Functional coupling of parietal α rhythms is enhanced in athletes before visuomotor performance: a coherence electroencephalographic study.
It has been shown that elite pistol shooters are characterized by a power increase of wide cortical electroencephalographic (EEG) alpha (about 8-12 Hz) and beta (about 14-35 Hz) rhythms during the preparation of air pistol shots, possibly related to selective attentional and "neural efficiency" processes [Del Percio C, Babiloni C, Bertollo M, Marzano N, Iacoboni M, Infarinato F, Lizio R, Stocchi M, Robazza C, Cibelli G, Comani S, Eusebi F (2009a) Hum Brain Mapp 30(11):3527-3540; Del Percio C, Babiloni C, Marzano N, Iacoboni M, Infarinato F, Vecchio F, Lizio R, Aschieri P, Fiore A, Toràn G, Gallamini M, Baratto M, Eusebi F (2009b) Brain Res Bull 79(3-4):193-200]. Here, we tested the hypothesis that such processes are associated with an enhanced functional coupling of posterior cortical regions involved in task-relevant attentional processes and visuo-motor transformations. To this aim, between-electrodes spectral coherence was computed from spatially enhanced EEG data collected during a previous study (i.e. right handed 18 elite air pistol shooters and 10 matched non-athletes; augmented 10-20 system; surface Laplacian estimation). Theta (about 4-6 Hz), low-frequency alpha (about 8-10 Hz), high-frequency alpha (about 10-12 Hz), low-frequency beta (14-22 Hz), high-frequency beta (23-35 Hz), and gamma (36-44 Hz) bands were considered. Statistical results showed that intra-hemispheric low-frequency alpha (parietal-temporal and parietal-occipital regions), high-frequency alpha (parietal-temporal and parietal-occipital regions), high-frequency beta, and gamma (parietal-temporal regions) coherence values were stable in amplitude in the elite athletes but not in the non-athletes during the preparation of pistol shots. The same applies to inter-hemispheric low-frequency alpha (parietal regions), high-frequency alpha (parietal regions), high-frequency beta and gamma coherence values. These findings suggest that under the present experimental conditions, elite athletes are characterized by the stabilization of functional coupling of preparatory EEG rhythms between "visuo-spatial" parietal area and other posterior cortical areas.


Robustness of positional specification by the Hedgehog morphogen gradient.
Spatial gradients of Hedgehog signalling play a central role in many patterning events during animal development, regulating cell fate determination and tissue growth in a variety of tissues and developmental stages. Experimental evidence suggests that many of the proteins responsible for regulating Hedgehog signalling and transport are themselves targets of Hedgehog signalling, leading to multiple levels of feedback within the system. We use mathematical modelling to analyse how these overlapping feedbacks combine to regulate patterning and potentially enhance robustness in the Drosophila wing imaginal disc. Our results predict that the regulation of Hedgehog transport and stability by glypicans, as well as multiple overlapping feedbacks in the Hedgehog response network, can combine to enhance the robustness of positional specification against variability in Hedgehog levels. We also discuss potential trade-offs between robustness and additional features of the Hedgehog gradient, such as signalling range and size regulation.


WordlePlus: Expanding Wordle's Use through Natural Interaction and Animation.
Wordle has been commonly used to summarize texts, with each word size-coded by its frequency of occurrences--the more often a word occurs in texts, the bigger it is. The interactive authoring tool WordlePlus leverages natural interaction and animation to give users more control over wordle development. WordlePlus supports direct manipulation of words with pen and touch interaction. It introduces two-word multitouch manipulation, such as concatenating and grouping two words, and provides pen interaction for adding and deleting words. In addition, WordlePlus employs animation to help users create more dynamic and engaging wordles.


Nuclear Cardio-Oncology.
Nuclear cardio-oncology is a specialized field that combines aspects of nuclear medicine, cardiology, and oncology to diagnose and manage cardiovascular complications in cancer patients. It focuses on the assessment of cardiovascular health and the detection of potential heart-related side effects caused by cancer treatments.


Rapid seasonal-like regression of the adult avian song control system.
We analyzed how rapidly avian song control nuclei regress after testosterone (T) withdrawal. Regression of neuronal attributes resulting from T withdrawal has been observed in several animal models. The time course over which regression occurs is not known, however. To address this issue, we castrated adult male white-crowned sparrows and rapidly shifted them to short-day photoperiods after being held under breeding conditions (long-day photoperiod and systemic T exposure) for 3 weeks. We found that the volume of one song nucleus, HVC, regressed 22% within 12 h after T withdrawal. Changes in HVC neuron density after T withdrawal were dynamic; density increased at 12 h and then decreased by 4 days. HVC neuron number was reduced by 26% by 4 days. The volumes of Area X and the robust nucleus of the arcopallium (RA) were significantly regressed by 7 and 20 days, respectively. RA somatic area and neuronal spacing were significantly reduced by 2 days. The rapidity of HVC regression is unprecedented among vertebrate models of hormone-sensitive neural circuits. These results reveal that the rapid regression of the song control system provides a model for the important role sex steroid hormones play in mediating adult neural plasticity and in neuroprotection.


Blood lymphocyte subpopulations and antibody dependent, cell-mediated cytotoxicity (ADCC) in alopecia areata and universalis.
T-lymphocyte subpopulations and antibody-dependent, cell-mediated cytotoxicity (ADCC) were studied in patients with alopecia areata and universalis. The proportions of T-cells with the receptors for IgG (Tg) and T-cells with receptor for IgM (Tm) were determined in 16 cases. The ADCC of unfractionated lymphocytes was examined in 5 cases. A higher proportion of Tg-cells (T-cell with low affinity for sheep red cells) and a more pronounced ADCC of the peripheral lymphocytes were found in patients with alopecia areata and universalis than in age- and sex-matched normal donors.


Nonuniform sampling and maximum entropy reconstruction in multidimensional NMR.
NMR spectroscopy is one of the most powerful and versatile analytic tools available to chemists. The discrete Fourier transform (DFT) played a seminal role in the development of modern NMR, including the multidimensional methods that are essential for characterizing complex biomolecules. However, it suffers from well-known limitations: chiefly the difficulty in obtaining high-resolution spectral estimates from short data records. Because the time required to perform an experiment is proportional to the number of data samples, this problem imposes a sampling burden for multidimensional NMR experiments. At high magnetic field, where spectral dispersion is greatest, the problem becomes particularly acute. Consequently multidimensional NMR experiments that rely on the DFT must either sacrifice resolution in order to be completed in reasonable time or use inordinate amounts of time to achieve the potential resolution afforded by high-field magnets. Maximum entropy (MaxEnt) reconstruction is a non-Fourier method of spectrum analysis that can provide high-resolution spectral estimates from short data records. It can also be used with nonuniformly sampled data sets. Since resolution is substantially determined by the largest evolution time sampled, nonuniform sampling enables high resolution while avoiding the need to uniformly sample at large numbers of evolution times. The Nyquist sampling theorem does not apply to nonuniformly sampled data, and artifacts that occur with the use of nonuniform sampling can be viewed as frequency-aliased signals. Strategies for suppressing nonuniform sampling artifacts include the careful design of the sampling scheme and special methods for computing the spectrum. Researchers now routinely report that they can complete an N-dimensional NMR experiment 3(N-1) times faster (a 3D experiment in one ninth of the time). As a result, high-resolution three- and four-dimensional experiments that were prohibitively time consuming are now practical. Conversely, tailored sampling in the indirect dimensions has led to improved sensitivity. Further advances in nonuniform sampling strategies could enable further reductions in sampling requirements for high resolution NMR spectra, and the combination of these strategies with robust non-Fourier methods of spectrum analysis (such as MaxEnt) represent a profound change in the way researchers conduct multidimensional experiments. The potential benefits will enable more advanced applications of multidimensional NMR spectroscopy to study biological macromolecules, metabolomics, natural products, dynamic systems, and other areas where resolution, sensitivity, or experiment time are limiting. Just as the development of multidimensional NMR methods presaged multidimensional methods in other areas of spectroscopy, we anticipate that nonuniform sampling approaches will find applications in other forms of spectroscopy.


Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation.
The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which cells that are not exposed to ionizing radiation exhibit responses typically associated with direct radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). There is accumulating evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free-radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect inter-related aspects of inflammatory-type responses to radiation-induced stress and injury and contribute to the variety of pathological consequences of radiation exposures.


Has Germany's temporary VAT rates cut as part of the COVID-19 fiscal stimulus boosted growth?
On 3 June 2020, the German government announced a EUR 130 billion fiscal stimulus package to stimulate market demand and jumpstart the economy in the wake of the COVID-19 pandemic lockdown in the spring of 2020. The most prominent measure of this package is an unconventional fiscal policy in the form of a temporary VAT rates cut for six months, from 1 July to 31 December 2020. Employing a dynamic stochastic general equilibrium (DSGE) framework, we study the efficiency of the VAT tax rates cut for ameliorating the consequences of the pandemic recession. The simulation of the calibrated DSGE model yields a tax policy-induced real GDP increase of about 0.3% points for 2020.


[Clinical features of pediatric multiple sclerosis: epidemiology and treatment].
Multiple sclerosis (MS) in children is essentially not different from MS in adults; however, in children, it is sometimes difficult to distinguish MS from other demyelinating diseases. The main reason for this is that acute encephalitis/encephalopathy associated with infectious diseases, especially acute disseminated encephalomyelitis (ADEM), often causes demyelinating events in the central nervous system in childhood, and that the demyelinating episodes of MS in younger children clinically resemble ADEM events. Therefore, a number of studies on pediatric demyelinating diseases have been conducted to elucidate the clinical features of pediatric MS. In this article, the clinical features of pediatric MS in Japan were reviewed on the basis of the results of a nationwide survey as well as those in other countries.


Substrate transport and anion permeation proceed through distinct pathways in glutamate transporters.
Advances in structure-function analyses and computational biology have enabled a deeper understanding of how excitatory amino acid transporters (EAATs) mediate chloride permeation and substrate transport. However, the mechanism of structural coupling between these functions remains to be established. Using a combination of molecular modeling, substituted cysteine accessibility, electrophysiology and glutamate uptake assays, we identified a chloride-channeling conformer, iChS, transiently accessible as EAAT1 reconfigures from substrate/ion-loaded into a substrate-releasing conformer. Opening of the anion permeation path in this iChS is controlled by the elevator-like movement of the substrate-binding core, along with its wall that simultaneously lines the anion permeation path (global); and repacking of a cluster of hydrophobic residues near the extracellular vestibule (local). Moreover, our results demonstrate that stabilization of iChS by chemical modifications favors anion channeling at the expense of substrate transport, suggesting a mutually exclusive regulation mediated by the movement of the flexible wall lining the two regions.


Repertoire, genealogy and genomic organization of cruzipain and homologous genes in Trypanosoma cruzi, T. cruzi-like and other trypanosome species.
Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.


ADSA Foundation Scholar Award: Early-life exposure to hyperthermia: Productive and physiological outcomes, costs, and opportunities.
Global rising temperature is a considerable threat to livestock production and an impediment to animal welfare. In fact, the 5 warmest years on record have occurred since 2016. Although the effect of heat stress on lactating cattle is well recognized and extensively studied, it is increasingly evident that rising temperatures will affect dairy cattle of all ages and lactation states. However, the extent and consequences of this effect are less understood and often overlooked in the literature and dairy industry. Early-life experiences, such as exposure to hyperthermia, can have life-long implications for health and productivity. This review highlights the body of work surrounding the effects of heat-stress exposure in young dairy cattle, including the prenatal fetus (in utero), postnatal calves (preweaning), and growing heifers, which are all categories that are typically not considered for heat-stress abatement on farm. Insights into the physiological and molecular mechanisms that might explain the adverse phenotypic outcomes of heat-stress exposure at different stages of development are also discussed. The estimated economic loss of in utero hyperthermia is addressed, and the ties between biological findings and opportunities for the application of cooling management interventions on farm are also presented. Our research highlights the importance of heat-stress abatement strategies for dry-pregnant cows to ensure optimal multigenerational productivity and showcases the benefits of cooling neonatal calves and growing heifers. Understanding the implications of heat stress at all life stages from a physiological, molecular, economic, and welfare perspective will lead to the development of novel and refined practices and interventions to help overcome the long-lasting effects of climate change in the dairy industry.


The Use of Myelinating Cultures as a Screen of Glycomolecules for CNS Repair.
In vitro cell-based assays have been fundamental in modern drug discovery and have led to the identification of novel therapeutics. We have developed complex mixed central nervous system (CNS) cultures, which recapitulate the normal process of myelination over time and allow the study of several parameters associated with CNS damage, both during development and after injury or disease. In particular, they have been used as a reliable screen to identify drug candidates that may promote (re)myelination and/or neurite outgrowth. Previously, using these cultures, we demonstrated that a panel of low sulphated heparin mimetics, with structures similar to heparan sulphates (HSs), can reduce astrogliosis, and promote myelination and neurite outgrowth. HSs reside in either the extracellular matrix or on the surface of cells and are thought to modulate cell signaling by both sequestering ligands, and acting as co-factors in the formation of ligand-receptor complexes. In this study, we have used these cultures as a screen to address the repair potential of numerous other commercially available sulphated glycomolecules, namely heparosans, ulvans, and fucoidans. These compounds are all known to have certain characteristics that mimic cellular glycosaminoglycans, similar to heparin mimetics. We show that the N-sulphated heparosans promoted myelination. However, O-sulphated heparosans did not affect myelination but promoted neurite outgrowth, indicating the importance of structure in HS function. Moreover, neither highly sulphated ulvans nor fucoidans had any effect on remyelination but CX-01, a low sulphated porcine intestinal heparin, promoted remyelination in vitro. These data illustrate the use of myelinating cultures as a screen and demonstrate the potential of heparin mimetics as CNS therapeutics.


Decarboxylation of alpha-keto acids by Streptococcus lactis var. maltigenes.
Decarboxylation rates for a series of C-3 to C-6 alpha-keto acids were determined in the presence of resting cells and cell-free extracts of Streptococcus lactis var. maltigenes. The C-5 and C-6 acids branched at the penultimate carbon atom were converted most rapidly to the respective aldehydes in the manner described for alpha-carboxylases. Pyruvate and alpha-ketobutyrate did not behave as alpha-carboxylase substrates, in that O(2) was absorbed when they were reacted with resting cells. The same effect with pyruvate was noted in a nonmalty S. lactis, accounting for CO(2) produced by some "homofermentative" streptococci. Mixed substrate reactions indicated that the same enzyme was responsible for decarboxylation of alpha-ketoisocaproate and alpha-ketoisovalerate, but it appeared unlikely that this enzyme was responsible for the decarboxylation of pyruvate. Ultrasonic disruption of cells of the malty culture resulted in an extract inactive for decarboxylation of pyruvate in the absence of ferricyanide. Dialyzed cell-free extracts were inactive against all keto acids and could not be reactivated.


Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis.
Tissue-resident and recruited macrophages contribute to both host defense and pathology. Multiple macrophage phenotypes are represented in diseased tissues, but we lack deep understanding of mechanisms controlling diversification. Here, we investigate origins and epigenetic trajectories of hepatic macrophages during diet-induced non-alcoholic steatohepatitis (NASH). The NASH diet induced significant changes in Kupffer cell enhancers and gene expression, resulting in partial loss of Kupffer cell identity, induction of Trem2 and Cd9 expression, and cell death. Kupffer cell loss was compensated by gain of adjacent monocyte-derived macrophages that exhibited convergent epigenomes, transcriptomes, and functions. NASH-induced changes in Kupffer cell enhancers were driven by AP-1 and EGR that reprogrammed LXR functions required for Kupffer cell identity and survival to instead drive a scar-associated macrophage phenotype. These findings reveal mechanisms by which disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct gene expression programs and corresponding functions.


Detection and genetic characterization of porcine deltacoronavirus in Tibetan pigs surrounding the Qinghai-Tibet Plateau of China.
Porcine deltacoronavirus (PDCoV) is a recently discovered RNA virus that belongs to the family Coronaviridae and genus Deltacoronavirus. This virus causes enteric disease in piglets that is characterized by enteritis and diarrhoea. In our present investigation, 189 diarrhoeic samples were collected between July 2016 and May 2017 from Tibetan pigs inhabiting in three different provinces surrounding the Qinghai-Tibet Plateau of China. We then applied the molecular-based method of reverse transcription polymerase chain reactions (RT-PCRs) to detect the presence of PDCoV in collected samples, and RT-PCR indicated that the prevalence of PDCoV was 3.70% (7/189) in Tibetan pigs. Four of 7 PDCoV-positive pigs were monoinfections of PDCoV, three samples were co-infections of PDCoV with porcine epidemic diarrhoea virus (PEDV), and 52 (27.51%) samples were positive for PEDV. Four strains with different full-length genomes were identified (CHN/GS/2016/1, CHN/GS/2016/2, CHN/GS-/2017/1 and CHN/QH/2017/1), and their genomes were used to analyse the characteristics of PDCoV currently prevalent in Tibetan pigs. We found a 3-nt insertion in the spike gene in four strains in Tibetan pigs. Phylogenetic analysis of the complete genome and spike and nucleocapsid gene sequences revealed that these strains shared ancestors with the strain CHN-AH-2004, which was found in pigs from the Anhui province of China mainland. However, PDCoV strains from Tibetan pigs formed different branches within the same cluster, implying continuous evolution in the field. Our present findings highlight the importance of epidemiologic surveillance to limit the spread of PDCoV in livestock at high altitudes in China.


Functional differentiation of 3-ketosteroid Δ1-dehydrogenase isozymes in Rhodococcus ruber strain Chol-4.
The Rhodococcus ruber strain Chol-4 genome contains at least three putative 3-ketosteroid Δ1-dehydrogenase ORFs (kstD1, kstD2 and kstD3) that code for flavoenzymes involved in the steroid ring degradation. The aim of this work is the functional characterization of these enzymes prior to the developing of different biotechnological applications. The three R. ruber KstD enzymes have different substrate profiles. KstD1 shows preference for 9OHAD and testosterone, followed by progesterone, deoxy corticosterone AD and, finally, 4-BNC, corticosterone and 19OHAD. KstD2 shows maximum preference for progesterone followed by 5α-Tes, DOC, AD testosterone, 4-BNC and lastly 19OHAD, corticosterone and 9OHAD. KstD3 preference is for saturated steroid substrates (5α-Tes) followed by progesterone and DOC. A preliminary attempt to model the catalytic pocket of the KstD proteins revealed some structural differences probably related to their catalytic differences. The expression of kstD genes has been studied by RT-PCR and RT-qPCR. All the kstD genes are transcribed under all the conditions assayed, although an additional induction in cholesterol and AD could be observed for kstD1 and in cholesterol for kstD3. Co-transcription of some correlative genes could be stated. The transcription initiation signals have been searched, both in silico and in vivo. Putative promoters in the intergenic regions upstream the kstD1, kstD2 and kstD3 genes were identified and probed in an apramycin-promoter-test vector, leading to the functional evidence of those R. ruber kstD promoters. At least three putative 3-ketosteroid Δ1-dehydrogenase ORFs (kstD1, kstD2 and kstD3) have been identified and functionally confirmed in R. ruber strain Chol-4. KstD1 and KstD2 display a wide range of substrate preferences regarding to well-known intermediaries of the cholesterol degradation pathway (9OHAD and AD) and other steroid compounds. KstD3 shows a narrower substrate range with a preference for saturated substrates. KstDs differences in their catalytic properties was somehow related to structural differences revealed by a preliminary structural modelling. Transcription of R. ruber kstD genes is driven from specific promoters. The three genes are constitutively transcribed, although an additional induction is observed in kstD1 and kstD3. These enzymes have a wide versatility and allow a fine tuning-up of the KstD cellular activity.


Statistics of carrier-cargo complexes.
We explore the statistics of assembling soft-matter building blocks to investigate the uptake and encapsulation of cargo particles by carriers engulfing their load. While the such carrier-cargo complexes are important for many applications out of equilibrium, such as drug delivery and synthetic cell encapsulation, we uncover here the basic statistical physics in minimal hard-core-like models for particle uptake. Introducing an exactly solvable equilibrium model in one dimension, we demonstrate that the formation of carrier-cargo complexes can be largely tuned by both the cargo concentration and the carriers' interior size. These findings are intuitively explained by interpreting the internal free space (partition function) of the cargo inside a carrier as its engulfment strength, which can be mapped to an external control parameter (chemical potential) of an additional effective particle species. Assuming a hard carrier membrane, such a mapping can be exactly applied to account for multiple cargo uptake involving various carrier or cargo species and even attractive uptake mechanisms, while soft interactions require certain approximations. We further argue that the Boltzmann occupation law identified within our approach is broken when particle uptake is governed by nonequilibrium forces. Speculating on alternative occupation laws using effective parameters, we put forward a Bose-Einstein-like phase transition associated with polydisperse carrier properties.


The Effect of Sevoflurane Plus Propofol on Pain and Complications after Laminectomy: A Randomized Double Blind Clinical Trial.
Pain is one of the most important reasons for the patients concern after surgery. The perfect sedative should have properties like rapid onset, least pain and adverse effects. To assess the effect of sevoflurane plus propofol on postoperative pain, haemodynamic stability and complication after lumbar disc surgery. This was a randomized double- blind clinical trial. A total of 75 patients scheduled for elective lumbar disc surgery with simple random sampling design received sevoflurane (n=25, induced with Thiopentone and maintained with sevoflurane), propofol (n=25, induced and maintained with propofol) and sevoflurane plus propofol (n=25, induced with propofol and maintained with sevoflurane). Visual Analog Scale (VAS) was used to determine the intensity of postoperative pain. Complications after surgery and haemodynamic changes during surgery were recorded. The mean pain intensity and morphine consumption in the sevoflurane plus propofol group was lower compared to the propofol and sevoflurane groups at different intervals (p<0.001). The prevalence of shivering, nausea and vomiting in the sevoflurane plus propofol group was 24%, 28%, 28% respectively vs sevoflurane group 32%, 60%, 48% respectively and propofol group 32%, 16%, 12% respectively with p-value > 0.05, <0.001, <0.05 respectively. The mean blood pressure and heart rate were significantly lower in the sevoflurane plus propofol group compared to the propofol and sevoflurane groups (p<0.001). According to the effect on pain and complications after lumbar disc surgery sevoflurane plus propofol can be regarded as safe and alternative drug in general anaesthesia for these patients.


Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.
In this study, we describe the rapid identification of potent binders for the WD40 repeat domain (WDR) of DCAF1. This was achieved by two rounds of iterative focused screening of a small set of compounds selected on the basis of internal WDR domain knowledge followed by hit expansion. Subsequent structure-based design led to nanomolar potency binders with a clear exit vector enabling DCAF1-based bifunctional degrader exploration.


The future of neuroepigenetics in the human brain.
Complex mechanisms shape the genome of brain cells into transcriptional units, clusters of condensed chromatin, and many other features that distinguish between various cell types and developmental stages sharing the same genetic material. Only a few years ago, the field's focus was almost entirely on a single mark, CpG methylation; the emerging complexity of neuronal and glial epigenomes now includes multiple types of DNA cytosine methylation, more than 100 residue-specific posttranslational histone modifications and histone variants, all of which superimposed by a dynamic and highly regulated three-dimensional organization of the chromosomal material inside the cell nucleus. Here, we provide an update on the most innovative approaches in neuroepigenetics and their potential contributions to approach cognitive functions and disorders unique to human. We propose that comprehensive, cell type-specific mappings of DNA and histone modifications, chromatin-associated RNAs, and chromosomal "loopings" and other determinants of three-dimensional genome organization will critically advance insight into the pathophysiology of the disease. For example, superimposing the epigenetic landscapes of neuronal and glial genomes onto genetic maps for complex disorders, ranging from Alzheimer's disease to schizophrenia, could provide important clues about neurological function for some of the risk-associated noncoding sequences in the human genome.


Effect of phytol in forage on phytanic acid content in cow's milk.
Bioactive compounds in ruminant products are related to functional compounds in their diets. Therefore, this study aimed to explore the effect of forage sources, Italian ryegrass (IR) silage vs corn silage (CS) in the total mixed ration (TMR), on milk production, milk composition, and phytanic acid content in milk, as well as on the extent of conversion of dietary phytol to milk phytanic acid. Phytanic acid content in milk was investigated for cows fed a TMR containing either IR silage or CS using 17 cows over three periods of 21 days each. In periods 1 and 3, cows were fed CS-based TMR (30% CS), while in period 2, cows were fed IR silage-based TMR (20% IR silage and10% CS). The results showed that there were no differences in fat, protein, lactose, solidsnot-fat, somatic cell count, and fatty acid composition of milk among the three experimental periods. There were no differences in the plasma concentration of glucose, triglycerides, total cholesterol, and nonesterified fatty acids among the three experimental periods, while the blood urea nitrogen was higher (p<0.05) in period 2. The milk phytanic acid content was higher (p<0.05) in period 2 (13.9 mg/kg) compared with periods 1 (9.30 mg/kg) and 3 (8.80 mg/kg). Also, the phytanic acid content in the feces was higher (p<0.05) in period 2 (1.65 mg/kg dry matter [DM]) compared with period 1 (1.15 mg/kg DM), and 3 (1.17 mg/kg DM). Although the phytol contents in feces did not differ among the three feeding periods, the conversion ratio from dietary phytol to milk phytanic acid was estimated to be only 2.6%. Phytanic acid content in cow's milk increases with increasing phytol content in diets. However, phytol might not be completely metabolized in the rumen and phytanic acid, in turn, might not be completely recovered into cow's milk. The change of phytanic acid content in milk may be positively correlated with the change of phytol in the diet within a short time.


Endothelin receptor antagonists: effect of serum albumin on potency and comparison of pharmacological characteristics.
Endothelins (ETs) are 21-amino acid peptides that bind to membrane receptors to initiate pathophysiological effects. Two types of ET receptors, ETA and ETB, have been identified. Various ET receptor antagonists are being developed as therapeutic agents. This report examines the effects of bovine serum albumin (BSA) on the potency of ET receptor antagonists and compares five ET receptor antagonists. Competition studies show that in the absence of BSA, A-127722 and L-749329 inhibited ET-1 binding to ETA receptor with the same IC50 value of 0.09 nM. Addition of increasing concentrations of BSA incrementally decreased the potency of the antagonists: in the presence of 5% BSA, the IC50 values increased to 4.3 and 820 nM, respectively. Similarly, addition of BSA decreased the potency of antagonists in inhibiting ET-1-stimulated phosphatidylinositol hydrolysis. These results suggest that serum albumin has profound effects on the potencies of ET receptor antagonists. FR139317, PD-156707, L-749329, Ro-47-0203 and A-127722 were then selected for direct comparison under identical experimental conditions with 0.2% BSA. The potency of antagonists was assessed by binding studies for the determination of IC50 and Ki values and by ET-1-stimulated phosphatidylinositol hydrolysis and arachidonic acid release for the determination of IC50 and pA2 values. All five antagonists inhibited ET binding and the biological effects exerted by ET in a competitive mode. The Ki values for A-127722, PD-156707, FR139317, Ro-47-0203 and L-749329 for the ETA receptor were 0.07, 0.38, 0.80, 3.67 and 33.6 nM, respectively. A similar hierarchy was revealed by the functional assays. Our results suggest that the rank order of potency of the antagonists is A-127722 > or = PD-156707 > or = FR139317 > Ro-47-0203 > L-749329.


LoopWeaver: loop modeling by the weighted scaling of verified proteins.
Modeling loops is a necessary step in protein structure determination, even with experimental nuclear magnetic resonance (NMR) data, it is widely known to be difficult. Database techniques have the advantage of producing a higher proportion of predictions with subangstrom accuracy when compared with ab initio techniques, but the disadvantage of also producing a higher proportion of clashing or highly inaccurate predictions. We introduce LoopWeaver, a database method that uses multidimensional scaling to achieve better, clash-free placement of loops obtained from a database of protein structures. This allows us to maintain the above-mentioned advantage while avoiding the disadvantage. Test results show that we achieve significantly better results than all other methods, including Modeler, Loopy, SuperLooper, and Rapper, before refinement. With refinement, our results (LoopWeaver and Loopy consensus) are better than ROSETTA, with 0.42 Å RMSD on average for 206 length 6 loops, 0.64 Å local RMSD for 168 length 7 loops, 0.81Å RMSD for 117 length 8 loops, and 0.98 Å RMSD for length 9 loops, while ROSETTA has 0.55, 0.79, 1.16, 1.42, respectively, at the same average time limit (3 hours). When we allow ROSETTA to run for over a week, it approaches, but does not surpass, our accuracy.


[Apgar score: time to "call it"?]
Virginia Apgar designed the apgar score during a breakfast with colleagues in response to a discussion about the need to evaluate newborns at birth. She scribbled down the score on a piece of paper and the score has been indispensable ever since, not just for reflecting the clinical condition and to indicate whether intervention was needed, but also to predict outcome. The reliability and validity have been often questioned, also in a recent study. Is it time to "call it" and send the score on retirement?


New immunohistochemistry for B-cell lymphoma and Hodgkin lymphoma.
B-cell non-Hodgkin lymphoma is a heterogeneous group of lymphoproliferative malignancies with different clinical behaviors and treatments. It is important to differentiate individual B-cell lymphoma to apply the best treatment and management. Morphology and immunohistochemistry are the primary tools used for diagnosing lymphoma. There is a characteristic pattern of expression with immunohistochemical antibodies in most well-defined B-cell lymphomas. Some cases of B-cell lymphoma, however, show unusual morphologic and immunophenotypic features. The new and sometimes more specific antibodies have been developed recently, which may further define those lymphomas. Only with use of the antibodies over time does their true nature and specificity become evident. To present new antibodies for B-cell lymphoma that enhance the probability for diagnosis or can act as alternate markers in unusual cases, in which a B-cell lymphoma does not present with characteristic immunohistochemical staining, and to present prognostic markers that allow for better management of patients with specific B-cell lymphomas. Data were obtained from literature review and figures from slides in personal practice. The immunohistochemical antibodies presented in this article increase our ability to understand, diagnosis, and manage patients with B-cell lymphoma.


The collagenous nature of amianthoid degeneration of human costal cartilage.
Amianthoid (asbestoid) fibers in aging human costal cartilage are shown to be collagenous both by their electron microscopic appearance and solubilization by clostridial collagenase. The fibers differ morphologically from collagen of dermis, synovium, tendon, fibrocartilage and hyaline articular cartilage in dimension, contour and arrangement. They measure up to 1 mu in width, and their period length is 560 to 620 A. Their thickness, straightness and parallel organization suggest that amianthoid fibers are rigid. Their stability in the face of the preparative technics suggests that cohesive forces rather than spatial apposition through depletion of ground substance operate to hold the component fibrils together. These forces may or may not arise from covalent cross-links.


A Phase I clinical trial of the knee to assess the correlation of gagCEST MRI, delayed gadolinium-enhanced MRI of cartilage and T2 mapping.
Osteoarthritis (OA) is associated with the loss of glycosaminoglycan (GAG) during disease progression, which can be detected by glycosaminoglycan chemical exchange-dependent saturation transfer (gagCEST) MRI. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is considered one of the standard methods for GAG quantification in vivo. This Phase I study assessed the correlation between gagCEST MRI and dGEMRIC in determining cartilage GAG concentration. Standard T2 mapping was used as a comparator with the two other methods. Eight athletic volunteers with no known knee diseases were recruited in this study. The sagittal images of both knees in each volunteer were obtained by a 3T MRI system. GAG concentration was calculated based on fixed charge density (FCD) within articular cartilage as calculated by T1 values obtained from dGEMRIC sequences. Magnetization transfer ratio asymmetry (MTRasym) of the CEST spectrum at 1ppm was determined with gagCEST MRI. T2 values were calculated using a multi-echo turbo spin echo (TSE) sequence. The Pearson correlations among MTRasym were calculated from gagCEST analysis. There was moderate correlation (correlation coefficient r=0.55) between dGEMRIC and gagCEST MRI results. T2 had a low correlation (r=-0.30) with gagCEST and no correlation with dGEMRIC (r=0.003). Both gagCEST and dGEMRIC were able to distinguish between high GAG concentration cartilage compartments (higher than 210mM) and low GAG cartilage compartments (lower than 210mM). dGEMRIC was shown to be a more accurate and sensitive clinical imaging tool in evaluating cartilage GAG levels in vivo. While GagCEST showed less sensitivity to GAG concentration variations than dGEMRIC, further improvements may yet enable gagCEST to be a clinically robust methodology.


Aqueous Solvation of SmI2: A Born-Oppenheimer Molecular Dynamics Density Functional Theory Cluster Approach.
We report the results of Born-Oppenheimer molecular dynamics (BOMD) simulations on the aqueous solvation of the SmI2 molecule at room temperature using the cluster microsolvation approach including 32 water molecules. The electronic structure calculations were done using the M062X hybrid exchange-correlation functional in conjunction with the 6-31G** basis sets for oxygen and hydrogen. For the iodine and samarium atoms the Stuttgart-Köln relativistic effective-core potentials were utilized with their associated valence basis sets. Starting from the optimized geometry of SmI2 embeded in the microsolvation environment, we find a swift substitution of the iodine ions by eight tightly bound water molecules around Sm(II). Through the Sm-O radial distribution function and the evolution of the Sm-O distances, the present study predicts a first rigid Sm(II) solvation shell from 2.6 to 3.4 Å, whose integration leads to a coordination number of 8.4 water molecules, and a second softer solvation sphere from 3.5 to ca. 6 Å. The Sm(II)-O radial distribution function is in excellent agreement with that reported for Sr2+ from EXAFS studies, a fact that can be explained because Sr2+ and Sm2+ have almost identical ionic radii (ca. 1.26 Å) and coordination numbers: 8 for Sr2+ and 8.4 for Sm2+. The theoretical EXAFS spectrum was obtained from the BOMD trajectory and is discussed in the light of the experimental spectra for Sm(III). Once microsolvation is achieved, no water exchange events were found to occur around Sm2+, in agreement with the experimental data for Eu2+ (which has a nearly identical charge-to-ionic radius relation as Sm2+), where the mean residence time of a water molecule in [Eu(H2O)8]2+ is known to be ca. 230 ps.


Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring.
Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.


Are the "myths" of low back pain alive in the general Norwegian population?
The aim of this study was to examine the perception of low back pain care and consequences according to what Deyo refers to as seven "myths" about back pain, in the Norwegian population. In spring 2001, seven questions, corresponding to Deyo's myths, were included in an opinion poll (telephone interviews) of a representative sample (n=1015) of the Norwegian population. In total, 41% of the population held that 'If you have a slipped disc you must have surgery'. Approximately 50% believed that 'X-ray and newer imaging tests can always identify the cause of pain' and 'Most back pain is caused by injury and heavy lifting'. Almost 60% agreed that 'Everyone with back pain should have a spine X-ray'. However, only one-quarter believed that 'If your back hurts, you should take it easy until the pain goes away', and approximately one-fifth believed that 'Back pain is usually disabling'. Only 12% believed that 'Bed rest is the mainstay of therapy'. More individuals in the lower- compared with the higher-educated groups believed in the myths. Information concerning current knowledge on healthcare and health consequences of low back pain had reached only a small part of the general population. The most important factor for lack of knowledge was education. Developing effective methods to promote adequate self-care and treatment and reduce the risk of chronicity of low back pain in the lower-educated groups should be a top priority.


Antimicrobial dosing strategies in critically ill patients with acute kidney injury and high-dose continuous veno-venous hemofiltration.
Delivery of appropriate antimicrobial therapy is a great challenge during continuous veno-venous hemofiltration (CVVH), particularly if the recommended higher doses are applied. The present contribution discusses the principles of drug dosing during CVVH and compares the various proposed dosing strategies. The basic principles underlying removal of antibiotics during CVVH and the published dosing strategies are reviewed. The key factor to consider is the fractional CVVH clearance (FrCVVH). Critical illness and acute kidney injury, however, may dramatically affect the pharmacokinetic properties of a drug and thus FrCVVH. Five dosing strategies have been proposed on the basis of either available references, total creatinine clearance, the reduction in total body clearance, the maintenance dose multiplication factor, or therapeutic drug monitoring. Dose predictions according to the various strategies show reasonable approximations for some but not all antibiotics. The delivery of appropriate antimicrobial therapy during CVVH leaves us with uncertainty and presents a great challenge. To ensure efficacy and prevent toxicity, therapeutic drug monitoring is highly recommended. In the absence of therapeutic drug monitoring, adequate concentrations can only be inferred from clinical response. For nontoxic antibiotics overdosing is preferred to underdosing because the danger of underdosing is far greater than that of overdosing.


Pulmonary Vein Thrombosis: A Recent Systematic Review.
The pulmonary veins (PVs) are the most proximal source of arterial thromboembolism. Pulmonary vein thrombosis (PVT) is a rare but potentially lethal disease; its incidence is unclear, as most of the literature includes case reports. It most commonly occurs as a complica-tion of malignancy, post lung surgery, or atrial fibrillation and can be idiopathic in some cases. Most patients with PVT are commonly asymptomatic or have nonspecific symptoms such as cough, hemoptysis, and dyspnea from pulmonary edema or infarction. The thrombi are typically detected using a variety of imaging modalities including transesophageal echocardiogram (TEE), computed tomography (CT) scanning, magnetic resonance imaging (MRI), or pulmonary angiog-raphy. Treatment should be determined by the obstructing pathological finding and can include antibiotic therapy, anticoagulation, thrombectomy, and/or pulmonary resection. The delay in diagnosing this medical entity can lead to complications including pulmonary infarction, pulmonary edema, right ventricular failure, allograft failure, and peripheral embolism resulting in limb ischemia, stroke, and renal infarction (RI).


The prevalence of dental attrition and its association with factors of age, gender, occlusion, and TMJ symptomatology.
Dental attrition severity in 222 young adults was assessed from dental casts as the sum of the most severe facet in each arch segment. The attrition scores were compared by age, gender, bruxism awareness, prior bite adjustment, orthodontic class, maxillomandibular relationship, and temporomandibular dysfunction symptoms. Awareness of bruxism was not associated with the wear scores and should not be used to define bruxist groups. Attrition scores did not differ significantly between age groups, indicating that notable attrition, when present, often occurs early. Men had higher attrition scores than women (p less than 0.01), despite fewer signs and symptoms. Dental attrition was not associated with the presence or absence of TMJ clicking, TMJ tenderness, or masticatory muscle tenderness. Class II division 2 males had laterotrusive attrition scores lower than those of Class III (p less than 0.05). Class III females had lower incisor attrition scores than did other Angle Classes (p less than 0.05). Discernible dental attrition in a non-patient population was not associated with signs and symptoms of temporomandibular disorders, nor with the occlusal factors studied. These results are compatible with the findings in other studies that point to bruxism as a centrally induced phenomenon common to all people and unrelated to local factors.


Identifying triplet pathways in dilute pentacene films.
Building efficient triplet-harvesting layers for photovoltaic applications requires a deep understanding of the microscopic properties of the components involved and their dynamics. Singlet fission is a particularly appealing mechanism as it generates two excitons from a single photon. However, the pathways of the coupled triplets into free species, and their dependence on the intermolecular geometry, has not been fully explored. In this work, we produce highly ordered dilute pentacene films with distinct parallel and herringbone dimers and aggregates. Using electron paramagnetic resonance spectroscopy, we provide compelling evidence for the formation of distinct quintet excitons in ambient conditions, with intrinsically distinctive electronic and kinetic properties. We find that the ability of quintets to separate into free triplets is promoted in the parallel dimers and this provides molecular design rules to control the triplets, favouring either enhanced photovoltaic efficiency (parallel) or strongly bound pairs that could be exploited for logic applications (herringbone).


Coexistence of large-area topological pseudospin and valley states in a tri-band heterostructure system.
The rapid development of topological photonics has significantly revolutionized our comprehension of electromagnetic wave manipulation in recent decades. Recent research exploiting large-area topological states inserts an additional gapless PC structure between topologically trivial and nontrivial PCs, effectively introducing the mode width degree of freedom. Nevertheless, these heterostructures mainly support only single-type waveguide states operating within a single frequency band. To address these limitations, we propose a novel, to the best of our knowledge, tri-band three-layer heterostructure system, supporting both large-area pseudospin- and valley-locked states. The system showcases tunable mode widths with different operational bandwidths. Moreover, the heterostructures exhibit inherent topological characteristics and reflection-free interfacing, which are verified in the well-designed Z-shaped channels. The proposed heterostructure system can be used to design multi-band multi-functional high-flexibility topological devices, providing great advantages for enlarging the on-chip integrated communication systems.


Repetitive Transcranial Magnetic Stimulation Changes Cerebral Oxygenation on the Left Dorsolateral Prefrontal Cortex in Bulimia Nervosa: A Near-Infrared Spectroscopy Pilot Study.
Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN.


A radiographic technique for maxillary third molars.
To obtain an accurate radiographic image of the maxillary third molars with roots and without the superimposition of the zygomatic arch is sometimes difficult. A simple, fast, and effective technique to obtain such an image is described. The technique could be useful also in the practice for handicapped patients as it requires little cooperation from the patient.


A "Code ICU" expedited review of critically ill patients is associated with reduced emergency department length of stay and duration of mechanical ventilation.
To examine the effect of a system of expedited review of critically ill patients in the Emergency Department (ED) on ED length of stay (LOS) and Intensive Care Unit (ICU) outcomes. Retrospective cohort study at a tertiary hospital comparing two 12-month periods before and after implementation of a 'Code ICU' system of expedited review of critically ill patients in the ED. All adult ED to ICU admissions were included. Separate analyses were performed for patients intubated prior to ICU admission. 622 and 629 patients were included in each time period. During the intervention period more patients had ED LOS<240min in both the total [199 (32.0%) vs. 243 (38.6%), P=0.014; adjusted OR 1.60, 95% CI 1.14-2.25] and intubated cohorts [145 (51.2%) vs. 172 (61.9%), P=0.011; adjusted OR 1.65, 95% CI 1.16-2.36]. 'Code ICU' intubated patients had a shorter duration of mechanical ventilation, ICU LOS and hospital LOS compared to non-'Code ICU' intubated patients. A system of rapid review of critically ill patients in the ED was associated with reduced ED LOS and improved ICU outcomes.


[Studies of phosphorylation in rat mast cells (supplement 2). Diphosphoinositide kinase in rat mast cell granules].
Rat mast cells were purified by a Percoll gradient, and the granules were isolated from the sonicated mast cells on a Percoll gradient. The granules were shown to contain a diphosphoinositide kinase which catalyzes the formation of triphosphoinositide (TPI) from diphosphoinositide (DPI). The enzyme requires ATP and Mg2+ for the activity. TPI formation is almost completely dependent on MgCl2 or MnCl2, and maximal response is observed at 20 mM or 1 mM, respectively. The Km for ATP is 3 microM. TPI formation in the granules is dependent on the reaction time. The maximal response is seen at 23 degrees C. NaCl, KCl, Na2HPO4 and KH2PO4 have no effect on the activity. One hundred microM adenosine, AMP, ADP, and 10 microM cyclic AMP inhibit the kinase activity.


Effects of gender on the number of diseased vessels and clinical outcome in Japanese patients with acute coronary syndrome.
It has been reported that women with acute myocardial infarction (AMI) have a higher short-term mortality rate than men, but the reason is unclear and it is not known if it also applies to unstable angina pectoris (UAP). In addition, most previous studies have not presented angiographic findings. In the present study, the findings from 1,408 patients with AMI (group A: 361 women, 1,047 men) and 332 patients with UAP (group B: 103 women, 229 men) who underwent coronary angiography within 30 days of onset were analyzed. In both groups, the women were older and had a higher rate of hypertension and a lower rate of smoking than the men. There was no significant difference in Killip class or the number of diseased vessels between the women and men in both groups. Interventions (coronary angioplasty and coronary artery bypass grafting) were performed less frequently in the women than in the men (87.2% vs 91.8%, p=0.04) in group A, but not in group B (80.6% vs 81.2%, NS). In both groups, the overall mortality rate during hospitalization was higher in women than in men (group A: 14.4% vs 7.4%, p<0.0001, group B: 7.8% vs 1.7%, p=0.007). Multivariate analysis revealed that female gender was an independent predictor of in-hospital mortality in group B (odds ratio (OR): 6.4, 95% confidence interval (CI) 1.1-37.0, p=0.04), but not in group A (OR: 1.7, 95%CI 0.98-2.9, p=0.06). The independent predictors of in-hospital mortality, other than female gender were age, prior congestive heart failure, prior cerebrovascular disease and a higher Killip class in group A, and in both groups a higher number of diseased vessels. In conclusion, Japanese women with acute coronary syndromes present with similar angiographic findings and hemodynamics, but have a higher in-hospital mortality than male patients. Our results suggest that older age may be a potential explanation for the higher in-hospital mortality in women with AMI, but female gender itself may be an important predictor for it among those with UAP.


Pituitary metastasis mimicking a macroadenoma from carcinoma of the larynx: a case report.
Metastatic tumors of the pituitary gland are not commonly diagnosed during life in cancer patients. The occurrence of symptomatic lesions is also very unusual and difficult to differentiate clinically and radiologically from pituitary adenomas. Furthermore, a single intrasellar metastasis from laryngeal carcinoma mimicking a pituitary adenoma is an extremely rare pathological finding. We report on the clinical, radiological, and pathological findings in a patient with laryngeal carcinoma who had a symptomatic solitary pituitary gland metastasis that was recognized antemortem.


Short-term effects of chlorotriazines on estrus in female Sprague-Dawley and Fischer 344 rats.
Atrazine or simazine (s-chlorotriazines) was administered by gavage daily for 2 wk to female Sprague-Dawley and Fischer 344 rats at oral doses of 100 or 300 mg/kg to evaluate effects on body, ovary, uterus, and adrenal weights, estrous cycle stages, vaginal cytology, and plasma hormone (estradiol, progesterone, prolactin, and corticosterone) levels. Significant reductions in body weights of both Sprague-Dawley and Fischer 344 female rats at both dose levels were accompanied by a significant reduction in ovarian and uterine weights, and a decrease in circulating estradiol levels. The magnitudes of the effects were less in Fischer 344 rats than in Sprague-Dawley rats, and the effects of simazine were less pronounced than those of atrazine at the same dose. A maximum tolerated dose (MTD: > or = 10% body weight reduction) was estimated to be 100 mg/kg for atrazine and 300 mg/kg for simazine for both stains. The Sprague-Dawley female rats exhibited a treatment-related lengthening of the estrous cycle and an increased number of days characterized by cornified epithelial cells. This resulted in a greater percent of the cycle days spent in estrus and reduction in the percent of the cycle days spent in diestrus. Atrazine-dosed Fischer 344 females also exhibited a significant trend toward cycle lengthening, but this was due to reduction in the percent of cycle spent in estrus and a concomitant increase in diestrual days. These findings suggest that treatment with doses of triazine at or above the MTD may result in prolonged exposure to endogenous estrogen in the Sprague-Dawley but not the Fischer 344 rat. These changes may account for the observed earlier onset and/or increased incidence of mammary tumors in chlorotriazine-treated female Sprague-Dawley rats. This strain of rat is already known to be prone to a substantial development of mammary tumors with advancing age, while the Fischer 344 strain is not as likely to exhibit this response.


Investigation of xylanase, diet formulation method for energy, and choice of digestibility index marker on nutrient and energy utilization for broiler chickens and pigs.
The aim of this study was to investigate the growth performance and nutrient utilization responses of broiler chickens and the nutrient utilization of pigs to xylanase, experimental diet formulation method for energy (FME), and digestibility index marker (DIM). In Exp. 1, a total of 448 male broiler chickens were used in a randomized complete block design with body weight (BW) as a blocking factor. Seven dietary treatments were prepared in a 3 × 2 + 1 factorial arrangement with inclusion of sand, diatomaceous earth (DAE), or wheat bran (WB) as FME and without or with xylanase (26,400 units/kg of diet) plus positive control. Each of chromic oxide and titanium dioxide was incorporated at 5 g/kg in diets. There were eight replicate cages of eight birds per cage. Birds were weighed on d 7, 14, and 21, and feed intake was recorded. Excreta samples were collected from d 19 to 21. On d 21, birds were euthanized, and ileal digesta samples were collected. In Exp. 2, twenty-one barrows (initial BW = 33.0 ± 0.3 kg), fitted with simple T-cannulas at the distal ileum, were used in a triplicate 7 × 2 incomplete Latin Square design with seven dietary treatments, which were prepared by the same arrangement as in broiler chickens, and two periods giving six replicates per diet. Fecal samples were collected on d 4 and 5, and ileal digesta samples were collected on d 6 and 7 of each period. In Exp. 1, the growth performance of birds was not affected by xylanase. There were interactions (P < 0.05) between xylanase and FME for apparent ileal digestibility (AID) of crude protein, His, Met, Thr, and Trp. Inclusion of xylanase decreased (P < 0.05) the AID of crude protein and Trp in sand diet and AID of His and Thr in DAE diet, but increased (P < 0.05) AID of Met in WB diet. The AID of energy and nutrients except Arg and Met were greater (P < 0.05) observed with Cr than Ti as DIM. In Exp. 2, there were interactions (P < 0.05) between xylanase and FME for AID of dry matter, energy, Arg, and Lys. Inclusion of xylanase decreased (P < 0.05) the AID of Lys in DAE or WB diet, but increased (P < 0.05) AID of Arg in sand diet and AID of energy in WB diet. The DIM type had no effect on responses in pigs. In conclusion, the efficacy of xylanase on ileal energy and amino acids digestibility depends on the choice of FME in broiler chickens and pigs, and DIM affects the determination of ileal digestibility in broiler chickens.


Duplex scanner study of carotid artery dissection following surgical treatment of aortic dissection type A.
In patients suffering from aortic dissection, persistent perfusion of the false lumen distal to the implanted graft is frequent. Postoperative follow-up examinations of the carotid arteries of these patients were performed by duplex scanner and correlated with clinical symptoms. Thirty-nine patients who survived the surgical treatment of acute type A aortic dissection had duplex sonography of both common carotid arteries after an average postoperative follow-up of 53 months. In 21 cases a composite graft and in 18 cases a supracoronary prosthetic vascular graft were implanted. No sign of residual dissection of the common carotid arteries was seen in 23 patients; in nine there was a dissection of both common carotid arteries, and seven patients had a unilateral carotid dissection (five right, two left). There were nine symptomatic patients with the following symptoms: transient ischemic attack (four), amaurosis fugax (four), stroke with incomplete recovery (one). Two symptomatic patients had a corresponding dissection. The generally good prognosis of all these patients suggests a conservative nonoperative treatment.


The effect of the hiv/aids epidemic on africa's truck drivers.
The AIDS epidemic is having a growing impact on the transport sector of the economy of sub-Saharan Africa, where long-distance truck drivers are at an increased risk of infection due to their frequent contacts with commercial sex workers. The spread of AIDS in the transport industry is especially significant to the economy, as truck drivers are largely responsible for transporting crops and supplies needed for daily subsistence. In this paper we analyze these effects via two models, one employing a switch and the other a Verhulst saturation function, to describe the rate at which new drivers are recruited in terms of the supply and demand for them in the general population. Results provide an estimate of the epidemic's economic impact on the transportation sector through the loss of truck drivers (an estimated 10% per year, with endemic levels near 90%).


Targeted therapy: its status and promise in selected solid tumors. Part II: Impact on selected tumor subsets, and areas of evolving integration.
This second article in our two-part series on targeted therapies in solid tumors covers the emergence of targeted therapies for the treatment of two common malignancies: lung cancer and breast cancer. In these two tumors, the identification of a promising target has led to successful preliminary applications, and eventually to further advances through drug development and the fine tuning of patient selection. As a result, the percentage of patients with breast or lung cancer who are benefiting from targeted agents has steadily increased, even if the majority are still treated with conventional cytotoxic regimens. We also review the latest therapeutic strategies for colorectal and gynecologic cancers--because these offer an instructive contrast. The curative regimens that have been developed for these two tumors--even those in more advanced stages--have included combinations of surgery and/or radiation with chemotherapy. The Cancer Genome Atlas has revealed complexities in the biology of these tumors that underscore the fact that reliance on selective DNA-damaging agents such as platinums, antimetabolites, and antimitotic agents will continue for some time. We conclude that the therapeutic progress that may arise from the study of molecular pathways will be due not only to the development of new targeted therapies, but also to a better understanding of older drugs developed empirically in the past. Taken together, these two types of advance illustrate the remarkable overall effect of modern cancer therapeutics' focus on tumor biology and tumor immunology.


Copper-Catalyzed Regio- and Stereoselective Formal Hydro(borylmethylsilyl)ation of Internal Alkynes via Alkenyl-to-Alkyl 1,4-Copper Migration.
Catalytic reactions involving 1,n-metal migration from carbon to carbon enable a nonclassical way of constructing organic molecular skeletons, rapidly providing complex molecules from relatively simple precursors. By utilization of this attractive feature, a new and efficient synthesis of alkenylsilylmethylboronates has been developed by formal hydro(borylmethylsilyl)ation of unsymmetric internal alkynes with silylboronates under copper catalysis. The reaction proceeds regioselectively and involves an unprecedented alkenyl-to-alkyl 1,4-copper migration. The reaction mechanism has been investigated by a series of kinetic, NMR, and deuterium-labeling experiments.


Electromagnon with Sensitive Terahertz Magnetochromism in a Room-Temperature Magnetoelectric Hexaferrite.
An electromagnon in the magnetoelectric (ME) hexaferrite Ba_{0.5}Sr_{2.5}Co_{2}Fe_{24}O_{41} (Co_{2}Z-type) single crystal is identified by time-domain terahertz (THz) spectroscopy. The associated THz resonance is active on the electric field (E^{ω}) of the THz light parallel to the c axis (∥ [001]), whose spectral weight develops at a markedly high temperature, coinciding with a transverse conical magnetic order below 410 K. The resonance frequency of 1.03 THz at 20 K changes -8.7% and +5.8% under external magnetic field (H) of 2 kOe along [001] and [120], respectively. A model Hamiltonian describing the conical magnetic order elucidates that the dynamical ME effect arises from antiphase motion of spins which are coupled with modulating electric dipoles through the exchange striction mechanism. Moreover, the calculated frequency shift points to the key role of the Dzyaloshinskii-Moriya interaction that is altered by static electric polarization change under different H.


Intraoperative recording of the His bundle electrogram in man. An assessment of its precision.
To estimate the effect of distance between the electrode and the signal source on the amplitude of the His bundle electrogram (HBE) recorded during open heart surgery, a specially designed probe, containing six pairs of closely spaced (1 mm) electrodes was placed on the endocardial surface of the right atrium such that each electrode pair was parallel to the course of the His bundle. The amplitude of the HBE recorded through electrodes closest to the His bundle ranged from 0.76 to 2.44 mV, at 1mm from 0.38 to 1.13 mV, at 2mm from 0.27 to 0.86 mV, and at 3 mm from 0.2 to 0.44 mV. Maximal amplitude of HBE decreased by 57% at 1mm, 73% at 2 mm, and 82% at 3mm. The percent decrease was initially rapid, then declined more slowly at distances greater than 1 mm, resembling in form data obtained previously in animal studies by different techniques. Since the maximum HBE was greater than 1.0 mV in nine of 11 patients, and equal to or greater than 1.0 mV in only two of 11 patients at 1 mm, and less than 1.0 mV in all patients 2.0 mm from the maximal HBE, the anatomic location of the His bundle can be estimated from HBE amplitude. Intracardiac electrograms, recorded through closely spaced bipolar electrodes during open heart surgery, afford clinically useful precision in locating the specialized conduction tissue of the heart.


In vivo targeting of DC-SIGN-positive antigen-presenting cells in a nonhuman primate model.
In vivo targeting of antigen-presenting cells (APCs) with antigens coupled to antibodies directed against APC-specific endocytic receptors is a simple and a promising approach to induce or modulate immune responses against those antigens. In a recent in vitro study, we have shown that targeting of APCs with an antigen coupled to an antibody directed against the endocytic receptor DC-SIGN effectively induces a specific immune response against that antigen. The aim of the present study was to determine the ability of the murine antihuman DC-SIGN antibody AZN-D1 to target APCs in a cynomolgus macaque model after its administration in vivo. Immunohistochemical analysis demonstrated that macaques injected intravenously with AZN-D1 have AZN-D1-targeted APCs in all lymph nodes (LNs) tested and in the liver. DC-SIGN-positive cells were mainly located in the medullary sinuses of the LNs and in the hepatic sinusoids in the liver. No unlabeled DC-SIGN molecules were found in the LN of AZN-D1-injected macaques. Morphologic criteria and staining of sequential LN sections with a panel of antibodies indicated that the DC-SIGN-targeted cells belong to the myeloid lineage of APCs. In conclusion, this is the first study that shows specific targeting of APCs in vivo by using antibodies directed against DC-SIGN.


Increased risk of atherosclerosis associated with pesticide exposure in rural areas in Korea.
Atherosclerosis is a progressive inflammation in systemic vessels, and pesticide exposure has been emerging as its risk factor. This cross-sectional study investigated the association between pesticide exposure and the risk of atherosclerosis in a rural population in Korea using carotid intima-media thickness (CIMT). This study used dataset from the baseline survey of the Korea Farmers Cohort Study between November 2005 and January 2008, and the final analysis included 477 participants. Well-structured questionnaires were used to estimate pesticide exposure. CIMT ≥ 0.9 mm was established for carotid atherosclerosis. Multiple logistic regression analyses were undertaken to evaluate the association between pesticide exposure and atherosclerosis, adjusting demographic and health-related confounders. Even after adjustments, the increased risk of atherosclerosis was significantly associated with pesticide exposure, such as a lifetime history of farming (odds ratio [OR] 3.25 95% confidence interval [CI] 1.51-6.98), a history of using pesticide (OR 3.42 95% CI 1.63-7.16), using pesticide 10 times or more annually (OR 2.55 95% CI 1.21-5.39), and higher cumulative exposure index level (OR 3.63 95% CI 1.65-7.97). Further prospective studies are required to elucidate effects of pesticide exposure on the risk of atherosclerosis.


The acute effects of preoperative ozone theraphy on surgical wound healing.
To investigate the effects of preoperative rectal ozone insufflation on surgical wound healing over the proinflammatory cytokines and histopathological changes. Twenty one rabbits were divided into 3 groups. Sham, surgical wound, and ozone applied (6 sessions, every other day 70 µg/mL in 12 mL O2-O3 mixture rectally) surgical wound groups were created. TNF-alpha and IL-6 levels from all rabbits were studied at the basal, 24th hour, and 72nd hour. The histopathological examination was done by removing the surgical scar tissue at the end of 72nd hour. TNF-alfa and IL-6 levels were significantly lower compared to the control group, in the rabbits treated with ozone. The increase in angiogenesis, the decrease in the number of inflammatory cells, epidermal and dermal regeneration, better collagen deposition, and increased keratinisation in stratum corneum were observed in the histopathological examination. It was determined that the wound healing noticeably accelerated in the ozone group. Preoperative rectal ozone insufflation had a positive effect on surgical wound healing in acute period.


Fermented soymilk increases voluntary wheel running activity and sexual behavior in male rats.
Wheel running by rodents is thought to reflect voluntary exercise in humans. The present study examined the effect of fermented soymilk (FSM) on voluntary wheel running in rats. FSM was prepared from soymilk (SM) using the bacteria Leuconostoc pseudomesenteroides. The rats were fed a normal diet for 3 weeks followed by a 3-week administration of diet containing FSM or SM (5% w/w), and then the diets were switched back to a normal diet for 3 weeks. The voluntary wheel running activity was increased by FSM administration, although no changes were observed by SM administration. This effect was observed 2 weeks after FSM administration and lasted 1 week after deprivation of FSM. Then we evaluated the effect of FSM on sexual behavior in male rats. FSM administration for 10 days significantly increased the number of mounts. The protein expression of tyrosine hydroxylase (TH) increased in the hippocampus by FSM administration and it is suggested that FSM may change norepinephrine or dopamine signaling in the brain. Our study provides the first evidence that FSM increases voluntary wheel running activity and sexual behavior and suggests that TH may be involved in these effects.


Full term broad ligament pregnancy through a Cesarean scar.
A broad ligament pregnancy is an extremely rare condition. Diagnosis is often missed and finally made during laparotomy. We present a case which remained undiagnosed throughout her pregnancy till she reached term and unfortunately had intrauterine foetal demise when she reported to our hospital. On clinical suspicion, ultrasound and magnetic resonance imaging evaluation was done which picked up the diagnosis of abdominal pregnancy. On laparotomy a broad ligament pregnancy was found with a rent in the previous Cesarean scar towards the gestational sac in the broad ligament.


Expect the Unexpected: Mycobacterial Infection in Post Total Knee Arthroplasty Patients.
Orthopaedic Surgeons rarely encounter mycobacterial infections in Post Total Knee Arthroplasty (TKA) patients. We present series of two cases to create awareness among clinicians to expect the unexpected. Tuberculosis typical/ atypical is a hidden culprit in catch clinical situations when chronic infection is Suspected, but the lab investigations are negative in persistently symptomatic patients. In such situations clinicians should suspect atypical or complex mycobacterial infections and evaluate the patients accordingly. Clinical suspicion, evaluation, isolation and treatment of atypical or complex mycobacterial infections with sensitive chemotherapy, leads to complete resolution of infection and full functional rehabilitation.


Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension.
While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH.


[Left ventricular function in gated single photon emission computed tomography (GSPET) in patients with myocardial infarction subjected to thrombolysis or primary PTCA].
Primary Percutaneous Transluminal Coronary Angioplasty (PTCA) is increasingly common method of treatment patients with acute myocardial infarction. The aim of the study was to assess the left ventricular function in patients with myocardial infarction subjected to thrombolysis or primary PTCA. Gated Single Photon Emission Computed Tomography was performed in 40 patients 6 months after myocardial infarction treated either with thrombolysis or primary PTCA. Left ventricular ejection fraction (LVEF), left ventricular enddiastolic (LVED) and systolic (LVES) volumes were analysed both at rest and after stress. Six months after myocardial infarction LVEF was significantly greater and LVED, LVES volumes smaller in patients treated with primary PTCA in comparison to patients treated with thrombolysis. The above observation suggests that patients subjected to primary PTCA might have better functional outcome in comparison to matched patients treated with thrombolysis after 6 months post myocardial infarction.


Photophysical and computational investigations of bis(phosphine) organoplatinum(II) metallacycles.
A series of endohedral and exohedral amine-functionalized ligands were synthesized and used in the construction of supramolecular D(2h) rhomboids and a D(6h) hexagon. These supramolecular polygons were obtained via self-assembly of 120° dipyridyl donors with 180° or 120° diplatinum precursors when combined in 1:1 ratios. Steady-state absorption and emission spectra were collected for each ligand and metallacycle. Density functional theory (DFT) and time-dependent DFT calculations were employed to probe the nature of the observed optical transitions for the rhomboids. The emissive properties of these bis(phosphine) organoplatinum metallacycles arise from ligand-centered transitions involving π-type molecular orbitals with modest contributions from metal-based atomic orbitals. The D(2h) rhomboid self-assembled from 2,6-bis(4-pyridylethynyl)aniline and a 60° organoplatinum(II) acceptor has a low-energy excited state in the visible region and emits above 500 nm, properties which greatly differ from those of the parent 2,6-bis(4-pyridylethynyl)aniline ligand.


Apical hypertrophic cardiomyopathy associated with chronic hypertension: diagnostic and management implications.
Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM in the non-Japanese population (1% to 2%). Diagnostic dilemma occurs when this type of HCM is newly discovered in a patient previously diagnosed with left ventricular hypertrophy (LVH) secondary to hypertension. We describe an atypical presentation of an apical HCM in the setting of chronic hypertension (HTN) and review the literature of this rare variant of HCM. Our patient presented with chest pain and was found to have apical HCM with inducible apical ischemia and an abnormal blood pressure response to exercise. Multimodality imaging approach is proposed to evaluate the LVH when both apical HCM and hypertension are present given the impact of an accurate diagnosis on prognosis and management.


Long common channel syndrome as etiology of choledochal cysts and pancreatitis--two instructive cases.
The aetiology of choledochal cysts is controversial. The authors report two cases of Type I C and Type IV B choledochal cysts; both showing axial dilatation of the common bile duct and common hepatic ducts, single fusiform (Type IC) and multiple cysts of extrahepatic ducts only (Type IVB). Both had anomalous junction of the pancreaticobiliary ductal system as delineated on ERCP leading to the formation of a long common channel. Both these female patients presented in the third decade of life with 7-8 years history of repeated episodes of right upper abdominal and epigastric pain suggestive of pancreatitis. Similar pain was precipitated in both patients following ERCP with raised serum amylase. Hepatico-enterostomy gave lasting relief in both these patients.


An acoustic and articulatory study of laryngeal and place contrasts of Kalasha (Indo-Aryan, Dardic).
The Northwestern group of Indo-Aryan (Dardic) languages is generally known to have undergone consonantal shift, which resulted in the loss of voiced aspirated (VDA) stops and affricates of Sanskrit. Kalasha, an endangered Dardic language spoken in Chitral (Northern Pakistan), still preserves the Old Indo-Aryan four-way laryngeal system. The current study examines acoustic and articulatory correlates of Kalasha's four-way laryngeal contrast across places and manners of articulation, using lingual ultrasound-imaging and several acoustic measures. The analysis included the standard acoustic [voice onset time (VOT), after prevoicing interval (API), fundamental frequency onset, first four spectral moments] and articulatory (smoothing spline analysis of variance) measures, which capture laryngeal, place, and manner differences in consonants. The results showed that VOT reliably differentiated the four-way laryngeal contrast of Kalasha. VDA stops and affricates are characterized by shorter voicing lead VOT, higher API, and lower fundamental frequency onset than their voiced unaspirated (VDUA) counterparts. However, the first four spectral moments did not distinguish the two VDUA and VDA stop series. The tongue root retraction distinguishes the voiceless stops and affricates from the voiced ones.


Betrayals in Emerging Adulthood: A Developmental Perspective of Infidelity.
Infidelity is associated with considerable distress and discord in dating relationships. The current mixed methods study examined both the written narratives and survey responses of 104 (59.6% women) emerging adults to investigate reasons for engaging in infidelity (i.e., sexual and emotional infidelity). Emerging adults' reasons for engaging in infidelity were attributed primarily to their primary relationships and/or their romantic partners not fulfilling their needs for interdependence and thus feeling motivated to fulfill these needs elsewhere. Although the majority of participants provided independence and/or interdependence reasons for their infidelity, a large proportion of responses (40%) referenced alternative reasons. These responses included (a) the opportunity to become intimate with an infidelity partner while under the influence of alcohol, (b) attraction to an infidelity partner, and (c) the excitement and novelty that the infidelity experience provided. Those who reported engaging in infidelity because of unmet interdependence needs, and intimacy needs in particular, were more avoidantly attached than those who did not reference unmet interdependence needs. Those who reported engaging in infidelity because of unmet independence needs were more anxiously attached than those who did not reference unmet independence needs. Implications for the developmental importance of infidelity in terms of research and applied work are discussed.


Kidney donation after circulatory death in a country with a high number of brain dead donors: 10-year experience in Belgium.
Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its reintroduction in 2000. Risk factors for delayed graft function (DGF) were identified using multivariate analysis. Five-year patient/graft survival was assessed using Kaplan-Meier curves. The evolution of the kidney donor type and the impact of DCDs on the total KT activity in Belgium were compared with the Netherlands. Between 2000 and 2009, 287 DCD KT were performed. Primary nonfunction occurred in 1% and DGF in 31%. Five-year patient and death-censored graft survival were 93% and 95%, respectively. In multivariate analysis, cold storage (versus machine perfusion), cold ischemic time, and histidine-tryptophan-ketoglutarate solution were independent risk factors for the development of DGF. Despite an increased number of DCD donations and transplantations, the total number of deceased KT did not increase significantly. This could suggest a shift from DBDs to DCDs. To increase KT activity, Belgium should further expand controlled DCD programs while simultaneously improve the identification of all potential DBDs and avoid their referral for donation as DCDs before brain death occurs. Furthermore, living donation remains underused.


Complete Genome Sequences of Lytic Bacteriophages of Xanthomonas arboricola pv. juglandis.
Three bacteriophages, f20-Xaj, f29-Xaj, and f30-Xaj, with lytic activity against Xanthomonas arboricola pv. juglandis were isolated from walnut trees (VIII Bío Bío Region, Chile). These lytic bacteriophages have double-stranded DNA (dsDNA) genomes of 43,851 bp, 41,865 bp, and 44,262 bp, respectively. These are the first described bacteriophages with lytic activity against X. arboricola pv. juglandis that can be utilized as biocontrol agents.


Disclosure of risks associated with regional anesthesia: a survey of academic regional anesthesiologists.
In view of the relatively few large studies available to estimate the rates of complications following regional anesthesia, we aimed to identify and quantify the risks that academic regional anesthesiologists and regional anesthesia fellows disclose to their patients before performing central and peripheral nerve blockade. We asked 23 North American regional anesthesia fellowship program directors to distribute a questionnaire to the regional anesthesiologists and regional anesthesia fellows at their institutions. The questionnaire was designed to capture the risks and corresponding incidences that are routinely disclosed to patients before performing the most common central and peripheral nerve block techniques. The total number of respondents was 79 from 12 different institutions. Fifty-eight (74%) respondents disclose risks of regional anesthesia in order to allow their patients to make an informed choice, whereas 20 (26%) disclose risks for medicolegal reasons. For central neural blockade, the most commonly disclosed risks are headache, local pain/discomfort, and infection. For peripheral nerve blockade, the most commonly disclosed risks are transient neuropathy, local pain/discomfort, and infection. For both central and peripheral nerve blockade, the risks most commonly disclosed are also those with the highest-reported incidences. The risks of regional anesthesia most commonly disclosed to patients by academic regional anesthesiologists and regional anesthesia fellows are benign in nature and occur frequently. Severe complications of regional anesthesia are far less commonly disclosed. The incidences of severe complications disclosed by academic regional anesthesiologists and their fellows can be inconsistent with those cited in the contemporary literature.


Matrix proteins of basement membrane of intrahepatic bile ducts are degraded in congenital hepatic fibrosis and Caroli's disease.
Congenital hepatic fibrosis (CHF) and Caroli's disease are though to result from ductal plate malformation, and the basal laminar components play important roles in biliary differentiation during development. To clarify the involvement of basal laminar components in the ductal plate malformation, this study examined the immunohistochemical expression of laminin and type IV collagen in the livers of CHF and Caroli's disease. Using the polycystic kidney (PCK) rat, an animal model of Caroli's disease with CHF, in vivo and in vitro experiments were also performed. Immunostaining showed that basement membrane expression of laminin and type IV collagen around intrahepatic bile ducts was degraded in CHF, Caroli's disease, and the PCK rats. The degradation of laminin and type IV collagen around bile ducts was also observed in foci of cholangiocarcinoma in situ of Caroli's disease. In vitro, PCK cholangiocytes were found to overexpress plasminogen and a serine proteinase, the tissue-type plasminogen activator (tPA). When PCK cholangiocytes were cultured in Matrigel, the amounts of laminin and collagen in the gel were significantly reduced, and addition of alpha2-antiplasmin in the culture medium inhibited the degradation of laminin and collagen in Matrigel. These results suggest that biliary overexpression of plasminogen and tPA leads to the generation of excessive amounts of plasmin, and subsequent plasmin-dependent lysis of the extracellular matrix molecules may contribute to the biliary dysgenesis in CHF and Caroli's disease, including progressive cystic dilatation of the intrahepatic bile ducts in Caroli's disease. In addition, it is suggested that once cholangiocarcinoma in situ develops in the biliary epithelium of CHF and Caroli's disease, it tends to transform into invasive carcinoma, due to instability of the basement membrane of the bile ducts.


Factors in the interictal record predicting an ictal episode: a case study.
This report deals with a patient with intractable seizures, who had 64 subdural electrodes implanted onto the left frontal and temporal cerebral cortex in anticipation of probable seizure surgery. One specific region on the left frontal lobe proved to be the focus for both the interictal spikes and also for the ictal activity. Our goal was to determine what electrical characteristics in the interictal record predicted the ictal episodes. The number of interictal spikes and also the amount of fast activity (15-128/sec) progressively increased before each of the 5 ictal episodes; an analysis showed that the number of spikes and their frequency proved the more significant variable. One other characteristic that changed before the ictal episodes was a great decrease in the interval between spikes as an example of a diminishing variability or increasing periodicity. Thus, the important factors in the interictal record that lead to an ictal event are the number of spikes, the amount of fast activity and the decreasing variability between the spikes.


Response of canine coronary collateral vessels to ergonovine and alpha-adrenergic stimulation.
The ability of moderately well-developed coronary collateral vessels to undergo vasoconstriction in response to alpha-adrenergic stimulation and to ergonovine was studied. Studies were performed in 15 dogs 4-16 wk after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. Interarterial collateral flow was measured as retrograde flow from the cannulated left anterior descending coronary artery, while microvascular collateral flow was measured as continuing tissue flow determined with radioactive microspheres administered during the retrograde flow collection. Studies were performed after beta-adrenergic blockade with propranolol. Neither cardiac sympathetic nerve stimulation nor alpha 1-adrenergic stimulation with phenylephrine caused significant change in retrograde blood flow or myocardial tissue flow. The selective alpha 2-adrenergic agonist, B-HT 933, decreased tissue flow in the collateral-dependent region but did not significantly alter retrograde flow. Although these data indicate that intramural microvascular collateral communications are capable of vasoconstriction in response to alpha 2-adrenergic stimulation, the larger interarterial collaterals are unresponsive to alpha-adrenergic influences. However, under the conditions of the experiment, adrenergic activity did not appear to influence collateral function, since neither alpha 1-adrenergic blockade with prazosin nor alpha 2-adrenergic blockade with rauwolscine altered collateral flow. Ergonovine, 0.2-0.8 microgram.kg-1.min-1, caused a 22 +/- 4% decrease in retrograde flow (P less than 0.01) but did not alter microvascular collateral flow. Thus, of the agents tested, only ergonovine caused vasoconstriction of the large interarterial coronary collateral vessels.


Biogenesis and topology of the secretory Na+-K+-2Cl- cotransporter (NKCC1) studied in intact mammalian cells.
The "secretory" Na+-K+-2Cl- cotransporter (NKCC1) is a member of a small gene family with nine homologues in vertebrates. Of these, seven are known to be electroneutral chloride transporters. These transporters play a number of important physiological roles related to salt and water homeostasis and the control of intracellular chloride levels. Hydropathy analyses suggest that all of these transporters have a similar transmembrane topology consisting of relatively large intracellular N and C termini and a central hydrophobic domain containing 12 membrane-spanning segments (MSSs). In recent experiments from our laboratory [Gerelsaikhan, T., and Turner, R. J. (2000) J. Biol. Chem. 275, 40471-40477], we employed an in vitro translation system to confirm that each of the putative MSSs of NKCC1 was capable of membrane integration in a manner consistent with a 12 MSS model. Here, we extend that work to the study of the biogenesis of NKCC1 in intact cells. We employ a truncation mutant approach that allows us to monitor this process quantitatively as successive MSSs are synthesized. While the results presented here confirm the 12 MSS model, they also indicate that the integration of NKCC1 into the membrane does not occur via a simple cotranslational process. In particular, we demonstrate that two MSSs, the second and sixth, require the presence of downstream sequence to efficiently integrate into the membrane.


Clinical Applications of Myelin Plasticity for Remyelinating Therapies in Multiple Sclerosis.
Central nervous system demyelination in multiple sclerosis (MS) and subsequent axonal degeneration represent a major cause of clinical morbidity. Learning, salient experiences, and stimulation of neuronal activity induce new myelin formation in rodents, and in animal models of demyelination, remyelination can be enhanced via experience- and activity-dependent mechanisms. Furthermore, preliminary studies in MS patients support the use of neuromodulation and rehabilitation exercises for symptomatic improvement, suggesting that these interventions may represent nonpharmacological strategies for promoting remyelination. Here, we review the literature on myelin plasticity processes and assess the potential to leverage these mechanisms to develop remyelinating therapies. ANN NEUROL 2021;90:558-567.