the International Consensus Map, whereas for GGA3 and GGA4, no such differences were found. Extending these analyses to the remaining chromosomes should facilitate comparisons and the integration of several available genetic maps, allowing meta-analyses for map construction and quantitative trait loci (QTL) mapping. The precision of the estimates of QTL positions and their effects would be increased with such information.


A resource for the assessment of lung nodule size estimation methods: database of thoracic CT scans of an anthropomorphic phantom.
A number of interrelated factors can affect the precision and accuracy of lung nodule size estimation. To quantify the effect of these factors, we have been conducting phantom CT studies using an anthropomorphic thoracic phantom containing a vasculature insert to which synthetic nodules were inserted or attached. Ten repeat scans were acquired on different multi-detector scanners, using several sets of acquisition and reconstruction protocols and various nodule characteristics (size, shape, density, location). This study design enables both bias and variance analysis for the nodule size estimation task. The resulting database is in the process of becoming publicly available as a resource to facilitate the assessment of lung nodule size estimation methodologies and to enable comparisons between different methods regarding measurement error. This resource complements public databases of clinical data and will contribute towards the development of procedures that will maximize the utility of CT imaging for lung cancer screening and tumor therapy evaluation.


Incidence of Acute, Progressive, and Delayed Proximal Junctional Kyphosis Over an 8-Year Period in Adult Spinal Deformity Patients.
Proximal junctional kyphosis (PJK) is a common radiographic complication of adult spinal deformity (ASD) corrective surgery. Although previous literature has reported a 5 to 61% incidence of PJK, these studies are limited by small sample sizes and short-term follow-up. To assess the incidence of PJK utilizing a high-powered ASD database. Retrospective review of a prospective multicenter ASD database. Operative ASD patients > 18 yr old from 2009 to 2017 were included. PJK was defined as ≥ 10° for the sagittal Cobb angle between the inferior upper instrumented vertebra (UIV) endplate and the superior endplate of the UIV + 2. Chi-square analysis and post hoc testing assessed annual and overall incidence of acute (6-wk follow-up [f/u]), progressive (increase in degree of PJK from 6 wk to 1 yr), and delayed (1-yr, 2-yr, and 3-yr f/u) PJK development. A total of 1005 patients were included (age: 59.3; 73.5% F; body mass index: 27.99). Overall PJK incidence was 69.4%. Overall incidence of acute PJK was 48.0%. Annual incidence of acute PJK has decreased from 53.7% in 2012 to 31.6% in 2017 (P = .038). Overall incidence of progressive PJK was 35.0%, with stable rates observed from 2009 to 2016 (P = .297). Overall incidence of 1-yr-delayed PJK was 9.3%. Annual incidence of 1-yr-delayed PJK has decreased from 9.2% in 2009 to 3.2% in 2016 (P < .001). Overall incidence of 2-yr-delayed PJK development was 4.3%. Annual incidence of 2-yr-delayed PJK has decreased from 7.3% in 2009 to 0.9% in 2015 (P < .05). Overall incidence of 3-yr-delayed PJK was 1.8%, with stable rates observed from 2009 to 2014 (P = .594). Although progressive PJK has remained a challenge for physicians over time, significantly lower incidences of acute and delayed PJK in recent years may indicate improving operative decision-making and management strategies.


Pancreas transplantation from donors after circulatory death from the United Kingdom.
This study reports the comparative short-term results of pancreas transplantation from donors after circulatory death (DCD) (Maastricht III & IV), and pancreases from brainstem deceased donors (DBD). Between January 2006 and December 2010, 1009 pancreas transplants were performed in the United Kingdom, with 134 grafts from DCD and 875 from DBD. DCD grafts had no premortem pharmacological interventions performed. One-year pancreas and patient survival was similar between DCD and DBD, with pancreas graft survival significantly better in the DCD cohort if performed as an SPK. Early graft loss due to thrombosis (8% vs. 4%) was mainly responsible for early graft loss in the DCD cohort. These results from donors with broader acceptance criteria in age, body mass index, premortem interventions, etc. suggest that DCD pancreas grafts may have a larger application potential than previously recognized.


Changes in cerebral blood flow during olfactory stimulation in patients with multiple chemical sensitivity: a multi-channel near-infrared spectroscopic study.
Multiple chemical sensitivity (MCS) is characterized by somatic distress upon exposure to odors. Patients with MCS process odors differently from controls. This odor-processing may be associated with activation in the prefrontal area connecting to the anterior cingulate cortex, which has been suggested as an area of odorant-related activation in MCS patients. In this study, activation was defined as a significant increase in regional cerebral blood flow (rCBF) because of odorant stimulation. Using the well-designed card-type olfactory test kit, changes in rCBF in the prefrontal cortex (PFC) were investigated after olfactory stimulation with several different odorants. Near-infrared spectroscopic (NIRS) imaging was performed in 12 MCS patients and 11 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included subjective assessment of physical and psychological status and the perception of irritating and hedonic odors. Significant changes in rCBF were observed in the PFC of MCS patients on both the right and left sides, as distinct from the center of the PFC, compared with controls. MCS patients adequately distinguished the non-odorant in 10 odor repetitions during the early stage of the olfactory stimulation test, but not in the late stage. In comparison to controls, autonomic perception and negative affectivity were poorer in MCS patients. These results suggest that prefrontal information processing associated with odor-processing neuronal circuits and memory and cognition processes from past experience of chemical exposure play significant roles in the pathology of this disorder.


The knowledge levels of health personnel in Turkey regarding forensic evidence.
It is important that health personnel have extensive and adequate knowledge and practice regarding forensic evidence. This article describes the knowledge and practices of health personnel, who work in emergency rooms and health centers, regarding forensic evidence. The health personnel in a city in Central Anatolia, Turkey, constitute the population of this descriptive study and 233 personnel constitute its sample. It was determined that 31.3% stated that the practices of forensic evidence collection are inadequate. It was determined that average knowledge scores of health personnel with respect to forensic evidence are 23.5 ± 7.28 of 40. It was found that there was a statistically significant difference between knowledge scores on the subject of forensic with respect to duty (p = 0.005), level of education (p = 0.005), and institution of health personnel (p = 0.015). It was determined that the scores of the health personnel, who work in emergency services and health centers, on the subject of forensic evidence, are not at a desirable level.


Acetaminophen: a central analgesic drug that involves a spinal tropisetron-sensitive, non-5-HT(3) receptor-mediated effect.
The reversal of the antinociceptive effect of systemically administered acetaminophen (paracetamol) by intrathecal administration of the potent 5-HT(3) receptor antagonist tropisetron has been reported in rats subjected to the paw pressure test, suggesting that acetaminophen action is mediated through spinal 5-HT(3) receptors. However, more recent data, showing differences between the pharmacological profiles of various 5-HT(3) receptor antagonists, led us to reconsider the involvement of spinal 5-HT(3) receptors. To address this question, two different approaches were used: 1) electrophysiological recordings to assess whether acetaminophen directly modulates 5-HT(3) receptor activity and 2) pharmacological investigations with various 5-HT(3) receptor antagonists and spinal 5-HT(3) receptors antisense oligodeoxynucleotides (AODNs) to determine how those treatments might affect the antinociceptive action of acetaminophen. Electrophysiological studies demonstrated that acetaminophen had no direct agonist or antagonist effects on 5-HT(3A) receptors. Unlike tropisetron, other 5-HT(3) receptor antagonists, such as ondansetron and granisetron, injected intrathecally were unable to reverse the antinociceptive effect of acetaminophen. Moreover, pretreatment with AODNs did not reverse the acetaminophen-induced antinociceptive effect, although it suppressed the antinociceptive effect of m-chlorophenylbiguanide, a specific agonist of 5-HT(3) receptors, and significantly reduced (30%) the expression of these receptors in the dorsal horn of the spinal cord. These results suggest that acetaminophen-induced antinociceptive action involves a spinal tropisetron-sensitive receptor that is not the 5-HT(3) receptor and that remains to be identified.


RETRACTED: Treatment of nonparaphilic hypersexuality in men with a long-acting analog of gonadotropin-releasing hormone.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Following the retraction of Dr. Safarinejad's work by other journals, The Journal of Sexual Medicine has undertaken an extensive re-review of all papers Dr. Safarinejad published with the journal. Following an intensive re-evaluation and close scrutiny of the manuscripts, our expert reviewers raised multiple concerning questions about the methodology, results, and statistical interpretation as presented in this article. Dr. Safarinejad was contacted to provide his original data and offer explanations to address the concerns expressed by the reviewers. Dr Safarinejad chose not to respond. Consequently, we can no longer verify the results or methods as presented and therefore retract the article.


Assessment of coronary artery stenosis by magnetic resonance imaging.
The findings of magnetic resonance and x-ray angiography were compared for assessment of coronary artery stenosis in this validation study. Magnetic resonance angiography of the coronary arteries has recently been described, but there has been no comparison with x-ray angiography of localisation or assessment of important characteristics of coronary stenosis. A breath hold, segmented k-space, 2D gradient echo imaging technique incorporating fat suppression was used in 39 patients (55 coronary stenoses) with known coronary artery disease. Overall, 47 stenoses (85%) were assessed by magnetic resonance (29 of 33 stenoses in the left anterior descending artery, one of one in the left main stem, 14 of 17 in the right coronary artery, and three of four in the left circumflex artery were detected). There was close agreement between magnetic resonance and x-ray angiography for the distance of the stenosis from the arterial origin (magnetic resonance mean (SD) 27 (16) mm versus x-ray angiography 27 (16) mm, P = NS, mean difference -0.2 mm). The distance to 39 stenoses (83%) agreed to within 5 mm, with increased scatter for more distal stenoses. The severity of magnetic resonance signal loss, assessed visually at the site of stenosis, varied significantly according to the percentage diameter stenosis (F = 30, P < 0.0001); stenosis severity with severe signal loss was 89 (7)%, with partial signal was 70 (16)%, and with irregular wall only 37 (11)%, with significant differences among the three groups (P < 0.001). A significant correlation was found between the proportional magnetic resonance signal loss at the stenosis and the percentage diameter stenosis severity (r = -0.67, P < 0.0001). The length of stenosis measured by magnetic resonance (6 (3) mm) was greater than by x-ray angiography (5 (2) mm, P < 0.006, mean difference +1.1 mm). Spearman's rank test showed that there was significant overestimation of stenosis length by magnetic resonance as stenosis severity increased (rs = 0.34, P < 0.02). Accurate localisation of coronary stenosis and a qualitative assessment of stenosis severity are possible by magnetic resonance, but stenosis length is overestimated as severity increases, probably because of disturbed patterns of flow with turbulence distal to severe stenoses. Reasonable results for the detection of coronary artery stenosis by magnetic resonance were achieved in this highly selected population, but further progress in imaging techniques is necessary before moving towards appreciable clinical application.


The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat.
To investigate the effects of Xanthigen (brown marine algae fucoxanthin + pomegranate seed oil (PSO)) on body weight, body fat, liver lipids, and blood biochemistry; and Xanthigen and its individual components on resting energy expenditure (REE) in obese, non-diabetic female volunteers with non-alcoholic fatty liver disease (NAFLD) and normal liver fat (NLF) content. Sixteen-week, double-blind, randomized, placebo-controlled study. Food record data, body composition, REE (only 41 volunteers with NAFLD) and blood sample analysis were assessed weekly for 16 weeks in 151 non-diabetic, obese premenopausal women with liver fat content above 11% (NAFLD) n = 113, and below 6.5% (NLF) n = 38. Xanthigen-600/2.4 mg (300 mg PSO + 300 mg brown seaweed extract containing 2.4 mg fucoxanthin) resulted in statistically significant reduction of body weight (5.5 +/- 1.4 kg NAFLD group and 4.9 +/- 1.2 kg NLF group, p < 0.05), waist circumference (NAFLD group only), body (3.5 +/- 1.9 kg NAFLD group, p < 0.001; 3.6 +/- 0.7 kg NLF group, p < 0.05) and liver fat content, liver enzymes (NAFLD group only), serum triglycerides and C-reactive protein. Weight loss and reduction in body and liver fat content occurred earlier in patients with NLF than in patients with NAFLD. Fucoxanthin (> 2.4 mg) and Xanthigen-400/1.6 mg (200 mg PSO + 200 mg brown seaweed extract containing 1.6 mg fucoxanthin) significantly increased REE in NAFLD subjects compared to placebo. Xanthigen promoted weight loss, reduced body and liver fat content, and improved liver function tests in obese non-diabetic women. Xanthigen and Fucoxanthin also increased REE. This product may be considered a promising food supplement in the management of obesity.


Influence of a machined collar on crestal bone changes around titanium implants: a histometric study in the canine mandible.
It has been shown that peri-implant crestal bone reactions are influenced by both a rough-smooth implant border in one-piece, non-submerged, as well as an interface (microgap [MG] between implant/abutment) in two-piece butt-joint, submerged and non-submerged implants being placed at different levels in relation to the crest of the bone. According to standard surgical procedures, the rough-smooth implant border for implants with a smooth collar should be aligned with the crest of the bone exhibiting a smooth collar adjacent to peri-implant soft tissues. No data, however, are available for implants exhibiting a sandblasted, large-grit and acid-etched (SLA) surface all the way to the top of a non-submerged implant. Thus, the purpose of this study is to histometrically examine crestal bone changes around machined versus SLA-surfaced implant collars in a side-by-side comparison. A total of 60 titanium implants (30 machined collars and 30 SLA collars) were randomly placed in edentulous mandibular areas of five foxhounds forming six different subgroups (implant subgroups A to F). The implants in subgroups A to C had a machined collar (control), whereas the implants in subgroups D to F were SLA-treated all the way to the top (MG level; test). Furthermore, the MGs of the implants were placed at different levels in relation to the crest of the bone: the implants in subgroups A and E were 2 mm above the crest, in subgroups C and D 1 mm above, in subgroup B 3 mm above, and in subgroup F at the bone crest level. For all implants, abutment healing screws were connected the day of surgery. These caps were loosened and immediately retightened monthly. At 6 months, animals were sacrificed and non-decalcified histology was analyzed by evaluating peri-implant crestal bone levels. For implants in subgroup A, the estimated mean crestal bone loss (± SD) was -0.52 ± 0.40 mm; in subgroup B, +0.16 ± 0.40 mm (bone gain); in subgroup C, -1.28 ± 0.21 mm; in subgroup D, -0.43 ± 0.43 mm; in subgroup E, -0.03 ± 0.48 mm; and in subgroup F, -1.11 ± 0.27 mm. Mean bone loss for subgroup A was significantly greater than for subgroup E (P = 0.034) and bone loss for subgroup C was significantly greater than for subgroup D (P <0.001). Choosing a completely SLA-surfaced non-submerged implant can reduce the amount of peri-implant crestal bone loss and reduce the distance from the MG to the first bone-implant contact around unloaded implants compared to implants with a machined collar. Furthermore, a slightly exposed SLA surface during implant placement does not seem to compromise the overall hard and soft tissue integration and, in some cases, results in coronal bone formation in this canine model.


The effect of gamma-ray irradiation on the Mn(II) speciation in Deinococcus radiodurans and the potential role of Mn(II)-orthophosphates.
D. radiodurans accumulates large quantities of Mn(II), which is believed to form low molecular weight complexes with phosphate and metabolites that protect D. radiodurans from radiation damage. The concentration of Mn(II) species in D. radiodurans during the exponential and stationary phase was determined using high-field EPR and biochemical techniques. In the exponential growth phase cells a large fraction of the manganese was in the form of Mn(II)-orthophosphate complexes. By contrast, the intracellular concentration of these compounds in stationary phase cells was less than 16 μM, while that of Mn superoxide dismutase was 320 μM and that of another, yet unidentified, Mn(II) protein was 250 μM. Stationary cells were found to be equally resistant to irradiation as the exponential cells in spite of having significant lower Mn(II)-orthophosphate concentrations. Gamma irradiation induced no changes in the Mn(II) speciation. During stationary growth phase D. radiodurans favours the production of the two Mn-proteins over low molecular weight complexes suggesting that the latter were not essential for radio-resistance at this stage of growth.


Cytokine-mediated regulation of type IV collagenase expression and production in human trophoblast cells.
The invasive property of trophoblast cells is dependent on the activity of proteolytic enzymes of the metallo- and serine proteases family. Interleukin-1 (IL-1) was found to be involved in the regulation of these proteases in various systems, serving as an important modulator in trophoblast physiology (e.g. induction of hCG beta, cytokines, and others). Therefore, consideration is given in this report to the role of IL-1 in the regulation of metalloprotease activity in human trophoblasts. Human trophoblast cells were isolated from first trimester placentas by trypsin degradation and Percoll fractionation. Primary cell cultures of first trimester trophoblasts constitutively elaborated two species of collagenase type IV (92 and 72 kDa), as assessed in gelatin matrix. Treatment with IL-1 further augmented the 92-kDa type IV collagenase secretion in a dose-dependent manner. Furthermore, IL-1 significantly (P < 0.01) increased 92-kDa collagenase gene expression by trophoblast cells, as determined by solution hybridization/ribonuclease protection assay. Both the increase in gene expression and protein biosynthesis of the 92-kDa collagenase type IV were neutralized by the soluble IL-1 receptor, indirectly suggesting a receptor-mediated response. Interestingly, transforming growth factor-beta a putative modulator of IL-1 induced effects, was shown to induce the 92-kDa collagenase type IV secretion as well. These results provide indirect evidence supporting the idea that IL-1 and transforming growth factor-beta may play an intermediary role in trophoblast invasion at the feto-maternal interface by regulating trophoblast expression of 92-kDa type IV collagenase, a protease of prime importance in trophoblast invasion.


Antimitochondrial antibody recognition and structural integrity of the inner lipoyl domain of the E2 subunit of pyruvate dehydrogenase complex.
Antimitochondrial autoantibodies (AMAs), the serological hallmark of primary biliary cirrhosis, are directed against the lipoyl domain of the E2 subunit of pyruvate dehydrogenase (PDC-E2). However, comprehensive analysis of the amino acid residues of PDC-E2 lipoyl β-sheet with AMA specificity is lacking. In this study, we postulated that specific residues within the lipoyl domain are critical to AMA recognition by maintaining conformational integrity. We systematically replaced each of 19 residue peptides of the inner lipoyl domain with alanine and analyzed these mutants for reactivities against 60 primary biliary cirrhosis and 103 control sera. Based on these data, we then constructed mutants with two, three, or four replacements and, in addition, probed the structure of the substituted domains using thiol-specific spin labeling and electron paramagnetic resonance (EPR) of a (5)Ile→Ala and (12)Ile→Ala double mutant. Single alanine replacement at (5)Ile, (12)Ile, and (15)Glu significantly reduced AMA recognition. In addition, mutants with two, three, or four replacements at (5)Ile, (12)Ile, and (15)Glu reduced AMA reactivity even further. Indeed, EPR reveals a highly flexible structure within the (5)Ile and (12)Ile double-alanine mutant. Autoreactivity is largely focused on specific residues in the PDC-E2 lipoyl domain critical in maintaining the lipoyl loop conformation necessary for AMA recognition. Collectively, the AMA binding studies and EPR analysis demonstrate the necessity of the lipoyl β-sheet structural conformation in anti-PDC-E2 recognition.


In Vivo CT Analysis of Physiological Fibular Motion at the Level of the Ankle Syndesmosis During Plantigrade Weightbearing.
Background. It is clear that motion at the syndesmosis occurs due to ranging of the ankle joint, but the influence of weightbearing with the foot in the plantigrade position is unclear. In vivo computed tomographic (CT) evaluation of the syndesmosis has not been previously described. The purpose of this study is to quantify physiological fibular motion at the level of the ankle syndesmosis in both weightbearing and nonweightbearing conditions with the foot in the plantigrade position. Methods. CT images were obtained from 9 normal healthy subjects using a weightbearing CT imaging system. The subjects were positioned in a nonweightbearing and weightbearing state with their foot in the plantigrade position. Fibular translation and rotation were measured from the axial CT images using previously validated techniques. Results. Both the average lateral and anteroposterior translation of the fibula between weightbearing and nonweightbearing states was minimal (0.3 mm and 0.2 mm, respectively). The largest difference in translation observed in either direction was 0.9 mm. An average of 0.5° was found for rotational differences of the fibula between weightbearing and nonweightbearing. Neither of the translational and rotational parameters reached statistical significance. Conclusion. In vivo CT analysis of the distal tibiofibular joint with an intact syndesmosis did not reveal statistically significant physiological motion between weightbearing and nonweightbearing conditions with the foot in plantigrade position. Our findings suggest that weightbearing accounts for little motion at the syndesmosis and supports further investigation into the role of early protected weightbearing after syndesmosis fixation. Levels of Evidence: Level III: Case-control study.


3D Visual Tracking of an Articulated Robot in Precision Automated Tasks.
The most compelling requirements for visual tracking systems are a high detection accuracy and an adequate processing speed. However, the combination between the two requirements in real world applications is very challenging due to the fact that more accurate tracking tasks often require longer processing times, while quicker responses for the tracking system are more prone to errors, therefore a trade-off between accuracy and speed, and vice versa is required. This paper aims to achieve the two requirements together by implementing an accurate and time efficient tracking system. In this paper, an eye-to-hand visual system that has the ability to automatically track a moving target is introduced. An enhanced Circular Hough Transform (CHT) is employed for estimating the trajectory of a spherical target in three dimensions, the colour feature of the target was carefully selected by using a new colour selection process, the process relies on the use of a colour segmentation method (Delta E) with the CHT algorithm for finding the proper colour of the tracked target, the target was attached to the six degree of freedom (DOF) robot end-effector that performs a pick-and-place task. A cooperation of two Eye-to Hand cameras with their image Averaging filters are used for obtaining clear and steady images. This paper also examines a new technique for generating and controlling the observation search window in order to increase the computational speed of the tracking system, the techniques is named Controllable Region of interest based on Circular Hough Transform (CRCHT). Moreover, a new mathematical formula is introduced for updating the depth information of the vision system during the object tracking process. For more reliable and accurate tracking, a simplex optimization technique was employed for the calculation of the parameters for camera to robotic transformation matrix. The results obtained show the applicability of the proposed approach to track the moving robot with an overall tracking error of 0.25 mm. Also, the effectiveness of CRCHT technique in saving up to 60% of the overall time required for image processing.


Salmonella source attribution in a subtropical state of Australia: capturing environmental reservoirs of infection.
Salmonellosis is a leading cause of hospitalisation due to gastroenteritis in Australia. A previous source attribution analysis for a temperate state in Australia attributed most infections to chicken meat or eggs. Queensland is in northern Australia and includes subtropical and tropical climate zones. We analysed Queensland notifications for salmonellosis and conducted source attribution to compare reservoir sources with those in southern Australia. In contrast to temperate Australia, most infections were due to non-Typhimurium serotypes, with particularly high incidence in children under 5 years and strong seasonality, peaking in summer. We attributed 65.3% (95% credible interval (CrI) 60.6-73.2) of cases to either chicken meat or eggs and 15.5% (95% CrI 7.0-19.5) to nuts. The subtypes with the strongest associations with nuts were Salmonella Aberdeen, S. Birkenhead, S. Hvittingfoss, S. Potsdam and S. Waycross. All five subtypes had high rates of illness in children under 5 years (ranging from 4/100 000 to 23/100 000), suggesting that nuts may be serving as a proxy for environmental transmission in the model. Australia's climatic range allows us to conduct source attribution in different climate zones with similar food consumption patterns. This attribution provides evidence for environment-mediated transmission of salmonellosis in sub-tropical regions.


Cardiovascular disease burden due to productivity losses in European Society of Cardiology countries.
Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC). We used a standardised approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3·5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of €62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (€29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (€11 billion). Approximately 60% (€37 billion) of all productivity losses occurred in the 28 EU-member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries. Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases.


Cotton Fabric Coated with Conducting Polymers and its Application in Monitoring of Carnivorous Plant Response.
The paper describes the electrical plant response to mechanical stimulation monitored with the help of conducting polymers deposited on cotton fabric. Cotton fabric was coated with conducting polymers, polyaniline or polypyrrole, in situ during the oxidation of respective monomers in aqueous medium. Thus, modified fabrics were again coated with polypyrrole or polyaniline, respectively, in order to investigate any synergetic effect between both polymers with respect to conductivity and its stability during repeated dry cleaning. The coating was confirmed by infrared spectroscopy. The resulting fabrics have been used as electrodes to collect the electrical response to the stimulation of a Venus flytrap plant. This is a paradigm of the use of conducting polymers in monitoring of plant neurobiology.


Isolation and characterization of a new serodeme of Trypanosoma rhodesiense.
The isolation and characterization of a new serodeme of Trypanosoma brucei rhodesiense is described. A clone of organisms derived from a human infection produced chronic infections in mice. Additional clones of differing antigenic specificities were isolated from peaks of parasitemia which occurred in these mice. The variable antigen types (VATs) of these clones were determined by agglutination, immunofluorescence, and protection of actively immunized mice. Thirteen distinct VATs were isolated and designated Walter Reed Army Trypanozoon antigenic types. The described methodology and reagents, together with the chronicity of the infection produced in mice by this serodeme, provide a model for further study of immunopathology and antigenic variation in African trypanosomiasis. The use of these reagents in determining the incidence of VATs in an endemic area may allow an assessment of the feasibility of immunoprophylaxis.


Impact of naturally occurring serine/cysteine variations on the structure and function of Pseudomonas metallothioneins.
Metallothioneins (MTs), small cysteine-rich metal-binding proteins, support the viability of organisms under normal physiological conditions and help them to respond to different environmental stressors. Upon metal coordination (e.g. ZnII, CdII, CuI) they form characteristic polynuclear metal-thiolate clusters that are known for their high thermodynamic stability and kinetic lability. However, despite numerous studies, it is still not understood how MTs modulate their metal-binding properties. Pseudomonas MTs are an emerging subclass of bacterial MTs, distinct for their high number of His residues and for several unique features such as an intrinsically disordered long C-terminal tail and multiple variations in the number and nature of coordinating amino acids. These variations might provide the bacteria with a functional advantage derived from evolutionary adaptation to heterogeneous environments. Nearly 90% of the known Pseudomonas MT sequences feature a central YCC[combining low line]xxC motif, that is altered to YCS[combining low line]xxC in the rest. We demonstrate that the additional Cys residue serves as a coordinating ligand without influencing the metal-binding capacity, the overall metal-binding stability or the structure. However, the additional ligand changes intra-cluster dynamics and, as a consequence, modulates metal transfer reactions that could be functionally advantageous in vivo.


Psychiatric comorbidity of adolescents with sleep terrors or sleepwalking: a case-control study.
This study investigated the psychiatric comorbidity, personality traits and family history of adolescents with sleep terrors and/or sleepwalking. Thirty students with sleep terrors and/or sleepwalking and 30 classroom controls were selected on the basis of a sleep habit questionnaire. After completing the Junior Eysenck Personality Inventory (JEPI), the 60 subjects were interviewed by the first author with the Chinese-version Kiddie-SADS-E (Schedule for Affective Disorders and Schizophrenia for Children--Epidemiology Version). All subjects and their parents were interviewed for the subjects' sleep habits, sleep disorders, and personality characteristics in the previous year. The case and the control groups were divided based on whether the sleep terrors and/or sleepwalking had occurred in the previous year. There were 21 case and 30 control subjects in the final data analysis. The case group had more psychiatric diagnoses and problems; there were statistically significant differences in overanxious disorder, panic disorder, simple phobia and suicidal thoughts between the two groups. The case group had more sleeptalking and nightmares during the previous year as well as more enuresis in earlier years. From their parents' perspective, the case group was more nervous and pessimistic. The results of the JEPI showed a high neuroticism score in the case group. There was an increased familial occurrence of these two sleep disorders. Adolescents with sleep terrors and sleepwalking were found to have an increased prevalence of other sleep disorders, neurotic traits, and psychiatric disorders and problems. Whereas sleep terrors and sleepwalking in childhood are related primarily to genetic and developmental factors, their persistence and, especially, their onset in adolescence may be related to psychological factors.


Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis.
Adult structures in holometabolous insects such as Drosophila are generated by groups of imaginal cells dedicated to the formation of different organs. Imaginal cells are specified in the embryo and remain quiescent until the larval stages, when they proliferate and differentiate to form organs. The Drosophila tracheal system is extensively remodeled during metamorphosis by a small number of airway progenitors. Among these, the spiracular branch tracheoblasts are responsible for the generation of the pupal and adult abdominal airways. To understand the coordination of proliferation and differentiation during organogenesis of tubular organs, we analyzed the remodeling of Drosophila airways during metamorphosis. We show that the embryonic spiracular branch tracheoblasts are multipotent cells that express the homeobox transcription factor Cut, which is necessary for their survival and normal development. They give rise to three distinct cell populations at the end of larval development, which generate the adult tracheal tubes, the spiracle and the epidermis surrounding the spiracle. Our study establishes the series of events that lead to the formation of an adult tubular structure in Drosophila.


Partial validation of the Dutch model for emission and transport of nutrients (STONE).
The Netherlands has to cope with large losses of N and P to groundwater and surface water. Agriculture is the dominant source of these nutrients, particularly with reference to nutrient excretion due to intensive animal husbandry in combination with fertilizer use. The Dutch government has recently launched a stricter eutrophication abatement policy to comply with the EC nitrate directive. The Dutch consensus model for N and P emission to groundwater and surface water (STONE) has been developed to evaluate the environmental benefits of abatement plans. Due to the possibly severe socioeconomic consequences of eutrophication abatement plans, it is of utmost importance that the model is thoroughly validated. Because STONE is applied on a nationwide scale, the model validation has also been carried out on this scale. For this purpose the model outputs were compared with lumped results from monitoring networks in the upper groundwater and in surface waters. About 13,000 recent point source observations of nitrate in the upper groundwater were available, along with several hundreds of observations showing N and P in local surface water systems. Comparison of observations from the different spatial scales available showed the issue of scale to be important. Scale issues will be addressed in the next stages of the validation study.


Domains of the TCR beta-chain required for early thymocyte development.
The T cell receptor beta (TCR beta) chain controls the developmental transition from CD4-CD8- to CD4+8+thymocytes. We show that the extracellular constant region and the transmembrane region, but not the variable domain or cytoplasmic tail of the TCR beta chain are required for this differentiation step. TCR beta mutant chains lacking the cytoplasmic tail can be found at the cell surface both in functional TCR/CD3 complexes and in a GPI-anchored monomeric form indicating that the cytoplasmic tail of the TCR beta chain functions as an ER retention signal. The concordance between cell surface expression of the mutant chains as TCR/CD3 complexes and their capacity to mediate thymocyte differentiation supports the CD3 mediated feedback model in which preTCR/CD3 complexes control the developmental transition from CD4-CD8- to CD4+CD8+thymocytes.


A novel Dps-type protein from insect gut bacteria catalyses hydrolysis and synthesis of N-acyl amino acids.
A novel type of a microbial N-acyl amino acid hydrolase (AAH) from insect gut bacteria was purified, cloned and functionally characterized. The enzyme was obtained from Microbacterium arborescens SE14 isolated from the foregut of larvae of the generalist herbivore Spodoptera exigua. The substrates of AAH are N-acyl-glutamines previously reported to elicit plant defence reactions after introduction into the leaf during feeding. The isolated AAH catalyses the hydrolysis of the amide bond (K(m) = 36 micromol l(-1)) and, less efficient, the formation (K(m) = 3 mmol l(-1)) of the elicitor active N-acyl amino acids. The AAH from M. arborescens SE14 shows no homology to known fatty acyl amidases (EC 220.127.116.11) but belongs to the family of Dps proteins (DNA-binding protein from starved cell). In line with other DPS proteins AAH is a homododecamer (monomer 17 181 Da) and contains iron atoms (c. 1-16 iron atoms per subunit). Unlike genuine DPS proteins the enzyme does not significantly bind DNA. Amino acid hydrolase is the first member of the DPS family that catalyses the cleavage or formation of amide bonds. The participation of a microbial enzyme in the homeostasis of N-acyl-glutamines in the insect gut adds further complexity to the interaction between plants and their herbivores.


Effect of rNA interference on Oatp3a1 gene expression on biological characteristics and immune factors of ovarian granulosa cells in rats with PCOS.
Polycystic ovary syndrome (PCOS) is a common endocrinal metabolic disease, and its pathogenesis has not yet been thoroughly studied. The purpose of this experiment was to investigate the effect of RNA interference on Oatp3a1 gene expression on the biological viability and immune factors of ovarian granulosa cells in rats with PCOS. First, rats were intragastrically administered 1 mg/kg letrozole to successfully construct PCOS model. Western blot, qRT-PCR, CCK8 and flow cytometry were used to detect the gene expression, immune factor protein expression, cell proliferation and apoptosis in ovarian granulosa cells transfected with siRNA Oatp3a1 in rats with PCOS, respectively. The results showed that follicle stimulating hormone receptor (FSHR) was located on the cell membrane of rat ovarian granulosa cells, and letrozole successfully induced PCOS rat model. In PCOS rat ovarian granulosa cells, the mRNA expression level of Oapta1 was higher than that in normal rat ovarian granulosa cells. At the same time, compared with the sham group, the protein expression of NF-κB, TGF-β1 and VEGF in si-Oatp3a1 group was significantly down-regulated (P < 0.05), and the cell proliferation rate was significantly decreased in si-Oatp3a1 group (P < 0.05) in comparison with the sham group. The apoptotic rate was increased obviously (P < 0.05), which was about 2.5 times that of the sham group. This indicates that in the ovarian granulosa cells of rats with PCOS, the interference of Oatp3a1 gene expression can significantly inhibit cell proliferation and promote apoptosis, while inhibiting the expression of immune factors TGF-β1 and VEGF can reduce the expression of NF-κB protein, thereby suppressing the activation of the NF-κB signaling pathway.


Idiosyncratic perception: a link between acuity, perceived position and apparent size.
Perceiving the positions of objects is a prerequisite for most other visual and visuomotor functions, but human perception of object position varies from one individual to the next. The source of these individual differences in perceived position and their perceptual consequences are unknown. Here, we tested whether idiosyncratic biases in the underlying representation of visual space propagate across different levels of visual processing. In Experiment 1, using a position matching task, we found stable, observer-specific compressions and expansions within local regions throughout the visual field. We then measured Vernier acuity (Experiment 2) and perceived size of objects (Experiment 3) across the visual field and found that individualized spatial distortions were closely associated with variations in both visual acuity and apparent object size. Our results reveal idiosyncratic biases in perceived position and size, originating from a heterogeneous spatial resolution that carries across the visual hierarchy.


Different adaptations in AMPA receptor transmission in the nucleus accumbens after short vs long access cocaine self-administration regimens.
Ca(2+)-permeable AMPA receptors (CP-AMPARs) accumulate in the nucleus accumbens (NAc) after ∼1 month of withdrawal from a long-access cocaine self-administration regimen (6 h/d, 10d). This is functionally significant because CP-AMPARs mediate the 'incubated' cue-induced cocaine craving produced by this regimen. Our present goal was to determine if other commonly employed cocaine self-administration regimens also elicit CP-AMPAR accumulation. We compared four regimens, named according to whether sessions were short-access (ShA, 2 h) or long-access (LgA, 6 h) and the total number of sessions: LgA/10d (already shown to elicit CP-AMPAR accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latter regimens, rats began with 10 days of ShA and then entered a differential phase (10-14 days) in which ShA sessions either continued or switched to LgA. Controls self-administered saline. After >40 days of withdrawal, whole-cell patch-clamp recordings were performed in NAc core medium spiny neurons to assess the contribution of CP-AMPAR transmission, based on the magnitude of synaptic suppression elicited by bath application of the selective CP-AMPAR antagonist naspm (100 μM). Naspm produced a non-significant (∼10%) attenuation of electrically evoked local excitatory postsynaptic current in the saline and ShA groups. By contrast, a significant naspm-induced synaptic attenuation (25-30%) was observed in both the LgA groups. Further analyses indicate that this emergence of CP-AMPAR transmission in the LgA groups is associated with increased baseline responsiveness of MSN to excitatory drive. Together with data on cocaine infusions in each group, our results show that CP-AMPAR accumulation and enhanced glutamate transmission is associated with longer sessions (6 h), rather than the number of sessions or cocaine infusions.


Mapping temporo-parietal and temporo-occipital cortico-cortical connections of the human middle longitudinal fascicle in subject-specific, probabilistic, and stereotaxic Talairach spaces.
Originally, the middle longitudinal fascicle (MdLF) was defined as a long association fiber tract connecting the superior temporal gyrus and temporal pole with the angular gyrus. More recently its description has been expanded to include all long postrolandic cortico-cortical association connections of the superior temporal gyrus and dorsal temporal pole with the parietal and occipital lobes. Despite its location and size, which makes MdLF one of the most prominent cerebral association fiber tracts, its discovery in humans is recent. Given the absence of a gold standard in humans for this fiber tract, its precise and complete connectivity remains to be determined with certainty. In this study using high angular resolution diffusion MRI (HARDI), we delineated for the first time, six major fiber connections of the human MdLF, four of which are temporo-parietal and two temporo-occipital, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy brains. Considering the cortical affiliations of the different connections of MdLF we suggested that this fiber tract may be related to language, attention and integrative higher level visual and auditory processing associated functions. Furthermore, given the extensive connectivity provided to superior temporal gyrus and temporal pole with the parietal and occipital lobes, MdLF may be involved in several neurological and psychiatric conditions such as primary progressive aphasia and other aphasic syndromes, some forms of behavioral variant of frontotemporal dementia, atypical forms of Alzheimer's disease, corticobasal degeneration, schizophrenia as well as attention-deficit/hyperactivity Disorder and neglect disorders.


Performance of the Multidimensional Geriatric Assessment and Multidimensional Prognostic Index in predicting negative outcomes in older adults with cancer.
The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.


Cardiovascular risk of patients with gout seen at rheumatology clinics following a structured assessment.
Gout-associated cardiovascular (CV) risk relates to comorbidities and crystal-led inflammation. The aim was to estimate the CV risk by prediction tools in new patients with gout and to assess whether ultrasonographic carotid changes are present in patients without high CV risk. Cross-sectional study. Consecutive new patients with crystal-proven gout underwent a structured CV consultation, including CV events, risk factors and two risk prediction tools-the Systematic COronary Evaluation (SCORE) and the Framingham Heart Study (FHS). CV risk was stratified according to current European guidelines. Carotid ultrasound (cUS) was performed in patients with less than very high CV risk. The presence of carotid plaques was studied depending on the SCORE and FHS by the area under the curve (AUC) of receiver operating curves. 237 new patients with gout were recruited. CV stratification by scores showed a predominance of very high (95 patients, 40.1%) and moderate (72 patients, 30.5%) risk levels. cUS was performed in 142 patients, finding atheroma plaques in 66 (46.5%, 95% CI 37.8 to 54.2). Following cUS findings, patients classified as very high risk increased from 40.1% up to 67.9% (161/237 patients). SCORE and FHS predicted moderately (AUC 0.711 and 0.683, respectively) the presence of atheroma plaques at cUS. The majority of patients presenting with gout may be at very high CV risk, indicating the need for initiating optimal prevention strategies at this stage. Risk prediction tools appear to underestimate the presence of carotid plaque in patients with gout.


Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement.
Advances in modern sequencing technologies allow us to generate sufficient data to analyze hundreds of bacterial genomes from a single machine in a single day. This potential for sequencing massive numbers of genomes calls for fully automated methods to produce high-quality assemblies and variant calls. We introduce Pilon, a fully automated, all-in-one tool for correcting draft assemblies and calling sequence variants of multiple sizes, including very large insertions and deletions. Pilon works with many types of sequence data, but is particularly strong when supplied with paired end data from two Illumina libraries with small e.g., 180 bp and large e.g., 3-5 Kb inserts. Pilon significantly improves draft genome assemblies by correcting bases, fixing mis-assemblies and filling gaps. For both haploid and diploid genomes, Pilon produces more contiguous genomes with fewer errors, enabling identification of more biologically relevant genes. Furthermore, Pilon identifies small variants with high accuracy as compared to state-of-the-art tools and is unique in its ability to accurately identify large sequence variants including duplications and resolve large insertions. Pilon is being used to improve the assemblies of thousands of new genomes and to identify variants from thousands of clinically relevant bacterial strains. Pilon is freely available as open source software.


Time-course morphological and functional disorders of the kidney induced by long-term high-fat diet intake in female rats.
Evidence is emerging that highlights the far-reaching consequences of a high-fat diet (HFD) on kidney morphology and function disorders. The present study was performed on 3-, 5-, 7- and 9-week-old HFD female rats compared with the appropriate gender and age-matched animals. We evaluated the kidney expression of angiotensin type II receptor and fibrotic and epithelial-to-mesenchymal transition (EMT) markers, by immunoblotting and immunohistochemical and histological techniques, in parallel with kidney function. In the current study, the time-course HFD-treated group showed, by immunoblotting and immunohistochemical analysis, an early time-course increase in the expression of transforming growth factor β-1 (TGFβ-1) in the entire kidney of HFD-treated rats, compared with that observed in the control group. Simultaneously, the study shows a transient increase in the expression of ZEB2 in the HFD whole kidney accompanied by a fall in the E-cadherin expression and increased collagen and fibronectin deposition. A pronounced decrease in fractional urinary sodium excretion was also demonstrated in the long-term HFD-treated rats. The decreased FENa(+) was accompanied by a fall in FEPNa(+) and FEPPNa(+), which occurred in association with significantly decreased CCr and, certainly on the sodium-filtered load. The reduction in the glomerular filtration rate (GFR) occurred in parallel to proteinuria and glomerular desmin overexpression. The results of the current study suggest that podocyte injury in parallel with observed proteinuria and evidence of EMT transformation are associated with long-term loss of kidney function and renal sodium and water retention.


The effect of prior exposure to imatinib on transplant-related mortality.
Imatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, relapse is common in patients with advanced or high risk disease. Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT. We retrospectively analyzed 70 patients with CML and 21 with Ph+ ALL who had received imatinib prior to SCT. Data were retrieved by directly contacting centers. Multivariate analysis was used to define factors associated with major outcomes (engraftment, graft-versus-host disease, relapse, non-relapse mortality) in addition to descriptive statistics. For the CML patients major outcomes were compared with those of historical controls drawn from the EBMT registry. At SCT, 44% of CML patients were in accelerated phase or blast crisis and 40% of ALL patients had active disease compared to 84% and 95% prior to imatinib. At 24 months, estimated transplant-related mortality was 44% and estimated relapse mortality 24%. Factors associated with shorter overall and progression-free survival were advanced disease at SCT and a female donor/male recipient pairing. No unusual organ toxicities were observed. Compared to historical controls, prior imatinib treatment did not influence overall survival, progression-free survival or non-relapse mortality, while there was a trend towards higher relapse mortality and significantly less chronic graft-versus-host disease. Within the limits of a heterogeneous and relatively small cohort of patients, we found no evidence that imatinib negatively affects major outcomes after SCT, suggesting that imatinib prior to SCT is safe.