Role of thyroid hormone during early brain development.
The present comments are restricted to the role of maternal thyroid hormone on early brain development, and are based mostly on information presently available for the human fetal brain. It emphasizes that maternal hypothyroxinemia - defined as thyroxine (T4) concentrations that are low for the stage of pregnancy - is potentially damaging for neurodevelopment of the fetus throughout pregnancy, but especially so before midgestation, as the mother is then the only source of T4 for the developing brain. Despite a highly efficient uterine-placental 'barrier' to their transfer, very small amounts of T4 and triiodothyronine (T3) of maternal origin are present in the fetal compartment by 4 weeks after conception, with T4 increasing steadily thereafter. A major proportion of T4 in fetal fluids is not protein-bound: the 'free' T4 (FT4) available to fetal tissues is determined by the maternal serum T4, and reaches concentrations known to be of biological significance in adults. Despite very low T3 and 'free' T3 (FT3) in fetal fluids, the T3 generated locally from T4 in the cerebral cortex reaches adult concentrations by midgestation, and is partly bound to its nuclear receptor. Experimental results in the rat strongly support the conclusion that thyroid hormone is already required for normal corticogenesis very early in pregnancy. The first trimester surge of maternal FT4 is proposed as a biologically relevant event controlled by the conceptus to ensure its developing cerebral cortex is provided with the necessary amounts of substrate for the local generation of adequate amounts of T3 for binding to its nuclear receptor. Women unable to increase their production of T4 early in pregnancy would constitute a population at risk for neurological disabilities in their children. As mild-moderate iodine deficiency is still the most widespread cause of maternal hypothyroxinemia in Western societies, the birth of many children with learning disabilities may already be preventable by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible.


Retinal cryopexy stimulates traction retinal detachment formation in the presence of an ocular wound.
Pigmented rabbits were treated with retinal cryopexy applied to 180 degrees of the peripheral inferior retina in one eye, and then a 6-mm full-thickness circumferential wound was made in both eyes 3 mm posterior to the superior limbus. The wounds were sutured, and only eyes with minimal vitreous hemorrhage and no retinal breaks were included in the study. Eyes were then examined with indirect ophthalmoscopy on postoperative days 1, 7, 14, 21, and 28. Of eyes that received cryopexy and an ocular wound (n = 13), the retina in three became totally detached between postoperative days 14 and 28; seven eyes had traction retinal detachment first noted on postoperative day 14 that did not become total by postoperative day 28; and two retinas remained attached, but showed folds suggesting the presence of epiretinal membranes. One retina remained attached without folding. In eyes that received only an ocular wound (n = 13), the retina in one showed folds, and in 12 eyes it remained attached with no evidence of epiretinal membrane formation. Retinas treated with cryopexy alone (n = 4) remained attached without folds. On postoperative day 28, the rabbits were killed, and, after fixation, eyes were examined grossly and by light and electron microscopy. Examination confirmed the presence of vitreous and epiretinal cellular membranes in eyes with retinal detachment. These data suggest that in the presence of an ocular wound, retinal cryopexy, which has previously been shown to cause extensive breakdown of the blood-retinal barrier, stimulates the formation of intraocular cellular membranes and traction retinal detachment.


Cloning and characterization of RLPK, a novel RSK-related protein kinase.
A novel protein kinase whose activity can be stimulated by mitogen in vivo was cloned and characterized. The cDNA of this gene encodes an 802-amino acid protein (termed RLPK) with the highest homology (37% identity) to the two protein kinase families, p90(RSK) and p70(RSK). Like p90(RSR), but not p70(RSK), RLPK also contains two complete nonidentical protein kinase domains. RLPK mRNA is widely expressed in all human tissues examined and is enriched in the brain, heart, and placenta. In HeLa cells, transiently expressed epitope-tagged RLPK can be strongly induced by epidermal growth factor, serum, and phorbol 12-myristate 13-acetate, but only moderately up-regulated by tumor necrosis factor-alpha and other stress-related stimuli. The activity of RLPK stimulated by epidermal growth factor was not inhibited by several known protein kinase C inhibitors nor by rapamycin, a known specific inhibitor for p70(RSK), but could be inhibited by herbimycin A, a tyrosine kinase inhibitor, and partially inhibited by PD98059 or SB203580, inhibitors for the mitogen-activated protein kinase pathways. Recombinant RLPK possesses high phosphorylation activity toward histone 2B and the S6 peptide, RRRLSSLRA. Although purified recombinant RLPK can be phosphorylated by ERK2 and p38alpha in vitro, its activity is not affected by this phosphorylation. Moreover, the treatment of RLPK with acid phosphatase did not reduce its in vitro kinase activity. These data suggest that RLPK is structurally similar to previously isolated RSKs, but its regulatory mechanism may be distinct from either p70(RSK) or p90(RSK)s.


Detection of Illicit Drugs by Trained Honeybees (Apis mellifera).
Illegal drugs exacerbate global social challenges such as substance addiction, mental health issues and violent crime. Police and customs officials often rely on specially-trained sniffer dogs, which act as sensitive biological detectors to find concealed illegal drugs. However, the dog "alert" is no longer sufficient evidence to allow a search without a warrant or additional probable cause because cannabis has been legalized in two US states and is decriminalized in many others. Retraining dogs to recognize a narrower spectrum of drugs is difficult and training new dogs is time consuming, yet there are no analytical devices with the portability and sensitivity necessary to detect substance-specific chemical signatures. This means there is currently no substitute for sniffer dogs. Here we describe an insect screening procedure showing that the western honeybee (Apis mellifera) can sense volatiles associated with pure samples of heroin and cocaine. We developed a portable electroantennographic device for the on-site measurement of volatile perception by these insects, and found a positive correlation between honeybee antennal responses and the concentration of specific drugs in test samples. Furthermore, we tested the ability of honeybees to learn the scent of heroin and trained them to show a reliable behavioral response in the presence of a highly-diluted scent of pure heroin. Trained honeybees could therefore be used to complement or replace the role of sniffer dogs as part of an automated drug detection system. Insects are highly sensitive to volatile compounds and provide an untapped resource for the development of biosensors. Automated conditioning as presented in this study could be developed as a platform for the practical detection of illicit drugs using insect-based sensors.


Normal appearance of arachnoid granulations on contrast-enhanced CT and MR of the brain: differentiation from dural sinus disease.
To determine the imaging appearance and frequency with which arachnoid granulations are seen on contrast-enhanced CT and MR studies of the brain. We retrospectively reviewed 573 contrast-enhanced CT scans and 100 contrast-enhanced MR studies of the brain for the presence of discrete filling defects within the venous sinuses. An anatomic study of the dural sinuses of 29 cadavers was performed, and the location, appearance, and histologic findings of focal protrusions into the dural sinus lumen (arachnoid granulations) were assessed and compared with the imaging findings. Discrete filling defects within the dural sinuses were found on 138 (24%) of the contrast-enhanced CT examinations. A total of 168 defects were found, the majority (92%) within the transverse sinuses. One third were isodense and two thirds were hypodense relative to brain parenchyma. Patients with filling defects were older than patients without filling defects (mean age, 46 years versus 40 years). Discrete intrasinus signal foci were noted on 13 (13%) of the contrast-enhanced MR studies. The foci followed the same distribution as the filling defects seen on CT scans and were isointense to hypointense on T1-weighted images, variable in signal on balanced images, and hyperintense on T2-weighted images. Transverse sinus arachnoid granulations were noted adjacent to venous entrance sites in 62% and 85% of the CT and MR examinations, respectively. Arachnoid granulations were found in 19 (66%) of the cadaveric specimens, in a similar distribution as that seen on the imaging studies. Discrete filling defects, consistent with arachnoid granulations, may be seen in the dural sinuses on 24% of contrast-enhanced CT scans and on 13% of MR studies. They are focal, well-defined, and typically located within the lateral transverse sinuses adjacent to venous entrance sites. They should not be mistaken for sinus thrombosis or intrasinus tumor, but recognized as normal structures.


A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition.
HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this "minimal" mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.


Cation-independent mannose 6-phosphate receptor: From roles and functions to targeted therapies.
The cation-independent mannose 6-phosphate receptor (CI-M6PR) is a ubiquitous transmembrane receptor whose main intracellular role is to direct enzymes carrying mannose 6-phosphate moieties to lysosomal compartments. Recently, the small membrane-bound portion of this receptor has appeared to be implicated in numerous pathophysiological processes. This review presents an overview of the main ligand partners and the roles of CI-M6PR in lysosomal storage diseases, neurology, immunology and cancer fields. Moreover, this membrane receptor has already been noted for its strong potential in therapeutic applications thanks to its cellular internalization activity and its ability to address pathogenic factors to lysosomes for degradation. A number of therapeutic delivery approaches using CI-M6PR, in particular with enzymes, antibodies or nanoparticles, are currently being proposed.


A human endogenous retrovirus suppresses translation of an associated fusion transcript, PLA2L.
Human endogenous retroviruses (HERVs) are repetitive, noninfectious chromosomal elements degenerated from exogenous retroviruses. The HERV-H family is composed of approximately 1,000 elements which are dispersed throughout the human genome. We have shown previously that an HERV-H element splices into a downstream locus, termed PLA2L, which has a large open reading frame (ORF) containing two domains with phospholipase A2 homology. Over half of the putative 5' untranslated region (5' UTR) of the resulting fusion transcript is derived from HERV-H long-terminal-repeat and internal sequences. As 5' UTRs are known to modulate translation initiation, we tested for possible effects upon gene expression at the translation level due to the 5' fusion with HERV-H sequences. No PLA2L protein was detected in teratocarcinoma cell lines in which PLA2L mRNA is abundantly expressed. In addition, despite a high level of transcription, no protein synthesis was detected when the full-length PLA2L cDNA was expressed in COS cells. Upon removal of the 5'-terminal HERV-H sequences, PLA2L protein was seen in transfectants. The 5' UTR contains both small ORFs and a strong predicted RNA secondary structure, both of which have been shown to contribute to translation suppression. The HERV-H sequences, combined with a unique PLA2L 5' UTR sequence, form a predicted RNA stem-loop that has a stability greater than that proposed to negatively affect translation. Interestingly, this stem-loop is abolished when the HERV-H sequences are removed. We hypothesize that the PLA2L 5' HERV-H sequences function as an abnormally long and complex 5' UTR, resulting in suppression of translation in both teratocarcinoma cell lines and full-length cDNA transfectants. This is the first known example of a endogenous retrovirus integration affecting expression of a heterologous human gene at the translational level.


A novel phage genome integrated into a plasmid in Bacillus thuringiensis strain AF101.
Bacillus thuringiensis strain AF101 possesses a single plasmid (pAF101) with a molecular size of 42 MDa (69 kb). During plasmid curing experiments in strain AF101, we found that a phage (J7W-1) was induced by ethidium bromide treatment. Moreover, the phage genome (48 kb) hybridized only with pAF101 on a Southern blot of the DNA of a cleared lysate prepared from strain AF101. Comparison of the restriction patterns of pAF101 and J7W-1 phage DNA revealed that pAF101 contains not only the entire phage DNA but also a plasmid-specific DNA region. These results indicate that the J7W-1 genome has been stably integrated into pAF101 in strain AF101. Integration of the J7W-1 genome into a plasmid was also observed after phage infection of the type strain of B. thuringiensis subsp. israelensis.


Membrane cholesterol modulates the fluid shear stress response of polymorphonuclear leukocytes via its effects on membrane fluidity.
Continuous exposure of polymorphonuclear leukocytes (PMNLs) to circulatory hemodynamics points to fluid flow as a biophysical regulator of their activity. Specifically, fluid flow-derived shear stresses deactivate leukocytes via actions on the conformational activities of proteins on the cell surface. Because membrane properties affect activities of membrane-bound proteins, we hypothesized that changes in the physical properties of cell membranes influence PMNL sensitivity to fluid shear stress. For this purpose, we modified PMNL membranes and showed that the cellular mechanosensitivity to shear was impaired whether we increased, reduced, or disrupted the organization of cholesterol within the lipid bilayer. Notably, PMNLs with enriched membrane cholesterol exhibited attenuated pseudopod retraction responses to shear that were recovered by select concentrations of benzyl alcohol (a membrane fluidizer). In fact, PMNL responses to shear positively correlated (R(2) = 0.96; P < 0.0001) with cholesterol-related membrane fluidity. Moreover, in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice fed a high-fat diet (a hypercholesterolemia model), PMNL shear-responses correlated (R(2) = 0.5; P < 0.01) with blood concentrations of unesterified (i.e., free) cholesterol. In this regard, the shear-responses of PMNLs gradually diminished and eventually reversed as free cholesterol levels in blood increased during 8 wk of the high-fat diet. Collectively, our results provided evidence that cholesterol is an important component of the PMNL mechanotransducing capacity and elevated membrane cholesterol impairs PMNL shear-responses at least partially through its impact on membrane fluidity. This cholesterol-linked perturbation may contribute to dysregulated PMNL activity (e.g., chronic inflammation) related to hypercholesterolemia and causal for cardiovascular pathologies (e.g., atherosclerosis).


Clinical symptoms and myocardial infarction in left bundle branch block patients.
In patients with left bundle branch block (LBBB) and acute chest pain, the association between the clinical presentation and the diagnosis of myocardial infarction has not been investigated. We sought to identify features in the clinical history of patients with LBBB and acute cardiopulmonary symptoms that predict myocardial infarction among candidates for reperfusion therapy. We retrospectively studied a consecutive cohort of 75 patients (94 presentations) who presented to a university emergency department from 1994 to 1997 with LBBB on initial electrocardiogram (ECG) and acute chest pain of >/=20 min duration or acute pulmonary edema. Among the 94 presentations meeting criteria for the cohort, 26 (28%) had confirmed myocardial infarction. Coronary heart disease risk factors, past cardiac history, prior LBBB on the ECG, and presenting symptoms did not predict whether patients were having myocardial infarction. The clinical history was not effective at distinguishing LBBB patients with myocardial infarction among patients who appeared to be candidates for acute reperfusion therapy.


Ubiquitin Associated Protein 2-Like (UBAP2L) Overexpression in Patients with Hepatocellular Carcinoma and its Clinical Significance.
BACKGROUND Recently, accumulating studies have shown that ubiquitin associated protein 2-like (UBAP2L) is overexpressed in many kinds of malignant tumors, which is closely associated to tumor growth and metastasis. However, the correlations of UBAP2L expression with clinicopathological factors and prognosis of hepatocellular carcinoma (HCC) patients still remain unclear. MATERIAL AND METHODS Bioinformatics database (GEO and TCGA) and our own experimental results (including immunohistochemical staining, western blotting and real-time PCR) were analyzed to validate the expression levels of UBAP2L in HCC. Furthermore, Kaplan-Meier survival analysis and Cox multivariate regression model were used to demonstrate the associations of UBAP2L expression with clinicopathological factors and prognosis of HCC patients. Additionally, the potential underlying mechanisms associated to angiogenesis were preliminarily explored. RESULTS Compared to the normal group, UBAP2L was significantly highly expressed in HCC cell lines and tissues. Kaplan-Meier survival analysis revealed that patients with high UBAP2L expression level had dramatically less survival time than those with low UBAP2L expression level (p=0.000). Moreover, multivariate Cox regression analysis showed that UBAP2L high expression was an independently unfavorable prognostic parameter for OS of HCC patients (p=0.000). Additionally, Pearson correlation analysis showed that the relationship between UBAP2L expression and VEGF or MVD was significantly positive, respectively (r=0.460, p=0.000 and r=0.387, p=0.000). CONCLUSIONS UBAP2L was overexpressed in HCC, and patients with high UBAP2L expression had unfavorable prognosis. UBAP2L could be a new potential therapeutic target for HCC in the future.


Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses.
Genetic variation plays a substantial role in variation in strength, but the underlying mechanisms remain poorly understood. The objective of the present study was to examine the mechanisms underlying variation in muscle mass, a predictor of strength, between LG/J and SM/J strains, which are the inbred progeny of mice selected, respectively, for high and low body weight. We measured weight of five hindlimb muscles in LG/J and SM/J males and females, in F(1) and F(2) intercrosses, and in an advanced intercross (AI), F(34), between the two. F(2) mice were genotyped using 162 SNPs throughout the genome; F(34) mice were genotyped at 3,015 SNPs. A twofold difference in muscle mass between the LG/J and SM/J mouse strains was observed. Integrated genome-wide association analysis in the combined population of F(2) and AI identified 22 quantitative trait loci (QTL; genome-wide P < 0.05) affecting muscle weight on Chr 2 (2 QTL), 4, 5, 6 (7 QTL), 7 (4 QTL), 8 (4 QTL), and 11 (3 QTL). The LG/J allele conferred greater muscle weight in all cases. The 1.5-LOD QTL support intervals ranged between 0.3 and 13.4 Mb (median 3.7 Mb) restricting the list of candidates to between 5 and 97 genes. Selection for body weight segregated the alleles affecting skeletal muscle, the most abundant tissue in the body. Combination of analyses in an F(2) and AI was an effective strategy to detect and refine the QTL in a genome-wide manner. The achieved resolution facilitates further elucidation of the underlying genetic mechanisms affecting muscle mass.


[Acute psychotic productivity in cerebral imaging].
Regional cerebral blood flow (rCBF) was analysed in 24 neuroleptically never treated schizophrenics by 99m-Tc-HMPAO-SPECT. Psychopathological symptoms (PANSS) were correlated with rCBF-measures using multidimensional scaling (MDS). Highest degrees of correlation were found for ideas of grandiosity and formal thought disorders compared to different regions of interest (ROIs). An adynamic cluster was defined by basic symptoms which showed signs of deficiency. This cluster was by the highest degree correlated with a cluster defined by rCBF compared to four different clusters of basic symptoms. A fMRI-study was performed in schizophrenic patients with auditive hallucinations in comparison to healthy controls. We offered simple acoustic stimuli perceived as coming from the outside versus inside. For the outside condition, controls activated the medial temporal gyrus on the left side and the rightsided precuneus and postcentral gyrus which represent the auditive source locating and the stimulus processing systems, for inside, they activated the left insula. Hallucinating schizophrenic neither activated the one nor the other system. We discussed the findings as a possible explanation of the schizophrenics' tendency to misinterpret hallucinations as real perceptions.


Common plasmid encoding resistance to ampicillin, chloramphenicol, gentamicin, and trimethoprim-sulfadiazine in two serotypes of Salmonella isolated during an outbreak of equine salmonellosis.
An outbreak of equine salmonellosis occurred at the Veterinary Medical Teaching Hospital, University of California, Davis, between June 1981 and March 1982. Forty-four horses were infected with Salmonella saint-paul, a serotype rarely isolated from animals at the university before the outbreak. Unlike the isolates of S saint-paul obtained at the beginning of the outbreak, almost all strains isolated near the end were resistant to ampicillin, cephalothin, chloramphenicol, gentamicin, kanamycin, sulfadiazine, trimethoprim, and trimethoprim-sulfadiazine. A conjugal-resistance plasmid (R-plasmid) was responsible for resistance to these antimicrobics. This R-plasmid was identical to an R-plasmid of S krefeld, a serotype that had been isolated repeatedly throughout the hospital before, during, and after the outbreak involving S saint-paul. This finding prompted the suggestion that in vivo transfer of the R-plasmid had occurred. Whether the donor organism was S krefeld is unknown.


Multiinstitutional Analysis of Thyroid Nodule Risk Stratification Using the American College of Radiology Thyroid Imaging Reporting and Data System.
Guidelines for managing thyroid nodules are highly dependent on risk stratification based on sonographic findings. The purpose of this study is to evaluate the risk stratification system used by the American College of Radiology Thyroid Imaging Reporting and Data System (TIRADS). Patients with thyroid nodules who underwent sonography and fine-needle aspiration were enrolled in a multiinstitutional study. The sonographic nodule features evaluated in the study were composition, echogenicity, margins, and echogenic foci. Images were reviewed by two radiologists who were blinded to the results of cytologic analysis. Nodules were assigned points for each feature, and the points were totaled to determine the final TIRADS level (TR1-TR5). The risk of cancer associated with each point total and final TIRADS level was determined. A total of 3422 nodules, 352 of which were malignant, were studied. The risk of malignancy was closely associated with the composition, echogenicity, margins, and echogenic foci of the nodules (p < 0.0001, in all cases). An increased aggregate risk of nodule malignancy was noted as the TIRADS point level increased from 0 to 10 (p < 0.0001) and as the final TIRADS level increased from TR1 to TR5 (p < 0.0001). Of the 3422 nodules, 2948 (86.1%) had risk levels that were within 1% of the TIRADS risk thresholds. Of the 474 nodules that were more than 1% outside these thresholds, 88.0% (417/474) had a risk level that was below the TIRADS threshold. The aggregate risk of malignancy for nodules associated with each individual TIRADS point level (0-10) and each final TIRADS level (TR1-TR5) falls within the TIRADS risk stratification thresholds. A total of 85% of all nodules were within 1% of the specified TIRADS risk thresholds.


Reading ability and reading engagement in older adults with glaucoma.
We evaluated the impact of glaucoma-related vision loss on reading ability and reading engagement in 10 reading activities. A total of 63 glaucoma patients and 59 glaucoma suspect controls self-rated their level of reading difficulty for 10 reading items, and responses were analyzed using Rasch analysis to determine reading ability. Reading engagement was assessed by asking subjects to report the number of days per week they engaged in each reading activity. Reading restriction was determined as a decrement in engagement. Glaucoma subjects more often described greater reading difficulty than controls for all tasks except puzzles (P < 0.05). The most difficult reading tasks involved puzzles, books, and finances, while the least difficult reading tasks involved notes, bills, and mail. In multivariable weighted least squares regression models of Rasch-estimated person measures of reading ability, less reading ability was found for glaucoma patients compared to controls (β = -1.60 logits, P < 0.001). Among glaucoma patients, less reading ability was associated with more severe visual field (VF) loss (β = -0.68 logits per 5-dB decrement in better-eye VF mean deviation [MD], P < 0.001) and contrast sensitivity (β = -0.76 logits per 0.1-unit lower log CS, P < 0.001). Each 5-dB decrement in the better-eye VF MD was associated with book reading on 18% fewer days (P = 0.003) and newspaper reading on 10% fewer days (P = 0.008). No statistically significant reading restriction was observed for other reading activities (P > 0.05). Glaucoma patients have less reading ability and engage less in a variety of different reading activities, particularly those requiring sustained reading. Future work should evaluate the mechanisms underlying reading disability in glaucoma to determine how patients can maintain reading ability and engagement.


Genomic Selection in Tropical Forage Grasses: Current Status and Future Applications.
The world population is expected to be larger and wealthier over the next few decades and will require more animal products, such as milk and beef. Tropical regions have great potential to meet this growing global demand, where pasturelands play a major role in supporting increased animal production. Better forage is required in consonance with improved sustainability as the planted area should not increase and larger areas cultivated with one or a few forage species should be avoided. Although, conventional tropical forage breeding has successfully released well-adapted and high-yielding cultivars over the last few decades, genetic gains from these programs have been low in view of the growing food demand worldwide. To guarantee their future impact on livestock production, breeding programs should leverage genotyping, phenotyping, and envirotyping strategies to increase genetic gains. Genomic selection (GS) and genome-wide association studies play a primary role in this process, with the advantage of increasing genetic gain due to greater selection accuracy, reduced cycle time, and increased number of individuals that can be evaluated. This strategy provides solutions to bottlenecks faced by conventional breeding methods, including long breeding cycles and difficulties to evaluate complex traits. Initial results from implementing GS in tropical forage grasses (TFGs) are promising with notable improvements over phenotypic selection alone. However, the practical impact of GS in TFG breeding programs remains unclear. The development of appropriately sized training populations is essential for the evaluation and validation of selection markers based on estimated breeding values. Large panels of single-nucleotide polymorphism markers in different tropical forage species are required for multiple application targets at a reduced cost. In this context, this review highlights the current challenges, achievements, availability, and development of genomic resources and statistical methods for the implementation of GS in TFGs. Additionally, the prediction accuracies from recent experiments and the potential to harness diversity from genebanks are discussed. Although, GS in TFGs is still incipient, the advances in genomic tools and statistical models will speed up its implementation in the foreseeable future. All TFG breeding programs should be prepared for these changes.


Ear, nose and throat and respiratory manifestations of gastro-esophageal reflux disease: an increasing conundrum.
Although recent studies suggest that gastro-oesophageal reflux disease (GORD) may contribute frequently to ear, nose and throat (ENT) and respiratory diseases, the cause-and-effect relationship is far from proven. This article addresses this controversial topic, emphasising recent literature that raises concerns about the credibility of this association and our tests to make this diagnosis. The author believes that these extra-oesophageal symptoms suspected to be secondary to GORD are a conundrum, but selective use of aggressive proton-pump-inhibitor therapeutic trials may help to resolve this issue in our patients.


Sexual arousal in women with provoked vestibulodynia: the application of laser Doppler imaging to sexual pain.
Introduction. Women with provoked vestibulodynia (PVD) report lower sexual arousal than nonaffected women, however, laboratory studies of arousal have reported contradictory results about whether group differences exist in genital and subjective arousal. Aim. To examine genital and subjective sexual arousal in women with and without PVD. Methods. Eligible women with and without PVD (N = 42) attended a laboratory session that included an interview, questionnaire completion, and genital imaging. A direct measure of superficial blood flow-laser Doppler imaging-was used to assess vulvar blood flow levels while participants watched three films, including an erotic film. Participants answered questions about their level of sexual arousal before, during, and after the erotic film. Main Outcome Measures. Average vulvar blood flow levels during the baseline and erotic films, numerical ratings of subjective sexual arousal and anxiety, as well as questionnaire measures of arousal. Results. There was a significant group difference in genital arousal, whereby the PVD group showed a lower genital response to the erotic film, as well as a significant interaction between baseline blood flow and group membership. Separate group regression analyses demonstrated that baseline blood flow explained a substantial amount of the variance in erotic film blood flow in the control group (70%), while only 27% was explained by this variable in the PVD group. There were no differences in subjective sexual arousal or anxiety between the groups. Across questionnaire measures, women with PVD reported lower sexual arousal than the control group. Conclusions. The results suggest that women with PVD show lower genital responsiveness than nonaffected women to sexual stimuli in a laboratory setting and that their genital arousal is likely impacted by a number of biopsychosocial factors. Boyer SC, Pukall CF, and Chamberlain SM. Sexual arousal in women with provoked vestibulodynia: The application of laser Doppler imaging to sexual pain. J Sex Med **;**:**-**.


Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs.
In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the decapping enzyme Dcp1p, the 5'-to-3' exoribonuclease Xrn1p, and the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p. To identify specific functions for the NMD factors, we analyzed the mRNA decay phenotypes of yeast strains containing deletions of DCP1 or XRN1 and UPF1, NMD2, or UPF3. Our results indicate that Upf1p, Nmd2p, and Upf3p regulate decapping and exonucleolytic degradation of nonsense-containing mRNAs. In addition, we show that these factors also regulate the same processes in the degradation of wild-type mRNAs. The participation of the NMD factors in general mRNA degradation suggests that they may regulate an aspect of translation termination common to all transcripts.


Pediatric myasthenia gravis with a combination of AChR and RyR is associated with an earlier onset and lower CSR rate: A cohort study in southwest China.
The clinical manifestations and prognosis of myasthenia gravis are related to antibodies, and children are affected differently than adults. The presence of ryanodine receptor and titin antibodies in adults indicates late onset and severe disease related to thymoma, but their role in children is rarely reported. This study collected a cohort of children according to inclusion and exclusion criteria, consisting of antibody-negative, AChR-positive, and AChR with or without titin and RyR antibodies. The differences among groups in general conditions, clinical manifestation, treatment and prognosis were compared. In total, 171 patients were included: 33 patients (19.30%) were antibody-negative, 84 patients (49.12%) were positve for AChR antibody, 22 patients (12.87%) were positve for AChR and RyR antibodies, 5 patients (2.92%) were positve for AChR and Titin antibodies, and 27 patients (15.79%) were positve for AChR, RyR and Titin antibodies. The median onset age of all the patients was 57.8 (9-177) months, and patients with AChR and RyR antibodies (p = 0.02) and AChR, RyR and Titin antibodies (p = 0.0006) had a younger onset age than patients with AChR antibodies. The rate of generalized MG and MG-ADL before treatment in the AChR-, RyR- and Titin antibody-positive groups was distinctly higher than that in the AChR antibody-positive group (p = 0.038, p = 0.0325). The rate of IVIG use in the AChR-, RyR- and Titin antibody-positive groups (p = 0.0388) was higher than that in the AChR antibody-positive group. The rate of immunosuppressant use in the AChR and RyR antibody-positive group (p = 0.0415) and in the AChR, RyR and Titin antibody-positive group (p = 0.0006) was higher than that in the AChR antibody-positive group. Plasmapheresis was performed in 1 case in the AChR-, RyR- and Titin antibody-positive groups. The CSR rate in the AChR and RyR antibody-positive group (p = 0.0423) and in the AChR, RyR and Titin antibody-positive group (p = 0.0152) was significantly lower than that in the AChR antibody-positive group. Gender, ptosis severity, and CSR time were not significantly different between groups. We summarized one of the largest cohorts of pediatric MG patients and compared the clinical phenotype of patients with antibody-negative, AChR-positive, and AChR with or without titin and RyR antibodies. The results showed that patients with AChR and RyR antibodies had a younger onset age, a higher immunosuppressant use rate and a lower CSR rate.


The role of the neonatal intensive care nurse in decision-making: advocacy, involvement in ethical decisions and communication.
Neonatal intensive care unit (NICU) nurses are often faced with complex clinical and ethical problems. Little is known about the role of the NICU nurse in ethical decision-making, or processes that inform decision-making in this setting. The purpose of this study was to explore and describe nurses' perceptions of their role as patient advocate, clinical situations that cause them concern and the extent of their involvement in ethical decision-making. A combined quantitative and qualitative research design was used. A questionnaire was administered to nurses working in the NICU of the sole perinatal tertiary referral centre of Western Australia, Australia. Findings showed that NICU nurses saw their role in ethical decision-making primarily as advocating for the best interests of the infant and family, that they used clinical knowledge and experience to guide ethical decision-making, they were able to clearly articulate ethical problems and respond to them according to the clinical scenario and, while being primarily assertive in presenting their views, some nurses took a more passive approach. These findings support the need for development of a multidisciplinary model for ethical decision-making, where the view of all team members are considered.


Emerging roles of angiopoietin-like 4 in human cancer.
Angiopoietin-like 4 (ANGPTL4) is best known for its role as an adipokine involved in the regulation of lipid and glucose metabolism. The characterization of ANGPTL4 as an adipokine is largely due to our limited understanding of the interaction partners of ANGPTL4 and how ANGPTL4 initiates intracellular signaling. Recent findings have revealed a critical role for ANGPTL4 in cancer growth and progression, anoikis resistance, altered redox regulation, angiogenesis, and metastasis. Emerging evidence suggests that ANGPTL4 function may be drastically altered depending on the proteolytic processing and posttranslational modifications of ANGPTL4, which may clarify several conflicting roles of ANGPTL4 in different cancers. Although the N-terminal coiled-coil region of ANGPTL4 has been largely responsible for the endocrine regulatory role in lipid metabolism, insulin sensitivity, and glucose homeostasis, it has now emerged that the COOH-terminal fibrinogen-like domain of ANGPTL4 may be a key regulator in the multifaceted signaling during cancer development. New insights into the mechanistic action of this functional domain have opened a new chapter into the possible clinical application of ANGPTL4 as a promising candidate for clinical intervention in the fight against cancer. This review summarizes our current understanding of ANGPTL4 in cancer and highlights areas that warrant further investigation. A better understanding of the underlying cellular and molecular mechanisms of ANGPTL4 will reveal novel insights into other aspects of tumorigenesis and the potential therapeutic value of ANGPTL4.


[Effect of vitamin D3 on the formation of proteoglycans and tissue calcification].
Nonspecific calcinosis engendered by vitamin D3 is associated with extraosseous calcium deposits, in connection with which proteoglycans (PG) can be observed. After administration of vitamin D3 tissue samples from cardiac muscle and aorta of rats were taken and traced ultrahistochemically by means of the acriflavin-phosphotungstic acid contrast-method. The calcification began first with an increase in PG in the cell membranes of the sarcolemma, in the ground substance, and in the capillaries of the interstice. Subsequently circularly formed concentric layers of calcium encrustations appear in the above-mentioned locations. Large amounts of PG were also observed prior to the formation of crystalline fascicular calcium deposits in the ground substance and in the elastic fibers of the media of the aorta. This process began at the outer edges of the media and continued towards their interior, resulting in a loosening of the bond between the elastic fibers and the sarcoplasmic continuations of the smooth muscle cells. The extraosseous calcification resulting after the administration of vitamin D3 can therefore be considered not only as a result of hypercalcemia, but also as a result of stimulation of the production of ground substance through vitamin D3. This form of calcification represents a characteristic pathophysiological process which is differentiated from the dystrophic form in that it begins without previous cell damage.


Traps and attractants for wood-boring insects in ponderosa pine stands in the Black Hills, South Dakota.
Recent large-scale wildfires have increased populations of wood-boring insects in the Black Hills of South Dakota. Because little is known about possible impacts of wood-boring insects in the Black Hills, land managers are interested in developing monitoring techniques such as flight trapping with semiochemical baits. Two trap designs and four semiochemical attractants were tested in a recently burned ponderosa pine, Pinus ponderosa Dougl. ex Laws., forest in the Black Hills. Modified panel and funnel traps were tested in combination with the attractants, which included a woodborer standard (ethanol and alpha-pinene), standard plus 3-carene, standard plus ipsenol, and standard plus ipsdienol. We found that funnel traps were equally efficient or more efficient in capturing wood-boring insects than modified panel traps. Trap catches of cerambycids increased when we added the Ips spp. pheromone components (ipsenol or ipsdienol) or the host monoterpene (3-carene) to the woodborer standard. During the summers of 2003 and 2004, 18 cerambycid, 14 buprestid, and five siricid species were collected. One species of cerambycid, Monochamus clamator (LeConte), composed 49 and 40% of the 2003 and 2004 trap catches, respectively. Two other cerambycids, Acanthocinus obliquus (LeConte) and Acmaeops proteus (Kirby), also were frequently collected. Flight trap data indicated that some species were present throughout the summer, whereas others were caught only at the beginning or end of the summer.


Empiric Piperacillin-Tazobactam versus Carbapenems in the Treatment of Bacteraemia Due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae.
Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a common cause of bacteraemia in endemic countries and may be associated with high mortality; carbapenems are considered the drug of choice. Limited data suggest piperacillin-tazobactam could be equally effective. We aimed to compare 30-day mortality of patients treated empirically with piperacillin-tazobactam versus a carbapenem in a multi-centre retrospective cohort study in Singapore. Only patients with active empiric monotherapy with piperacillin-tazobactam or a carbapenem were included. A propensity score for empiric carbapenem therapy was derived and an adjusted multivariate analysis of mortality was conducted. A total of 394 patients had ESBL-Escherichia.coli and ESBL-Klebsiella pneumoniae bacteraemia of which 23.1% were community acquired cases. One hundred and fifty-one received initial active monotherapy comprising piperacillin-tazobactam (n = 94) or a carbapenem (n = 57). Patients who received carbapenems were less likely to have health-care associated risk factors and have an unknown source of bacteraemia, but were more likely to have a urinary source. Thirty-day mortality was comparable between those who received empiric piperacillin-tazobactam and a carbapenem (29 [30.9%] vs. 17 [29.8%]), P = 0.89). Those who received empiric piperacillin-tazobactam had a lower 30-day acquisition of multi-drug resistant and fungal infections (7 [7.4%] vs. 14 [24.6%]), P<0.01). After adjusting for confounders, use of empiric piperacillin-tazobactam was not associated with increased 30-day mortality (OR 1.00, 95% CI; 0.45-2.17). Empiric piperacillin-tazobactam was not associated with increased 30-day mortality and may result in fewer multi-drug resistant and fungal infections when compared with a carbapenem.


Adoptive immunotherapy for cancer or viruses.
Adoptive immunotherapy, or the infusion of lymphocytes, is a promising approach for the treatment of cancer and certain chronic viral infections. The application of the principles of synthetic biology to enhance T cell function has resulted in substantial increases in clinical efficacy. The primary challenge to the field is to identify tumor-specific targets to avoid off-tumor, on-target toxicity. Given recent advances in efficacy in numerous pilot trials, the next steps in clinical development will require multicenter trials to establish adoptive immunotherapy as a mainstream technology.


Surgical treatment and the patient with cystic fibrosis.
It has long been recognized that the patient with chronic lung disease, malnutrition, vitamin K deficiency or electrolyte and blood gas disturbances presents a special problem for the surgeon. Patients with cystic fibrosis have all of these abnormalities. Until recently, the patient with cystic fibrosis was exclusively the domain of the pediatrician. Today, with the increasing number of patients over the age of 20 years, internists and surgeons have an increasingly important role in the care of these patients. In addition, since women with cystic fibrosis are capable of bearing children, the need for genetic, obstetric and gynecologic counseling is becoming more apparent. Although the patient with cystic fibrosis is generally at a much greater risk for the complications of surgical treatment than the normal patient, experience in the management of these patients has greatly improved the outlook. However, in most instances, surgical management of the patient with cystic fibrosis represents palliation, since these patients usually die of the medical complications of their disease. Further controlled studies are needed to fully evaluate the role of surgical treatment in the sequelas of cystic fibrosis.


U.S. Female Veterans Who Do and Do Not Rely on VA Health Care: Needs and Barriers to Mental Health Treatment.
To determine mental health service utilization and barriers among female veterans, this study examined the prevalence of U.S. female veterans who identified the U.S. Department of Veterans Affairs (VA) as their main source of health care. This observational study used data from a nationally representative sample of 1,202 veterans who completed a Web-based survey. The analysis compared sociodemographic and clinical characteristics, mental health service use, and perceived barriers to mental health care among female veterans who do and do not use the VA as their main source of health care and male veterans who mainly use VA health care. By gender, 23.4% of female veterans and 19.6% of male veterans identified the VA as their main source of health care, which was not significantly different. Compared with male VA patients, women were more likely to be single, younger, and from a racial-ethnic minority group and to screen positive for depression and posttraumatic stress disorder (PTSD), but they were less likely to have a substance use disorder. Compared with female veterans who did not mainly use VA care, female VA patients were more likely to be on a low income, not employed, from racial-ethnic minority groups, and combat veterans, and they were more likely to have a disability, to screen positive for PTSD, and to report poorer mental health-related functioning. There were no group differences in mental health service use, and the most frequently endorsed barriers to using mental health care across veteran groups were "high treatment costs" and "being seen as weak." These findings highlight the health care needs of female VA service users and support efforts to dispel misconceptions and stigma related to mental health care.


How Dissociation of Carboxylic Acid Groups in a Weak Polyelectrolyte Brush Depend on Their Distance from the Substrate.
A weak polyelectrolyte brush is composed of a layer of polyacids or polybases grafted by one end of their chains to a substrate surface. For such brush layers immersed in an aqueous solution, the dissociation behavior of the acidic or basic groups and the structural and physical properties of the brush layer will thus be strongly dependent on the environmental conditions. For a polyacid brush layer consisting of, e.g., poly(acrylic acid), this means that the chains in the brush layer will be charged at high pH and uncharged at low pH. However, theoretical scaling laws not only foresee the structural changes occurring in response to the pH-induced dissociation behavior but also how the dissociation behavior of the brush layer depends on the ionic strength of the aqueous solution and the density of acidic groups within the brush layer. We have herein employed spectroscopic ellipsometry and a quartz crystal microbalance with dissipation monitoring (QCM-D) to experimentally evaluate the theoretically predicted dissociation and structural behavior of PAA brushes. Spectroscopic ellipsometry allows us to study the brush thickness as a function of pH and ionic strength, while QCM-D gives us an opportunity to investigate the swelling behavior of PAA brushes at various penetration depths of propagating acoustic waves. Our studies show that the dissociation degree of the carboxylic acid groups in a PAA brush increases with increasing distance from the substrate. Moreover, the ionic strength enhances carboxylic acid dissociation, such that a higher ionic strength leads to a narrower distribution and higher average dissociation degree. In conclusion, our results provide an experimental verification of the theoretically predicted gradient in the degree of dissociation of the acid groups in weak polyacid brush layers and shows that at a pH value equal to approximately the average pKa value of the brush, the state of the acid groups varies from being almost uncharged to almost fully dissociated depending on the ionic strength and vertical position in the brush.


Epidermal growth factor regulates fatty acid uptake and metabolism in Caco-2 cells.
Epidermal growth factor (EGF) has been reported to stimulate carbohydrate, amino acid, and electrolyte transport in the small intestine, but its effects on lipid transport are poorly documented. This study aimed to investigate EGF effects on fatty acid uptake and esterification in a human enterocyte cell line (Caco-2). EGF inhibited cell uptake of [14C]palmitate and markedly reduced its incorporation into triglycerides. In contrast, the incorporation in phospholipids was enhanced. To elucidate the mechanisms involved, key steps of lipid synthesis were investigated. The amount of intestinal fatty acid-binding protein (I-FABP), which is thought to be important for fatty acid absorption, and the activity of diacylglycerol acyltransferase (DGAT), an enzyme at the branch point of diacylglycerol utilization, were reduced. EGF effects on DGAT and on palmitate esterification occurred at 2-10 ng/ml, whereas effects on I-FABP and palmitate uptake occurred only at 10 ng/ml. This suggests that EGF inhibited palmitate uptake by reducing the I-FABP level and shifted its utilization from triglycerides to phospholipids by inhibiting DGAT. This increase in phospholipid synthesis might play a role in the restoration of enterocyte absorption function after intestinal mucosa injury.


Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.
The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56). Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).


Ectopically expressed Slc34a2a sense-antisense transcripts cause a cerebellar phenotype in zebrafish embryos depending on RNA complementarity and Dicer.
Natural antisense transcripts (NATs) are complementary to protein coding genes and potentially regulate their expression. Despite widespread occurrence of NATs in the genomes of higher eukaryotes, their biological role and mechanism of action is poorly understood. Zebrafish embryos offer a unique model system to study sense-antisense transcript interplay at whole organism level. Here, we investigate putative antisense transcript-mediated mechanisms by ectopically co-expressing the complementary transcripts during early zebrafish development. In zebrafish the gene Slc34a2a (Na-phosphate transporter) is bi-directionally transcribed, the NAT predominantly during early development up to 48 hours after fertilization. Declining levels of the NAT, Slc34a2a(as), coincide with an increase of the sense transcript. At that time, sense and antisense transcripts co-localize in the endoderm at near equal amounts. Ectopic expression of the sense transcript during embryogenesis leads to specific failure to develop a cerebellum. The defect is RNA-mediated and dependent on sense-antisense complementarity. Overexpression of a Slc34a2a paralogue (Slc34a2b) or the NAT itself had no phenotypic consequences. Knockdown of Dicer rescued the brain defect suggesting that RNA interference is required to mediate the phenotype. Our results corroborate previous reports of Slc34a2a-related endo-siRNAs in two days old zebrafish embryos and emphasize the importance of coordinated expression of sense-antisense transcripts. Our findings suggest that RNAi is involved in gene regulation by certain natural antisense RNAs.


The Milwaukee Youth Belongingness Scale (MYBS): Development and validation of the scale utilizing item response theory.
The examination of belonging in schools, connecting school belonging to a plethora of academic and psychosocial outcomes, has been well established in the literature. Researchers have measured school belonging most frequently with the Psychological Sense of School Membership, but its psychometric properties have been called into question by several researchers. Further, the scale measures 1 subset of belonging (i.e., school), leaving out powerful belonging connections in other areas of a student's life, namely peers and family. The current study examines the development and validation of the Milwaukee Youth Belongingness Scale. This process was examined by utilizing item response theory and a secondary analysis confirming the factor structure and the validation of the scale by comparing it to other constructs. The results confirm a 9-item scale that involves a total scale score and 3 factors (School, Peers, Family). Implications for mental health professionals and future research are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


FAM190A rearrangements provide a multitude of individualized tumor signatures and neo-antigens in cancer.
We found FAM190A transcripts to have internal rearrangements in 40% (19/48) of unselected human cancers. Most of these tumors (84%) had in-frame structures, 94% of which involved deletion of exon 9. The FAM190A gene is located at 4q22.1 in a region of common fragility, FRA4F. Although normally stable in somatic cells, common fragile sites can be hotspots of rearrangement in cancer. The genomic deletion patterns observed at some sites, including FRA4F at 4q22.1, are proposed to be the result of selection for disrupted tumor-suppressor genes. Our evidence, however, indicated additional patterns for FAM190A. We found genomic deletions accounted for some FAM190A in-frame structures, and cases pre-selected for FAM190A genomic deletions had a yet higher prevalence of FAM190A rearrangements. Our evidence of widespread in-frame heterozygous and homozygous rearrangements affecting this gene in tumors of multiple types leads speculation on structural grounds that the mutant forms may retain, provide new, or possibly convey dominant-negative functions. Although a functionally uncharacterized gene, it is evolutionary conserved across vertebrates. In addition to its potential oncogenic role, the in-frame deletions predict the formation of cancer-specific FAM190A peptide sequences (neo-antigens) with potential diagnostic and therapeutic usefulness.


ReaxFF molecular dynamics simulations of electrolyte-water systems at supercritical temperature.
We have performed ReaxFF molecular dynamics simulations of alkali metal-chlorine pairs in different water densities at supercritical temperature (700 K) to elucidate the structural and dynamical properties of the system. The radial distribution function and the angular distribution function explain the inter-ionic structural and orientational arrangements of atoms during the simulation. The coordination number of water molecules in the solvation shell of ions increases with an increase in the radius of ions. We find that the self-diffusion coefficient of metal ions increases with a decrease in density under supercritical conditions due to the formation of voids within the system. The hydrogen bond dynamics has been interpreted by the residence time distribution of various ions, which shows Li+ having the highest water retaining capability. The void distribution within the system has been analyzed by using the Voronoi polyhedra algorithm providing an estimation of void formation within the system at high temperatures. We observe the formation of salt clusters of Na+ and K+ at low densities due to the loss of dielectric constants of ions. The diffusion of ions gets altered dramatically due to the formation of voids and nucleation of ions in the system.


Laser scanning cytometry (LCS) allows detailed analysis of the cell cycle in PI stained human fibroblasts (TIG-7).
We have demonstrated a method for the in situ determination of the cell cycle phases of TIG-7 fibroblasts using a laser scanning cytometer (LSC) which has not only a function equivalent to flow cytometry (FCM) but also has a capability unique in itself. LSC allows a more detailed analysis of the cell cycle in cells stained with propidium iodide (PI) than FCM. With LSC it is possible to discriminate between mitotic cells and G2 cells, between post-mitotic cells and G1 cells, and between quiescent cells and cycling cells in a PI fluorescence peak (chromatin condensation) vs. fluorescence value (DNA content) cytogram for cells stained with PI. These were amply confirmed by experiments using colcemid and adriamycin. We were able to identify at least six cell subpopulations for PI stained cells using LSC; namely G1, S, G2, M, postmitotic and quiescent cell populations. LSC analysis facilitates the monitoring of effects of drugs on the cell cycle.


Imaging diagnosis--computed tomographic, surgical, and histopathologic characteristics of an infiltrative angiolipoma in a dog.
A 6-year-old female spayed Shetland Sheepdog presented for evaluation of a subcutaneous mass over the right prescapular region. The mass had been cytologically diagnosed as a lipoma by the referring veterinarian 20 months prior, but had grown significantly and was very firm. CT scan of the mass was suggestive of neoplasia; however, the tissue of origin could not be determined. Histopathologic evaluation diagnosed infiltrative angiolipoma, and marginal resection of the tumor was performed. Infiltrative angiolipomas are benign but locally aggressive neoplasms uncommonly reported in veterinary medicine. This report correlates the clinical, CT, and histopathologic characteristics of an infiltrative angiolipoma.


Sphenopalatine Ganglion Nerve Block for the Treatment of Migraine Headaches in the Pediatric Population.
Persistent headaches and migraines are common in pediatrics with various treatment options. The sphenopalatine ganglion (SPG) has been identified as communicating with the parasympathetic autonomic nervous system and pain receptors. In adults, SPG block is an established treatment but there is no published literature in pediatrics. The purpose of this study is to analyze the SPG block in pediatrics. Retrospective, single-center study. This study was conducted at Phoenix Children's Hospital in Phoenix, Arizona. A comprehensive review of patient charts from 2015-2018 of all pediatric SPG blockades performed by interventional radiology were included in the analysis. Utilizing fluoroscopic guidance, a SphenoCath was inserted into each nostril and after confirming position, and 4% lidocaine injected. Pre- and postprocedural pain was assessed using the Visual Analog Scale (VAS). Immediate and acute complications were documented. A total of 489 SPG blocks were performed in patients between ages 6 and 26 years who were diagnosed with migraine or status migrainosus. One hundred percent technical success was achieved with mean reduction of pain scores of 2.4, which was statistically significant (P < 0.0001). There were no immediate or acute complications. Results of this study were based on retrospective study. The use of VAS may be subjective, and the need of a prospective study may be necessary. With 100% technical success, statistically significant pain reduction, and no complications, we support SPG block in the pediatric population as a simple, efficacious, and safe treatment option for refractory headaches. It is routinely performed in less than 10 minutes and commonly negates the need for inpatient headache pain management. Given its minimal invasivity, we support the use of SPG blockade as a therapeutic treatment in refractory pediatric migraines as it reduces the need for intravenous medications, prolonged pain control, or hospital admission.


Encoding nondeterministic fuzzy tree automata into recursive neural networks.
Fuzzy neural systems have been a subject of great interest in the last few years, due to their abilities to facilitate the exchange of information between symbolic and subsymbolic domains. However, the models in the literature are not able to deal with structured organization of information, that is typically required by symbolic processing. In many application domains, the patterns are not only structured, but a fuzziness degree is attached to each subsymbolic pattern primitive. The purpose of this paper is to show how recursive neural networks, properly conceived for dealing with structured information, can represent nondeterministic fuzzy frontier-to-root tree automata. Whereas available prior knowledge expressed in terms of fuzzy state transition rules are injected into a recursive network, unknown rules are supposed to be filled in by data-driven learning. We also prove the stability of the encoding algorithm, extending previous results on the injection of fuzzy finite-state dynamics in high-order recurrent networks.


Characterization of trypanosome isolates from naturally infected horses on a farm in Kenya.
Following an outbreak of trypanosomosis in horses on a farm in Kenya, 18 trypanosome isolates were collected from the infected animals over a period of one and a half years and cryopreserved for characterization. The characterization was done on the basis of morphology using Giemsa-stained blood and buffy coat smears, infectivity to mice, recombinant DNA hybridization, and chromosome separation by orthogonal field alternation gel electrophoresis (OFAGE). Morphologically, all the trypanosome isolates were identified as belonging to the subgenus Nannomonas, and a total of 16 out of the 18 isolates grew in mice. Using the recombinant DNA hybridization technique, the isolates were further classified as the 'savannah' type of Trypanosoma congolense. Furthermore, chromosome separation by OFAGE, carried out on six clones derived from different isolates, exhibited a profile characteristic of T. congolense, 'savannah' type. However, there were differences in the number and positions of the medium-sized and minichromosomes indicating a diversity of serodemes within the isolates. Hence the infecting trypanosomes in this disease outbreak were T. congolense, 'savannah' type, and comprised several serodemes or strains.


A Large Database Analysis of Rates of Aneurysm Screening, Elective Treatment, and Subarachnoid Hemorrhage in Patients With Polycystic Kidney Disease.
Professional societies provide conflicting guidelines on aneurysm screening in patients with polycystic kidney disease (PKD), and the rate of subarachnoid hemorrhage (SAH) is poorly understood. To evaluate screening, elective treatment, and the rate of SAH in patients with known PKD. We examined longitudinally linked claims data from a large private insurer, identifying screening, elective treatment, aneurysmal subarachnoid hemorrhage (aSAH) and secured aneurysmal SAH (saSAH) in 2004 to 2014 amongst patients with known PKD. We identified 20 704 patients diagnosed with PKD. Among patients with an initial PKD diagnosis, 51/446 (15.9%) underwent angiographic screening within 2 yr. Forty aneurysms were treated electively in 48 868 yr at risk in PKD patients (82/100K patient yr, 95% confidence interval [CI] 60-112) vs 24 elective treatments in 349 861 yr at risk in age- and sex-matched controls (7/100K patient yr, 95% CI 5-10, P < .0001). Eleven admissions for aSAH were identified in PKD patients (23/100K patient yr, 95% CI 13-41) and 22 admissions for aSAH in controls (6/100K patient yr, 95% CI 4-10), giving an incidence rate ratio (IRR) of 3.6 (95% CI 1.7-7.4, P < .0001) and a comorbidity-adjusted IRR of 3.1 (95% CI 1.4-6.9). The incidence of saSAH was proportionally even higher in PKD patients than controls, 16 vs 2/100K patient years, IRR 9.5 (95% CI 3.3-27.5, P < .0001). Screening in PKD is performed only selectively, though resulting rates of elective treatment were over 10× those of controls. Despite screening and treatment, the rate of SAH remains significantly elevated over that of controls.


A visible light photoelectrochemical biosensor coupling enzyme-inhibition for organophosphates monitoring based on a dual-functional Cd(0.5)Zn(0.5)S-reduced graphene oxide nanocomposite.
A novel visible light photoelectrochemical (PEC) platform coupled with enzyme-inhibition for rapid and sensitive determination of organophosphates (OPs) was constructed based on a dual-functional Cd0.5Zn0.5S-reduced graphene oxide (Cd0.5Zn0.5S-rGO) nanocomposite. Due to the inherent biocompatibility of the Cd0.5Zn0.5S-rGO nanocomposite, acetylcholinesterase (AChE) immobilized on the Cd0.5Zn0.5S-rGO modified electrode can hydrolyze acetylthiocholine chloride into thiocholine, which could increase the photocurrent of the enzyme electrode, and the further inhibition of OPs on the enzyme electrode could decrease the photocurrent response. Based on the notable change in the PEC response of the AChE-Cd0.5Zn0.5S-rGO modified electrode and using Dursban as a model, a simple and effective way for PEC monitoring of OPs is proposed, which showed a wide linear range of 0.001-1 μg mL(-1) with a low detection limit of 0.3 ng mL(-1) (S/N = 3). Moreover, the biosensor was successfully challenged with water samples, demonstrating a new method for rapid and sensitive screening/evaluating exposure to organophosphorus pesticides and other hazardous substances.


Representation of Women on Journal Editorial Boards Affiliated with the Association of American Medical College's Council of Faculty and Academic Societies.
Background: The Council of Faculty and Academic Societies (CFAS) comprises representatives from medical schools and professional societies who guide the Association of American Medical Colleges (AAMC). Given the AAMC's stated mission to improve diversity and inclusion, we used gender-related representation on journal editorial boards as a proxy for evaluating CFAS member societies' commitments to equity. Methods: From screenshots of journal mastheads (n = 44) collected June 3-6, 2019, individuals were categorized by editorial position. Outcome measures included numbers of men and women among faculty, deans, department chairs, physicians, and nonphysicians on editorial boards. Outcomes were compared with 2018 AAMC and US Bureau of Labor Statistics workforce data. Results: Overall, the proportion of women among journal editors was 29.0% (364 of 1,255), range 0%-53.3%. This proportion was significantly less than the proportion of women among US medical school faculty and medical scientists. The lowest percentages of women were found among journals' section or topic editors (19.2%) and editors-in-chief (20.4%). Men were significantly more likely to be a professor or department chair and women were significantly more likely to be an associate professor or assistant professor, suggesting a bidirectional process between rank and editorial position that may inhibit the advancement of academic women, particularly women physicians. Conclusions: This study revealed disparities in the equitable representation of women among CFAS member-affiliated journal editors. Because CFAS member societies participate in a mutually beneficial relationship with the AAMC, they should strive to attain the equity goals set forth by the AAMC.


The heart reinnervates after transplantation.
Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown. Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg), and tyramine (1.2 microg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically. Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal beta-adrenergic receptor affinity and density but reduced catecholamine and alpha-tubulin contents. The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular beta-adrenergic receptor function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.


The effect of periprosthetic bone loss on the failure risk of tibial total knee arthroplasty.
The effect of long-term periprosthetic bone loss on the process of aseptic loosening of tibial total knee arthroplasty (TKA) is subject to debate. Contradicting studies can be found in literature, reporting either bone resorption or bone formation before failure of the tibial tray. The aim of the current study was to investigate the effects of bone resorption on failure of tibial TKA, by simulating clinical postoperative bone density changes in finite element analysis (FEA) models and FEA models were created of two tibiae representing cases with good and poor initial bone quality which were subjected to a walking configuration and subsequently to a traumatic stumbling load. Bone failure was simulated using a crushable foam model incorporating progressive yielding. Repetitive loading under a level walking load did not result in failure of the periprosthetic bone in neither the good nor poor bone quality tibia at the baseline bone densities. When applying a stumble load, a collapse of the tibial reconstruction was noticed in the poor bone quality model. Incorporating postoperative bone loss led to a significant increase of the failure risk, particularly for the poor bone quality model in which subsidence of the tibial component was substantial. Our results suggest bone loss can lead to an increased risk of a collapse of the tibial component, particularly in case of poor bone quality at the time of surgery. The study also examined the probability of medial or lateral subsidence of the implant and aimed to improve clinical implications. The FEA model simulated plastic deformation of the bone and implant subsidence, with further validation required via mechanical experiments.


Antiplatelet therapy in aneurysmal subarachnoid hemorrhage: a systematic review.
Observational studies suggest that platelet inhibitors reduce the risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage and thereby have a beneficial effect on clinical outcome. Robust evidence, however, is lacking. We performed a systematic meta-analysis to determine whether antiplatelet therapy has a beneficial effect after SAH. We searched Medline and the Cochrane Library to identify all randomized controlled trials of antiplatelet drugs versus control and calculated relative risks with corresponding 95% confidence intervals (CIs) for poor outcome (dependence or death), the occurrence of DCI, and the occurrence of any intracranial hemorrhage. We included 5 trials totaling 699 patients. The overall relative risk for poor outcome was 0.87 (95% CI, 0.65 to 1.17); for the occurrence of DCI (reported in 3 of the 5 studies), 0.65 (95% CI, 0.47 to 0.89); and for the occurrence of intracranial hemorrhage, 1.19 (reported in 4 of the 5 studies) (95% CI, 0.76 to 1.85). Our data indicate that antiplatelet drugs reduce the risk of DCI in patients with subarachnoid hemorrhage. A randomized clinical trial is warranted to assess the effect on overall outcome.


Treatment of a Class II Division 1 malocclusion with the combination of a myofunctional trainer and fixed appliances.
This case report describes the combined use of a myofunctional Trainer for Braces and fixed appliances to treat a 10-year-old girl with a Class II Division 1 malocclusion that featured severe maxillary incisor protrusion, a large overjet, and a V-shaped maxillary arch. She had a convex profile with an underdeveloped mandible. The superiority of myofunctional training in the case was to eliminate mouth breathing and lip sucking habits, train the oral musculature, stimulate mandibular growth, and make braces work more efficiently. The posttreatment facial photographs show improvement in the facial profile. Proper occlusion and facial balance were created, which were quite stable as demonstrated by the patient's 4-year follow-up records.


Differential regulation by Toll-like receptor agonists reveals that MCPIP1 is the potent regulator of innate immunity in bacterial and viral infections.
Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an important immune regulator involved in macrophage activation, modulation of its expression by all known TLR agonists has never been documented. In this study, we present for the first time that in human monocyte-derived macrophages all TLR agonists, except CpG, markedly induced the expression of MCPIP1. The level of the induced transcript, as well as the protein and time of their appearance varied depending on the agonist. Furthermore, we confirmed the strong and differential upregulation of MCPIP1 during bacteria, virus and fungus infection. MCPIP1 belongs to a group of early-response genes; however, in the present study, we show for the first time the sustained high level of MCPIP1 expression during long-term Staphylococcus aureus infection. Taken together, our results implicate MCPIP1 as a potent regulator of innate immunity, which can be strongly engaged in the pathogenesis of acute and chronic infective diseases.


Biocidal properties of maltose reduced silver nanoparticles against American foulbrood diseases pathogens.
Bee disease caused by spore-forming Paenibacillus larvae and Paenibacillus alvei is a serious problem for honey production. Thus, there is an ongoing effort to find an effective agent that shows broad biocidal activity with minimal environmental hazard. In this study, the biocidal effect of maltose reduced silver nanoparticles (AgNPs) is evaluated against American foulbrood and European foulbrood pathogens. The results demonstrate that the maltose reduced AgNPs are excellent short and long-term biocides against P. larvae isolates. The long-term effect suggests that the Ag+ ions are released from the AgNPs with increasing time in a controlled manner.


Genes 46 and 47 of phage T4: possible compensation for loss of their function.
The gene 46 and 47 functions of phage T4 are required for normal DNA replication, recombination, u.v. repair and host DNA breakdown, and yet am mutants defective in these genes characteristically form tiny plaques on Escherichia coli strains lacking an am suppressor. Our results imply that this limited growth is not due to misreading of am codons or partial function of nearly complete poly-peptides terminated at the am mutation. Thus it appears that genes 46 and 47 are not entirely essential, perhaps because other phage or host products can partially compensate for their loss.


Expression changes in mRNAs and mitochondrial damage in lens epithelial cells with selenite.
An overdose of sodium selenite induces cataracts in young rats. The mid-stage events producing the cataract include calpain-induced hydrolysis and precipitation of lens proteins. Apoptosis in lens epithelial cells has been suggested as an initial event in selenite cataracts. Expression levels of two genes associated with apoptosis were altered in lens epithelial cells from selenite-injected rats. The purpose of the present experiment was to perform a more comprehensive search for changes in expression of mRNAs in lens epithelial cells in order to more fully delineate the early events in selenite-induced cataracts. Lens epithelial cells were harvested at 1 and 2 days after a single subcutaneous injection of sodium selenite (30 mumol/kg body weight) into 12-day-old rats. Gene expression was analyzed using a commercial DNA array (Rat Genome U34A GeneChip array, Affymetrix). Of approximately 8000 genes assayed by hybridization, 13 genes were decreased and 27 genes were increased in the rat lens epithelial cells after injection of selenite. Some of the up-regulated genes included apoptosis-related genes, and a majority of the down-regulated genes were mitochondrial genes. Previously observed changes in expression of EGR-1 mRNA were also confirmed. Changes in the expression patterns of mRNAs were also confirmed by RT-PCR. To determine the mechanism for damage of lens epithelial cells (alpha TN4 cell) by culture in selenite, leakage of cytochrome c from mitochondria was measured. Selenite caused significant leakage of cytochrome c into the cytosol of alpha TN4 cells. Our data suggested that the loss of integrity of lens epithelial cells by selenite might be caused by preferential down-regulation of mitochondrial RNAs, release of cytochrome c, and impaired mitochondrial function. Up-regulation of mRNAs involved in maintenance of DNA, regulation of metabolism, and induction of apoptosis may also play roles.


Gastrointestinal Complications Following Radical Cystectomy Using Enhanced Recovery Protocol.
The development of enhanced recovery after surgery (ERAS) protocols for patients undergoing radical cystectomy (RC) represents a significant advance in perioperative care. To evaluate gastrointestinal (GI) complications following RC and urinary diversion (UD) using our institutional ERAS protocol. We identified 377 consecutive cases of open RC and UD for which our ERAS protocol was used from May 2012 to December 2015. Exclusion criteria were consent refusal; non-bladder primary disease; palliative, salvage, or additional surgery; and prolonged postoperative intubation. A matched cohort of 144 patients for whom a traditional postoperative protocol (pre-ERAS) was used between 2003 and 2012 was selected for comparison. A total of 292 ERAS patients with median age of 70 yr were included in the study, 65% of whom received an orthotopic neobladder. The median time to first flatus and bowel movement was 2 d. The median length of stay was 4 d. GI complications occurred in 45 patients (15.4%) during the first 30 d following RC, 93% of which were of minor grade. The most common GI complication was postoperative ileus (POI) in 34 cases (11.6%). Some 22 patients (7.5%) required a nasogastric tube, and parenteral nutrition was required in three patients. The rate of 30-d GI complications was significantly lower in the ERAS cohort than in the control group (13% vs 27%; p=0.003), as was the rate of POI (7% vs 23%; p<0.001). This effect was independent of other variables (hazard ratio 0.38, 95% confidence interval 0.18-0.82; p=0.01). Our institutional ERAS protocol for RC is associated with significantly improved perioperative GI recovery and lower rates of GI complications. This protocol can be tested in multi-institutional studies to reduce GI morbidity associated with RC. In this study, we showed that an enhanced recovery protocol for patients undergoing radical cystectomy for bladder cancer was associated with a significantly shorter length of hospital stay and lower rates of gastrointestinal complications, especially postoperative ileus.


HIV prevalence and risk among heterosexual methamphetamine injectors in California.
This study funded by Centers for Disease Control compares HIV prevalence and risk behavior among heterosexual methamphetamine (n = 428) and nonmethamphetamine (n = 878) injectors in California, USA, during 2001-2003. While HIV was not highly prevalent among methamphetamine injectors (3%), sexual and injection risk behaviors were highly prevalent (ranging from 21% to 72%). In multivariate analyses, methamphetamine injectors had higher odds than nonmethamphetamine injectors of unprotected vaginal intercourse and sex with five or more sexual partners in the past 6 months and of distributive and receptive syringe sharing in the past 30 days. There was no significant difference in HIV sero-status by methamphetamine use. Suggestions are made for designing HIV prevention programs. The study's limitations are noted.


Novel Dry-Lab Training Method for Totally Endoscopic Coronary Anastomosis: A Pilot Study.
We describe our original dry-lab training system for nonrobotic and beating heart endoscopic coronary artery anastomosis. All the materials used for this training were commercially available. We selected a boxed machine, which can produce pulsatile movements of artificial vessels, and on its roof, we installed a two-dimensional home video camera and a monitor. A multiple-holed plate was placed in front of the machine, and through these holes, a trainee inserted endoscopic surgical instruments and anastomosed the artificial vessels by running fashion while watching the monitor. This training program has four stages. During the first stage, a trainee has to demonstrate mastery in conducting a conventional off-pump coronary artery anastomosis without assistance. The second stage is the "nonbeating" version, and the third stage is the "beating" version with the model mentioned previously. After a trainee gets accustomed to the third stage, the original artificial vessel is replaced with an extremely fragile one, and this is the fourth stage. Our trainee conducted one hundred fourth-stage anastomoses and each procedure was recorded with the video camera. We analyzed several factors from the videos and evaluated the efficacy of the training method. We compared the outcomes of the first 50 consecutive anastomoses with the following 50 ones and described the learning curves. The comparison showed a significant decrease in anastomotic time and vessel injury. We considered the quality of anastomosis acceptable after 47 anastomoses, and anastomotic time fell below 15 minutes at the 81st training at the fourth stage. Our dry-lab system might be an effective training method for endoscopic coronary anastomosis.


Source of perceived social support and cognitive change: an 8-year prospective cohort study.
This study explored the longitudinal association between overall and individual sources of social support and global cognitive function in older adults.Methods:Data were drawn from three waves (2006, 2010 and 2014) of the Health and Retirement Study (HRS). The analytic sample included participants aged 65 and above who were married and had at least one child (N = 1319). Global cognitive function was measured through a 35-point Telephone Interview Cognitive Screen (TICS). Perceived social support was measured via questions across four sources of support (spouse, child, other family members, and friends). Analyses were conducted using Hierarchical Linear Modeling (HLM) with the addition of a cross-lagged panel model (CLPM). There was no significant association between perceived overall social support and global cognitive function over time (β=-0.02, p=0.19). However, changes in perceived support from children were positively associated with changes in global cognition (β=0.05,p<0.01). In contrast, changes in perceived support from other family members were negatively associated with changes in cognitive function (β=-0.07,p<0.01). Our findings highlight the importance of examining perceived social support from specific elements of one's social networks, rather than in an aggregated variable. Although the positive effect of perceived support from children may be small to moderate, the findings could provide a target for interventions to protect the cognitive function of older adults.


Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.
Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.


Protective niche for Borrelia burgdorferi to evade humoral immunity.
The Lyme disease spirochete, Borrelia burgdorferi, is an extracellular microbe that causes persistent infection despite the development of strong immune responses against the bacterium. B. burgdorferi expresses several ligand-binding lipoproteins, including the decorin-binding proteins (Dbps) A and B, which may mediate attachment to decorin, a major component of the host extracellular matrix during murine infection. We show that B. burgdorferi was better protected in the joints and skin, two tissues with a higher decorin expression, than in the urinary bladder and heart, two tissues with a lower decorin expression, during chronic infection of wild-type mice. Targeted disruption of decorin alone completely abolished the protective niche in chronically infected decorin-deficient mice but did not affect the spirochete burden during early infection. The nature of protection appeared to be specific because the spirochetes with higher outer surface protein C expression were not protected while the protective niche seemed to favor the spirochetes with a higher dbpA expression during chronic infection. These data suggest that spirochetal DbpA may interact with host decorin during infection and such interactions could be a mechanism that B. burgdorferi uses to evade humoral immunity and establish chronic infection.


Multifractal analysis of microvasculature in health and disease.
A growing body of evidence suggests that there is a strong association between neurodegenerative diseases such as Alzheimer's Diseases and the abnormality of the cerebral vasculature, in particular the microvessels/capillaries that are responsible for the exchange of nutrients across the blood-brain barrier [1]. Many microvessels are described as being kinked or distorted [2], implying that they are modified by some destructive process. Imaging devices such as microCT can achieve resolutions on the order of several µm, allowing imaging the three dimensional (3D) microvasculature down to the capillary level. However, the main weakness of using microCT for vascular research is considered to be the lack of software for 3D quantification of microvasculature and microvascular image databases for developing and testing algorithms. In this paper we describe a multifractal analysis method for the microvasculature automatically segmented from microCT images of the mouse brain. Due to the lack of a benchmark microCT image database, the method has been tested using a surrogate database--a publicly available retinal vessel database. The results are preliminary indication of the multifractal properties of mouse brain vasculature. A potential solution to automated classification of healthy and disease brains are discussed.


Schistocerca neuropeptides - An update.
We compiled a comprehensive list of 67 precursor genes encoding neuropeptides and neuropeptide-like peptides using the Schistocerca gregaria genome and several transcriptome datasets. 11 of these 67 precursor genes have alternative transcripts, bringing the total number of S. gregaria precursors identified in this study to 81. Based on this precursor information, we used different mass spectrometry approaches to identify the putative mature, bioactive peptides processed in the nervous system of S. gregaria. The thereby generated dataset for S. gregaria confirms significant conservation of the entire neuropeptidergic gene set typical of insects and also contains precursors typical of Polyneoptera only. This is in striking contrast to the substantial losses of peptidergic systems in some holometabolous species. The neuropeptidome of S. gregaria, apart from species-specific sequences within the known range of variation, is quite similar to that of Locusta migratoria and even to that of less closely related Polyneoptera. With the S. gregaria peptidomics data presented here, we have thus generated a very useful source of information that could also be relevant for the study of other polyneopteran species.


Predictors of CD4+ lymphocyte count among HIV-seropositive and HIV-seronegative pregnant women in Dar es Salaam, Tanzania.
To determine the predictors of CD4+ lymphocyte count among pregnant women in Dar es Salaam, Tanzania. Between 04/1995 and 03/1997, HIV-seropositive (n=1,027) and HIV-seronegative (n=280) pregnant women were interviewed to obtain socio-demographic characteristics. Later, blood samples was collected for determination of T-lymphocyte subsets and other haematological indices. CD4+ lymphocyte count was significantly higher among HIV-seronegative women (mean=770 cells/mm3, standard deviation (SD)=232 cells/mm3) than HIV-seropositive women (mean=422 cells/mm3, SD=205 cells/mm3). Most HIV-seropositive women were asymptomatic, in WHO clinical stage 1 (84.3%). Among HIV-seropositive women, total white blood count (WBC) and erythrocyte sedimentation rate (ESR) remained significantly correlated with CD4+ after adjusting for other predictors in multivariate analyses. For women of average age 25 years, the CD4+ lymphocyte count increased by about 16 cells/mm3 for each increment of 1000 WBC cells/mm3, while each 10 mm/hr increase in ESR was associated with a reduction of CD4+ lymphocyte count of about 8 cells/mm3. These results show that simple and inexpensive haematological indices cannot be recommended for use as alternative measures of HIV-related immunosuppression in this population of mainly asymptomatic women.


Muscle Tissue Labeling of Human Lower Limb in Multi-Channel mDixon MR Imaging: Concepts and Applications.
With increasing resolutions and number of acquisitions, medical imaging more and more requires computer support for interpretation as currently not all imaging data is fully used. In our work, we show how multi-channel images can be used for robust air masking and reliable muscle tissue detection in the human lower limb. We exploit additional channels that are usually discarded in clinical routine. We use the common mDixon acquisition protocol for MR imaging. A series of thresholding, morphological, and connectivity operations is used for processing. We demonstrate our fully automated approach on four subjects and present a comparison with manual labeling. We discuss how this work is used for advanced and intuitive visualization, the quantification of tissue types, pose estimation, initialization of further segmentation methods, and how it could be used in clinical environments.


Cytokinins modulate auxin-induced organogenesis in plants via regulation of the auxin efflux.
Postembryonic de novo organogenesis represents an important competence evolved in plants that allows their physiological and developmental adaptation to changing environmental conditions. The phytohormones auxin and cytokinin (CK) are important regulators of the developmental fate of pluripotent plant cells. However, the molecular nature of their interaction(s) in control of plant organogenesis is largely unknown. Here, we show that CK modulates auxin-induced organogenesis (AIO) via regulation of the efflux-dependent intercellular auxin distribution. We used the hypocotyl explants-based in vitro system to study the mechanism underlying de novo organogenesis. We show that auxin, but not CK, is capable of triggering organogenesis in hypocotyl explants. The AIO is accompanied by endogenous CK production and tissue-specific activation of CK signaling. CK affects differential auxin distribution, and the CK-mediated modulation of organogenesis is simulated by inhibition of polar auxin transport. CK reduces auxin efflux from cultured tobacco cells and regulates expression of auxin efflux carriers from the PIN family in hypocotyl explants. Moreover, endogenous CK levels influence PIN transcription and are necessary to maintain intercellular auxin distribution in planta. Based on these findings, we propose a model in which auxin acts as a trigger of the organogenic processes, whose output is modulated by the endogenously produced CKs. We propose that an important mechanism of this CK action is its effect on auxin distribution via regulation of expression of auxin efflux carriers.