Differential display analysis of murine collagen-induced arthritis: cloning of the cDNA-encoding murine ATPase inhibitor.
We used the differential display technique in order to detect a new gene involved in murine type II collagen-induced arthritis (CIA). In this study, we have identified a novel gene, IF1, whose expression level is increased during the natural course of CIA. Northern blot analyses suggest that IF1 is involved in the natural course of CIA but is not involved as a trigger of CIA. IF1 is considered to be the murine ATPase inhibitor gene for several reasons. First, IF1 shows an extremely high homology to the rat ATPase inhibitor; the highly conserved region between rat and bovine amino acid residues 22-45, which is the minimum sequence showing ATPase inhibitory activities, is also highly conserved in IF1. Second, IF1 possesses a histidine-rich region in the same area, which is thought to be important for regulation of mammalian inhibitors. Third, the tissue distribution of IF1 is very suggestive. The expression of IF1 was very strong in energetic organs such as the heart, brain and kidney, and the development of arthritis requires great amounts of ATP. As arthritis develops rapidly, the cellular ATP pool may be decreased. Before the ATP pool is exhausted, the ATPase inhibitor may serve as a brake for ATP hydrolysis. If the supply of free energy can be reduced, the inflammation of arthritis may in turn be restored. Our hypothesis is that the ATPase inhibitor is involved in regulating the inflammatory responses.


Understanding Human-Computer Interactions in Restricted Clinical Environments.
Conducting research on human-computer interaction and information retrieval requires unobtrusive observations within existing network architectures. Most of the available tools are not suitable to be applied within restricted clinical systems. The specific requirements hinder analysis of the human factors in health sciences. We identified extensions for popular web browsers as a suitable way to conduct studies in highly regulated environments. Considering the specialized requirements and an adequate level of transparency for the recorded clinician, we developed an open-source Web Extension compatible with major web browsers. We identified the challenges associated with the specific tool and are preparing its use to understand clinical reasoning in personalized oncology.


Expression and retinoic acid regulation of the zebrafish nr2f orphan nuclear receptor genes.
The vertebrate nuclear receptor subfamily 2, group f (nr2f) genes encode orphan receptors that have the capacity to act as negative regulators of retinoic acid (RA) signaling. We describe embryonic and larval expression of four of the six zebrafish nr2f genes, nr2f1a, nr2f1b, nr2f2, and nr2f5. These genes show highly regulated patterns of expression within the central nervous system, including in the developing hindbrain, as well as in the mesoderm and endoderm. We also investigated the role of RA and fibroblast growth factor (Fgf) signaling in regulating early nr2f gene expression. RA is not required for nr2f expression in the hindbrain; however, exogenous RA can repress this expression. Conversely, we find that RA positively regulates nr2f1a expression in trunk endoderm and mesoderm. Fgf signaling is not required for nr2f expression onset in the hindbrain; however, it may play a role in maintaining rhombomere-specific expression. We report detailed expression analysis of four nr2f genes in all three germ layers. The onset of nr2f expression in the hindbrain does not require RA or Fgf signals. Our finding that RA positively regulates nr2f1a expression in the trunk supports the possibility that Nr2fs function in a negative feedback loop to modulate RA signaling in this region.


Analysis of the electron paramagnetic resonance spectrum of a radical intermediate in the coenzyme B(12)-dependent ethanolamine ammonia-lyase catalyzed reaction of S-2-aminopropanol.
The structure of the steady-state radical intermediate in the deamination of S-2-aminopropanol catalyzed by ethanolamine ammonia-lyase (EAL) from Salmonella typhimurium has been probed by electron paramagnetic resonance (EPR) spectroscopy using isotopically labeled forms of the substrate and of the adenosylcobalamin cofactor. Electron spin-spin coupling between the radical, centered on the carbon skeleton of the substrate, and the low-spin Co(2+) in cob(II)alamin (B(12r)) produces a dominant splitting of the EPR signals of both the radical and the Co(2+). Analysis of the exchange and dipole-dipole contributions to the spin-spin coupling indicates that the two paramagnetic centers are separated by approximately 11 A. Experiments with (13)C- and with (2)H-labeled forms of S-2-aminopropanol show that the radical is centered on C1 of the carbon skeleton of the substrate in agreement with an earlier report [Babior, B. M., Moss, T. H., Orme-Johnson, W. H., and Beinert, H., (1974) J. Biol. Chem. 249, 4537-4544]. Experiments with perdeutero-S-2-aminopropanol and [2-(15)N]-perdeutero-S-2-aminopropanol reveal a strong hyperfine splitting from the substrate nitrogen, which indicates that the radical is the initial substrate radical created by abstraction of a hydrogen atom from C1 of S-2-aminopropanol. The strong nitrogen hyperfine splitting further indicates that the amino substituent at C2 is approximately eclipsed with respect to the half-occupied p orbital at C1. Experiments with adenosylcobalamin enriched in (15)N in the dimethylbenzimidazole moiety show that the axial base of the cofactor remains attached to the Co(2+) in a functional steady-state reaction intermediate.


Role of Montmorillonite, Kaolinite, or Illite in Pyrite Flotation: Differences in Clay Behavior Based on Their Structures.
It is widely acknowledged that clay minerals have detrimental effects on the process of flotation, but the mechanisms involved are still not fully understood. In this work, the effects of montmorillonite, kaolinite, and illite on pyrite flotation were investigated from the perspective of various structures of clay minerals. Flotation tests suggested that the detrimental effect of clay minerals on the flotation of pyrite increased as follows: montmorillonite > kaolinite > illite. With the help of rheology measurements, it was found that montmorillonite significantly increased pulp viscosity, which in turn substantially reduced pyrite recovery and grade. Scanning electron microscopy (SEM) images suggested that montmorillonite formed the "house-of-cards" structure by edge-to-edge and edge-to-face contact, while kaolinite and illite platelets were associated mainly in the face-to-face mode. In addition, it was clearly observed by SEM-energy dispersive spectrometry that montmorillonite and kaolinite coat on the pyrite surfaces, which would lower the surface hydrophobicity of pyrite. Kaolinite covered much larger area of pyrite surface than montmorillonite owing to the positive charge occurring at the exposed aluminum-oxygen octahedral sheet of kaolinite. Although illite has a similar 2:1 structure to montmorillonite, it showed little or no effect on pyrite flotation, which was attributed to its poor swelling nature. These findings shed light on the root cause of the adverse effect of clay minerals on pyrite flotation and are expected to provide theoretical guidance for mitigating the negative effects on flotation caused by clays.


Pathology of pediatric brain tumors.
In characterizing the pathology of brain tumors, diagnostic and prognostic immunohistochemical and molecular advances are indicated. Brain tumors are described from the perspective of pathologic type consistent with the standard World Health Organization classification as well as by neuroanatomical location with relevant differential diagnosis. Brain tumors associated with genetic syndromes are discussed.


Cytokines assay in peripheral blood and bronchoalveolar lavage in the diagnosis and staging of pulmonary granulomatous diseases.
The pulmonary granulomatous diseases may be staged using clinical examination, pulmonary function tests, 67Ga scans, chest X-rays, BAL and serum ACE levels; furthermore, these disorders are clearly associated to changes in lymphocyte subpopulations, CD4+/CD8+ ratio and surface receptors; in particular, T cell activation characterizes early alveolitis phase, while activated macrophages and related cytokines prevail in granulomata and fibrosis development. In this study, we dosed the serum and blood concentrations of IL-6 (a well-known pro-inflammatory cytokine), sIL-2R (marker of T-cell activation), TNF-alpha and IFN-gamma (associated with the granuloma development), in patients affected by active or inactive sarcoidosis, primary tuberculosis, idiopathic pulmonary fibrosis and healthy control subjects, using the ELISA method. Cytokines assay showed significant changes only in subjects with primary tuberculosis and active sarcoidosis; infact, primary tuberculosis was characterized by high values of IL-6 and IFN-gamma both in peripheral blood and in BAL, with high values of sIL-2R in BAL; patients with active sarcoidosis showed high levels of IFN-gamma and TNF-alpha both in BAL and in peripheral blood, associated to an increase of serum sIL-2R levels. Our data confirm that the compared assay of these cytokines in peripheral blood and BAL specimens, may be useful to diagnose and to assess the disease activity in pulmonary granulomatous diseases; in particular, the levels of sIL-2R are a marker of the alveolitis phase, while TNF-alpha and IL-6 levels discriminate patients with sarcoidosis or tuberculosis granulomata, respectively.


History and recent progress in piezoelectric polymers.
Electrets of carnauba wax and resin have exhibited good stability of trapped charges for nearly 50 years. Dipolar orientation and trapped charge are two mechanisms contributing to the pyro-, piezo-, and ferroelectricity of polymers. Since the 1950s, shear piezoelectricity was investigated in polymers of biological origin (such as cellulose and collagen) as well as synthetic optically active polymers (such as polyamides and polylactic acids). Since the discovery of piezoelectricity in poled polyvinylidene fluoride (PVDF) in 1969, the pyro-, piezo-, and ferroelectricity were widely investigated in a number of polar polymers, such as copolymers of vinylidene fluoride and trifluoroethylene, copolymers of vinylcyanide and vinylacetate, and nylons. Recent studies involve submicron films of aromatic and aliphatic polyureas prepared by vapor deposition polymerization in vacuum and the piezoelectricity of polyurethane produced by the coupling of electrostriction and bias electric fields. Gramophone pickups using a piece of bone or tendon were demonstrated in 1959. Microphones using a stretched film of polymethyl glutamate were reported in 1968. Ultrasonic transducers using elongated and poled films of PVDF were demonstrated in 1972. Headphones and tweeters using PVDF were marketed in 1975. Hydrophones and various electromechanical devices utilizing PVDP and its copolymers have been developed during the past 30 years. This paper briefly reviews the history and recent progress in piezoelectric polymers.


Metabolic regulation rather than de novo enzyme synthesis dominates the osmo-adaptation of yeast.
Intracellular accumulation of glycerol is essential for yeast cells to survive hyperosmotic stress. Upon hyperosmotic stress the gene expression of enzymes in the glycerol pathway is strongly induced. Recently, however, it was shown that this gene-expression response is not essential for survival of an osmotic shock [Mettetal JT et al. (2008) Science 319: 482–484 and Westfall PJ et al. (2008) Proc Natl Acad Sci 105: 12212–12217]. Instead, pure metabolic adaptation can rescue the yeast. The existence of two alternative mechanisms urged the question which of these mechanisms dominates time-dependent adaptation of wild-type yeast to osmotic stress under physiological conditions. The regulation of the glycerol pathway was analysed in aerobic, glucose-limited cultures upon addition of 1 M of sorbitol, leading to a hyperosmotic shock. In agreement with earlier studies, the mRNA levels of the glycerol-producing enzymes as well as their catalytic capacities increased. Qualitatively this induction followed a similar time course to the increase of the glycerol flux. However, a quantitative regulation analysis of the data revealed an initial regulation by metabolism alone. After only a few minutes gene expression came into play, but even after an hour, 80% of the increase in the glycerol flux was explained by metabolic changes in the cell, and 20% by induction of gene expression. This demonstrates that the novel metabolic mechanism is not just a secondary rescue mechanism, but the most important mechanism to regulate the glycerol flux under physiological conditions.


Biochemical Characterization of Rare and Threatened Local Populations of Peas (Pisum sativum L.) Cultivated in the Arid Region of Southern Tunisia.
Pea (Pisum sativum L.) is an important legume for human and animal consumption, cultivated in many temperate regions of the world. In the present investigation, the seeds of twelve pea accessions collected from the arid regions of southern Tunisia, characterized by different colors of flowers and seed coats, were evaluated for their proteins, phenolic compounds and antioxidant activities. The protein content determined by the Bradford method ranged from 46.91 to 151.08 mg/g DW. The content of total phenol, total flavonoid and condensed tannin, ranging from 36.85 to 102.52 mg GAE/100 g DW, 6.95 to 48.11 mg QE/100 g DW, and 12.37 to 70.43 mg CE/100 g DW, respectively. These parameters were characterized respectively by the following three methods, the Folin-Ciocalteu reagent, the aluminum chloride and the vanillin assay. The LC-ESI/MS analysis identified the presence of 8 phenolic acids and 9 flavonoids which quinic acid, protocatechuic acid, hyperoside, and quercetin-3-O-rhamnosidewere detected as the most abundant compounds. Moreover, the antioxidant activity of pea seeds was evaluated by the ABTS+and DPPH tests. Indeed, DPPH and ABTS anti-free radical activity values ranged from 1.92 to 14.11 μmoL TEAC/g DW and 2.3 to 14.95 μmoL TEAC/g DW, respectively. The variability across the assessed traits revealed significant differences as computed by ANOVA tests. Else, the results showed significant correlations between seed coat color, seed shape, flower color and phenolic compounds. Therefore, genotypes characterized by a purple flower, brown seed coat, and wrinkled form had the highest levels of phenolic compounds and antioxidant activity. Correlation analysis revealed that phenolic compounds presented a strong positive correlation with antioxidant activities, while being negatively correlated with protein content. UPGMA cluster and Principal component analysis (PCA) revealed two main groups. This work highlights the nutritional value of P. sativum seeds as a good source of natural antioxidant compounds that may be useful in the food and pharmaceutical industries.


Joint estimation of forward and backward motion vectors for interpolative prediction of video.
A low-complexity iterative algorithm is introduced for joint estimation of forward and backward motion vectors in interpolative prediction of video. Starting from the initial values obtained by a commonly-used block matching independent search method, the motion vectors are iteratively refined until a locally optimal solution to the motion estimation problem for interpolative prediction is achieved. Each iteration consists of a series of two similar procedures. First, the backward motion vector is fixed and a new forward motion vector is searched to minimize the interpolation error. Then the forward motion vector is fixed and the backward motion vector is similarly refined by minimizing the interpolation error. This process is repeated until the interpolation error stops decreasing. Computer simulation results demonstrate that with this technique the prediction error in some scenes is significantly reduced.


A method for T1 rho imaging.
The spin lattice relaxation time (T1) is dependent on the strength of the polarizing magnetic field. The relaxation at low field strengths provides information from the processes at macromolecular level. However, the decrease of the polarizing magnetic field decreases the signal-to-noise ratio that determines the resolution of magnetic resonance images. In this report we describe a method for T1 rho imaging. The method possesses the relaxation time contrast of low field strengths with signal-to-noise ratio provided by the higher polarizing field. The relaxation time T1 rho is obtained under spin lock conditions. The spin system relaxes toward thermal equilibrium along the locking field. This process is analogous to the spin lattice relaxation at low field strength and characterized by the time constant T1 rho. T1 rho and T1 rho-dispersion may provide new imaging parameters for noninvasive tissue characterization.


A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.
When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)


Behavioral effects of a deletion in Kcnn2, the gene encoding the SK2 subunit of small-conductance Ca2+-activated K+ channels.
Small-conductance Ca(2+)-activated potassium (SK) channels are heteromeric complexes of SK alpha-subunits and calmodulin that modulate membrane excitability, are responsible for part of the after-hyperpolarization (AHP) following action potentials, and thus control the firing patterns and excitability of most central neurons. An engineered knockout allele for the SK2 subunit has previously been reported. The hippocampal neurons of these mice lacked the medium latency component of the AHP, but the animals were not described as presenting any overt behavioral phenotype. In this report, we describe a deletion in the 5' region of the Kcnn2 gene encoding the SK2 subunit in the mouse neurological frissonnant (fri) mutant. The frissonnant mutant phenotype is characterized by constant rapid tremor and locomotor instability. It has been suggested, based merely on its phenotype, as a potential model for human Parkinson disease. We used a positional cloning strategy to identify the mutation underlying the frissonnant phenotype. We narrowed the genetic disease interval and identified a 3,441-bp deletion in the Kcnn2 gene, one of the three candidate genes present in the interval. Expression studies showed complete absence of normal Kcnn2 transcripts while some tissue-specific abnormal truncated variants were detected. Intracellular electrophysiological recordings of central vestibular neurons revealed permanent alterations of the AHP and firing behavior that might cause the tremor and associated locomotor deficits. Thus, the fri mutation suggests a new, potentially important physiological role, which had not been described, for the SK2 subunit of small-conductance Ca(2+)-activated potassium channels.


Evaluation of pain perception during orthodontic debonding of metallic brackets with four different techniques.
The aim of this study was to evaluate patients' pain levels during four different debonding procedures. The null hypothesis was that the pain perception of the patients undergoing four different debonding applications was not statistically significant different. One hundred and twenty orthodontic patients who underwent orthodontic debonding were included in this study. The patients were randomly divided into 4 groups according to technique used in the patients. Debonding groups were as follows: Group 1) Conventional debonding group, Group 2) Medication group (acetaminophen was given 1 hour before debonding), Group 3) Soft bite wax group, and Group 4) Soft acrylic bite wafer group. The patients' levels of anxiety and fear of pain were evaluated before debonding, and Numerical Rating Scale (NRS) was applied to evaluate their pain perception during debonding. Mann-Whitney U and Kruskal-Wallis tests were used to evaluate non-normally distributed data. Categorical data analysis were carried by chi-square and McNemar tests. The significance level was set at p<0.05. Anxiety scores of the patients were not statistically significant between both genders and debonding groups. In the quadrants in which the patients were perceived, the highest pain level was in the left side of the mandible. The teeth in which the highest pain level was perceived were the lower left and upper right lateral incisors. Although there was no statistically significant difference among the pain scores of the patients in each group, quadrant scores of female patients showed significant differences, being the lowest scores in the soft bite wax group. Majority of the patients had no fear of pain before debonding. Pain levels of the patients in the conventional debonding group were not significantly different from those of the other groups, except quadrant scores of females in the soft bite wax group. The null hypothesis was accepted.


Neuroendocrine evaluation of central opiate activity in primary headache disorders.
The evaluation of central opiate activity could be of clinical value in the diagnosis and treatment of pain syndromes. The current approach via direct measurement of endogenous opioid peptides in cerebrospinal fluid (CSF) is not devoid of side effects and cannot be used in every-day practice. As an alternative to this method, we have studied the neuroendocrine response of plasma LH to an i.v. naloxone injection in 39 headache sufferers from different diagnostic subgroups, and in 12 age- and sex-matched healthy volunteers. Patients (19 females and 20 males) were affected by common migraine (CM, 11 cases), migraine with interparoxysmal headache (MIH, 9), classical migraine (CIM, 9), and chronic cluster headache (CH, 10). Headache lasted 3-36 years. Prior to naloxone challenge (4 mg i.v.), LH pulsatility was evaluated for 1 h. The next morning, the pituitary response to LH-RH (10 micrograms i.v.) was tested in 20 patients. Plasma LH was measured by RIA in every sample. The response to the tests was evaluated as secretion area of plasma LH minus the mean basal value. Controls (497.5 +/- 85.5 mIU/ml x 120 min), ClM (357.8 +/- 78.9) and CH (450.5 +/- 70.4) patients showed similar results, while in cases of CM (155.3 +/- 71.7, P less than 0.05) and MIH (104.1 +/- 53.7, P less than 0.01) the LH secretion after naloxone injection was significantly blunted. On the contrary, the response of LH to LH-RH was similar in controls and patient groups, thus excluding pituitary dysfunctions in this response.(ABSTRACT TRUNCATED AT 250 WORDS)


You are not what you eat during physiological stress: Isotopic evaluation of human hair.
Variation in δ(13) C and δ(15) N values can be assessed to understand not only diet, but also the influence of physiological factors on an individual. The metabolic balance of an individual can impact isotopic signals in tissues that are forming during the periods of metabolic stress. Fluctuating δ(15) N values are associated with physiological stressors that alter an individual's metabolism such as infection, injury, or pregnancy. This study examines variation in δ(13) C and δ(15) N values along sequentially segmented hair in both modern and archaeological individuals. Subjects with an observable skeletal pathology, known chronic illness, or evidence of pregnancy were compared with controls exhibiting no evidence of physiological stress. The results on hair samples from individuals from 19(th) century Belleville, Ontario, four modern cadavers (two with cancer and two sudden deaths), and two living pregnant women indicate that δ(15) N values are approximately 1‰ higher in individuals with a pathological condition (e.g., infection, fracture, or cancer) and are 1‰ lower during pregnancy, whereas δ(13) C values show less variability. Higher nitrogen values may represent the recycling of nitrogen derived from the breakdown of existing proteins in the body (catabolism), whereas lower δ(15) N values are related to increased utilization of dietary and urea nitrogen for tissue synthesis during pregnancy. These findings suggest that short-term fluctuations of δ(15) N values may be the result of changes in an individual's metabolic balance, and that metabolic imbalance poses a confounding factor to ancient dietary studies when using rapidly growing tissues such as hair.


Growth and storage processes in aerobic granules grown on soybean wastewater.
Aerobic granules in a sequencing batch reactor (SBR) are subjected to alternative feast and famine conditions, and are able to take up carbon substrate in wastewater rapidly and to store it as intracellular storage products when the substrate is in excess. This phenomenon could not be described by the widely used activated sludge model No.3 (ASM3). In this work, taking adsorption process, microbial maintenance, and substrate diffusion into account, the simultaneous growth and storage processes occurring in an aerobic-granule-based SBR are investigated with experimental and modeling approaches. A new model is established and successfully validated with the experimental results of an SBR fed with soybean-processing wastewater. Simulation results show that our approach is appropriate for elucidating the fates of major model components. Comparison between ASM3 and the model established in this work demonstrates that the latter is better to describe the substrate removal mechanisms and simultaneous growth and storage processes in aerobic granules.


Applications of biomarkers of exposure and biological effects in users of new generation tobacco and nicotine products: Tentative proposals.
Despite efforts to eliminate smoking, more than 1 billion people worldwide continue to use combustible cigarettes through choice or inability to quit. With an associated 8 million deaths, the provision of noncombustible tobacco and nicotine products that smokers will accept to replace combustible cigarettes can lessen harm. However, most of these products have entered the market only in the past 20 years. Therefore, particularly for some smoking-related diseases, epidemiological studies to test harm reduction potential are only now becoming feasible. For cancer and chronic obstructive pulmonary disease, around two decades of data might be required. In this article, we discuss how the use of biomarkers might be applied to supplement epidemiological research for regulators. We further discuss how health providers and insurers can keep up with the rapid changes in biomarker research and recognize these reduced risks.


Predictors of clinical and structural outcomes after surgery for spinal nerve sheath tumor resection: a retrospective analysis.
Resection of spinal nerve sheath tumors (SNSTs) typically necessitates laminectomy, often with facetectomy, for adequate exposure of tumor. While removal of bone affords a greater operative window and extent of resection, it places the patient at greater risk for spinal instability. Although studies have identified risk factors for fusion at the time of tumor resection, there has yet to be a study assessing long-term stability following SNST resection. In this study, the authors sought to identify preoperative and operative risk factors that predispose to long-term spinal instability and investigate clinical variables associated with greater risk for subsequent fusion in the time following initial SNST resection. An institutional registry of spinal surgeries was queried at a single institution over a 20-year period. Demographic, clinical, and operative variables were recorded retrospectively and investigated for predictive value of several postoperative sequelae. A total of 122 SNST cases among 112 patients were included. At a mean follow-up time of 27.7 months, patients with a history of neurofibromatosis type 2 (NF2) (p = 0.014) and those who had undergone a laminectomy of ≥ 4 levels at the time of initial SNST resection (p = 0.028) were more likely to present with some degree of structural abnormality or neurological deficit following their initial surgery. The presence of facetectomy, degree of laminectomy, and level of spinal surgery were not found to be predictors of future instability. Ultimately, there was no significant predictor for true spinal instability following index surgery without fusion. A secondary analysis showed that an entirely extradural location (p = 0.044) and facetectomy at index surgery (p = 0.012) were predictive of fusion being performed at the time of tumor resection. Four of the 112 patients required fusion after their index SNST resection, 3 of whom underwent fusion for instability at the level of the index surgery. No variables were identified as predictive for future instrumentation. Ultimately, the authors conclude that resection of SNSTs does not always necessitate fusion, and good outcomes can be obtained with motion-preserving techniques and minimizing facetectomy when possible. Patients with a history of NF2 and those with SNSTs that required ≥ 4-level laminectomy were more likely to exhibit some degree of structural abnormality and/or neurological deficit localized to the index level defined as either new or worsening spinal instability and/or new or worsening neurological deficit at last follow-up; however, no variable was found to be predictive of true spinal instability. Furthermore, a complete facetectomy at initial SNST resection and entirely extradural tumor location were noted to be associated with fusion at index surgery. Lastly, the authors were unable to identify a clinical predictor for future instrumentation.


Adipose-specific overexpression of GLUT-4 in transgenic mice alters lipoprotein lipase activity.
Transgenic mice overexpressing GLUT-4 selectively in adipose tissue using the aP2 promoter/enhancer develop obesity, enhanced glucose tolerance, and increased insulin sensitivity. The current study was designed to determine whether altering glucose transport affects lipoprotein lipase (LPL) activity. Female transgenic mice (10-12 mo old) have increased parametrial fat pad weight, adipocyte size, total body lipid and fasting plasma triglycerides, fatty acids, and glycerol compared with nontransgenics. Stimulation of LPL activity by feeding is blunted in parametrial and perirenal fat from 15- and 22-fold in nontransgenic mice to three- to sevenfold in transgenics. LPL activity in the fed state in transgenic mice is reduced 60-75% in fat. In heart and skeletal muscle of transgenic mice, LPL activity in the fasted state is 55-65% lower than in nontransgenics and feeding induces an unexpected rise in LPL activity. Muscle LPL activity is strongly and inversely correlated with glucose transport in adipocytes (r = -0.942, P < 0.005), which is increased 15- to 27-fold in the basal state and 4.5- to 6.9-fold in the insulin-stimulated state in transgenics. Whereas stimulation of adipose LPL may be blunted by lower plasma insulin levels in transgenics, fasting muscle LPL may be suppressed by elevated plasma lipids. Thus altering the partitioning of glucose between adipose tissue and muscle alters a critical step for the partitioning of lipoprotein fatty acids between these tissues.


Expression pattern of Dkk-1 during mouse limb development.
dkk-1 has recently been identified as a secreted protein in Xenopus laevis which is sufficient and necessary to cause head induction by antagonizing Wnt signalling (Glinka et al., 1998, Nature 391, 357-362). Consistent with such a role dkk-1 is expressed in the Spemann organizer of the early frog gastrula. Later, expression can be observed in an endomesodermal domain corresponding to the prospective prechordal plate, in two longitudinal stripes flanking the anterior chordamesoderm and in the precursors of the liver. At late neurula stage expression occurs in the prechordal plate adjacent to the prospective forebrain and eyes and in a stripe corresponding to the forming somites. dkk-1 is part of a gene family with at least three family members which is conserved between species. Its mouse homologue, Dkk-1, is first expressed at embryonic day (E) 6.5 in mesodermal cells adjacent to the embryonic/extraembryonic junction. Starting at E7.5 transcripts can be detected in the head mesoderm and at E8.5 additionally in developing somites (Glinka et al., 1998, Nature 391, 357-362). In this study we focus on the highly dynamic pattern of Dkk-1 mRNA distribution during mouse limb development from E9.0-E14.5. The other currently known family members, Dkk-2 and -3, are not expressed in the limb bud before E11.5 (C. Niehrs, pers. commun.) while the limb pattern is established. We show that Dkk-1 expression starts with the first sign of forelimb budding, whereas in the presumptive hindlimb region transcription becomes already apparent before the limb starts to bud out. Expression then becomes confined to two mesenchymal domains at E10.5 and E11.5. Using double-whole mount in situ hybridization we show that the posterior Dkk-1 expression domain initially overlaps with that of Shh, one of the key signalling molecules in limb development. Later, the two expression domains become separated. At E12.5-E14.5 Dkk-1 transcripts are restricted to the interdigital mesenchyme.


INJURIES IN AUSTRALIAN RULES FOOTBALL: A Review of the Literature.
Background: Australian Rules Football is one of the most popular sports in Australia. Successful injury prevention relies on injury surveillance to establish the extent of injuries, to monitor injury patterns and to evaluate prevention strategies. Despite the popularity of participation at the community level, few injury surveillance studies have been published, so a detailed review of the literature is vital. There is limited information available outside of the elite level. Injury statistics for any professional sport may not necessarily be translatable to community sport level.Objective: To document the most prevalent injuries at the elite, junior elite, amateur and junior level and determine if incidences differ across levels of play. Aetiology and significant risk factors for injuries are emphasized and prevention and treatment discussed.Discussion: Injuries on average are more common at the elite level compared with other levels of participation. The type of injury varies slightly, with non contact injuries, particularly muscle strains, being the most common. Of these, the hamstring strain is the most common. Aetiology and risk factors vary between levels of play due to a time basis, physical development, speed of play and skill level. Recurrence rates are a concern for clubs and players, although rates are decreasing at the elite level, indicating better treatment and conservative management of injured players.


Matrix-assisted refolding of single-chain Fv- cellulose binding domain fusion proteins.
We describe a method for the isolation of recombinant single-chain antibodies in a biologically active form. The single-chain antibodies are fused to a cellulose binding domain as a single-chain protein that accumulates as insoluble inclusion bodies upon expression in Escherichia coli. The inclusion bodies are then solubilized and denatured by an appropriate chaotropic solvent, then reversibly immobilized onto a cellulose matrix via specific interaction of the matrix with the cellulose binding domain (CBD) moiety. The efficient immobilization that minimizes the contact between folding protein molecules, thus preventing their aggregation, is facilitated by the robustness of the Clostridium thermocellum CBD we use. This CBD is unique in retaining its specific cellulose binding capability when solubilized in up to 6 M urea, while the proteins fused to it are fully denatured. Refolding of the fusion proteins is induced by reducing with time the concentration of the denaturing solvent while in contact with the cellulose matrix. The refolded single-chain antibodies in their native state are then recovered by releasing them from the cellulose matrix in high yield of 60% or better, which is threefold or higher than the yield obtained by using published refolding protocols to recover the same scFvs. The described method should have general applicability for the production of many protein-CBD fusions in which the fusion partner is insoluble upon expression.


A Comparison of the Impact of Restrictive Diets on the Gastrointestinal Tract of Mice.
The rate of gut inflammatory diseases is growing in modern society. Previously, we showed that caloric restriction (CR) shapes gut microbiota composition and diminishes the expression of inflammatory factors along the gastrointestinal (GI) tract. The current project aimed to assess whether prominent dietary restrictive approaches, including intermittent fasting (IF), fasting-mimicking diet (FMD), and ketogenic diet (KD) have a similar effect as CR. We sought to verify which of the restrictive dietary approaches is the most potent and if the molecular pathways responsible for the impact of the diets overlap. We characterized the impact of the diets in the context of several dietary restriction-related parameters, including immune status in the GI tract; microbiota and its metabolites; bile acids (BAs); gut morphology; as well as autophagy-, mitochondria-, and energy restriction-related parameters. The effects of the various diets are very similar, particularly between CR, IF, and FMD. The occurrence of a 50 kDa truncated form of occludin, the composition of the microbiota, and BAs distinguished KD from the other diets. Based on the results, we were able to provide a comprehensive picture of the impact of restrictive diets on the gut, indicating that restrictive protocols aimed at improving gut health may be interchangeable.


Cutaneous angiosarcoma clinically presenting as progressive solid facial edema in a 43-year-old male.
Cutaneous angiosarcoma of the head and neck is a rare, highly malignant neoplasm; prognosis is heavily influenced by tumor size, resectability, and stage at initial diagnosis. Most patients present with one to several erythematous to violaceous patches, plaques, or nodules. However, the clinical presentation is highly variable and leads to delayed diagnosis. We report cutaneous angiosarcoma in a 43-year-old man who presented with an 11-month history of progressive solid (non-pitting) edema involving his entire face, scalp, eyelids, and neck without characteristic clinical features of cutaneous angiosarcoma. A skin biopsy had shown non-specific findings consistent with solid facial edema or rosacea. Various etiologies were considered but there was no significant improvement after directed medical therapy. Repeat skin biopsies revealed angiosarcoma involving the dermis and sub-cutis. Computed tomography (CT) of the chest showed multiple lung nodules bilaterally and a lytic lesion in the T6 vertebra consistent with metastases. He was treated with single agent chemotherapy (paclitaxel), and had a partial response that restored his ability to open both eyes spontaneously; However, his edema has recently progressed 7 months after diagnosis. This is a rare example of cutaneous angiosarcoma presenting as progressive solid facial edema, which underscores the diverse range of clinical manifestations associated with this neoplasm.


Deriving statistical models for predicting peptide tandem MS product ion intensities.
Improved search algorithms and scoring functions are required before the identification of peptide tandem MS data can be considered to be fully reliable and automatable. The development of models that can accurately predict product ion spectra from a peptide sequence would certainly help achieve this goal, but this firstly requires a better understanding of the process of fragmentation of peptides in the gas-phase. We summarize recent developments in this area and show that the prediction of product ion spectra is feasible and should improve the identification of peptide tandem MS data, especially for peptides that currently give low or insignificant scores with current search algorithms.


Effect of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) administration of growth of Ehrlich tumor cells.
Effect of the administration of 4-hydroxypyrazolo([3,4-d]pyrimidine (allopurinol) on the growth of Ehrlich ascites tumor cells was investigated in an in vivo system. Oral administration of allopurinol (0.1% in diet) suppressed the growth of both ascites and solid types of the tumor after the implantation of Ehrlich tumor cells in mice. The inhibitory action depended on the dose but was lost repidly when the administration was interrupted. Possible mechanisms involved in the inhibitory effect of allopurinol on tumor growth were briefly discussed.


Daphnia's dilemma: adjustment of carbon budgets in the face of food and cholesterol limitation.
We studied the carbon (C) metabolism in Daphnia when the amount of C (food quantity) and/or the content of biochemical nutrients (food quality) was limiting. Growth performances and C budgets of Daphnia magna (assimilation, faeces egestion, excretion and respiration measured by [(14)C]-tracing) were analysed when animals were raised on different food quantities and concentrations of cholesterol, an essential biochemical food compound. Cholesterol is of special interest because it not only acts as limiting nutrient but also contributes to the overall C pool of the animals. As the tissue cholesterol concentration in Daphnia is quite low, we hypothesized the selective exclusion of cholesterol from C budgeting and tested this using radiolabelled cholesterol. Somatic growth rates of D. magna were highest at high quantity and quality and were reduced to a moderate value if either the food quantity or the cholesterol concentration was low. Growth was lowest at low food quantity and quality. The measurements of C budgets revealed high regulative response to low food quality at high food quantity only. Here, low dietary cholesterol caused bulk C assimilation efficiency (AE) to decrease and assimilated (excess) C to be increasingly respired. Additionally, Daphnia enhanced efficient adjustment of C budgets when facing cholesterol limitation by (1) increasing the AE of the cholesterol itself and (2) not changing cholesterol respiration, which was still not detectable. In contrast, at low food quantity, Daphnia is unable to adjust for low food quality, emphasizing that food limitation could overrule food quality effects.


Pharmacokinetic and bacteriological correlations between antimicrobial therapy of experimental meningitis in rabbits and meningitis in humans: a review.
Animal models of bacterial meningitis have been developed to study antimicrobial pharmacokinetics and efficacy for eliminating bacteria from cerebrospinal fluid (CSF) and to study pathophysiology. The correlation between observations in the rabbit model and in paediatric patients with meningitis was evaluated. When dosages of the beta-lactam or aminoglycosidic antibiotics which will produce serum concentrations approximating those in the human were given to rabbits, the degree of penetration of antibiotics into CSF and the bactericidal activity in CSF were comparable in rabbits and humans. Differing rates of elimination of Gram-negative enteric bacteria from rabbit CSF correlated directly with the bactericidal titres. However, in children with meningitis, this correlation was not found. Instead, it appeared that there was a critical level of bactericidal activity of 1:8 at which optimal killing of bacteria occurred. Increasing the bactericidal activity beyond that point did not accelerate elimination of bacteria from CSF. It is concluded that the rabbit model of bacterial meningitis is useful for predicting pharmacokinetics and activity of new antibiotics in CSF, but not for predicting differing degrees of effectiveness among antibiotics.


Hippocampal network connections account for differences in memory performance in the middle-aged rhesus monkey.
Recent neurophysiological and functional neuroimaging studies suggest that the memory decline found with normal aging is not solely due to regional disruptions in the hippocampus, but also is brought about by alterations in the functional coupling between the hippocampus and long-distance neocortical regions. However, the anatomical basis for this functional "dyscoupling" has not been fully revealed. In this study, we applied a multimodal magnetic resonance imaging technique to noninvasively examine the large-scale anatomical and functional hippocampal network of a group of middle aged rhesus monkeys. Using diffusion spectrum imaging, we have found that monkeys with lower memory performance had weaker structural white matter connections between the hippocampus and neocortical association areas. Resting state functional imaging revealed somewhat of an opposite result. Monkeys with low memory performance displayed elevated coupling strengths in the network between the hippocampus and the neocortical areas. Taken together with recent findings, this contradictory pattern may be the result of either underlying physiological burden or abnormal neuronal decoupling due to the structural alterations, which induce a neuronal compensation mechanism for the structural loss or interference on task related neuronal activation, respectively.


Two classes of murine granulocyte progenitor cells expressed in plasma clot diffusion chamber cultures.
Two distinct classes of granulocyte progenitor cells present in normal mouse bone marrow are expressed sequentially in the vivo plasma clot diffusion chamber culture system. By several criteria, progenitor cells giving rise to granulocyte colonies on day 4 of culture (CFU-D4) are different from those giving rise to colonies on day 7 (CFU-D7). These differences include: cell cycle activity as measured by in vitro incubation with cytosine arabinoside, residual concentration in the bone marrow after in vivo treatment of donor mice with cytosine arabinoside or methotrexate, resistance to osmotic lysis, size as determined by velocity sedimentation, and the morphology of the granulocyte colonies to which these cells give rise. The CFU-D7 appears to represent an earlier progenitor cell than the CFU-D4 in the differentiation pathway of the granulocyte and is analagous in many respects to the BFU-E in the erythroid pathway.


Predicting the risk of hyperkalemia in patients with chronic kidney disease starting lisinopril.
Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians' concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia. We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 ml/min/1.73 m(2)) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value >5.5 mmol/L; or (2) diagnosis code for hyperkalemia. Cox regression synthesized a priori predictors recorded in the electronic medical record into a risk score. We followed 5171 patients and 145 experienced hyperkalemia, a 90-day risk of 2.8%. Predictors included: age, eGFR, diabetes, heart failure, potassium supplements, potassium-sparing diuretics, and a high dose for the ACE-inhibitor (lisinopril). The risk score separated high-risk patients (top quintile, observed risk of 6.9%) from low-risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed within 1% for each quintile. The risk increased gradually in relation to declining eGFR with no apparent threshold for contraindicating ACE-inhibitors. The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low-risk patients. The risk score should be validated in other populations before it is ready for use in clinical practice.


Alpha/beta hydrolase fold: an update.
The alpha/beta hydrolase superfamily has rapidly expanded in recent years and continues to do so at an expeditious pace. According to the ESTHER database (http://bioweb.ensam.inra.fr/ESTHER) 29000 papers have been published cataloguing 89 family groups, comprising a total of 15438 gene loci and 666 structures. This paper presents a snapshot of the current family taxonomy, catalytic chemistries, structural topologies and useful technologies emerging from the knowledge base at the current time.


Different effects of tianeptine pretreatment in rats exposed to acute stress and repeated severe stress.
In this study we aim to discuss the relationship between stress and learning and emotionality in an experimental model using two different stress conditions: acute stress (single restraint stress for 20 min) and repeated severe stress (6-h daily restraint for 21 days). We studied the effects of tianeptine, which has been suggested to have anxiolytic and cognition-enhancing effects under stressful conditions. After acute stress, the increase in the duration of immobility (F = 5.753 and 3.664) in the open field and holeboard tests and the decrease in rearing (F = 3.891) in the holeboard test were significant when compared to controls (P < 0.05). Results for repeated severe stress showed that in both the open field and holeboard tests the decrease in rearing (F = 4.494 and 4.530, respectively), increase in the duration of immobility (F = 6.069 and 4.742, respectively) and decrease in head dips (F = 4.938) in the holeboard test were statistically significant (P < 0.05). The group pretreated with tianeptine showed no significant difference from controls for either acute or repeated severe stress conditions. In the Morris water maze test, acute stress led to a prolongation of average escape latency, which indicated a spatial learning deficit. Treatment with tianeptine prior to acute stress prevented this spatial deficit. Repeated severe stress also led to spatial learning deficits in rats, but this deficit was not prevented by treatment with tianeptine. Our study demonstrates that pretreatment with tianeptine had different effects on stress-induced spatial learning deficits under acute and repeated stress conditions, while the effects on emotionality and anxiety-like behavior were similar. The mechanisms implicated in stress-induced emotional and memory deficits will be discussed.


Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas.
Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/ Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16-101 months.


Effect Of Bevacizumab On Growth Of Human Nasal Polyposis In Vitro; An Off-Label Use Of Anti-Angiogenic Agent For Nasal Polyposis Treatment.
Nasal polyposis (NP) is a frequent problem during adulthood. Treatment of NP is primarily based on drugs, such as oral or topical steroids and in some types, by surgery. Despite of available therapeutic options for NP, recurrence after polypectomy is found. Vascular endothelial growth factor (VEGF) is a known factor involved in NP. Bevacizumab is a monoclonal antibody, which acts against VEGF. Regarding the availability of bevacizumab and its use in ophthalmic off-label application, in this study, we hypothesized that it could be a choice of non-invasive treatment. The researchers aimed at evaluating the use of bevacizumab in vitro on the growth of NP. In this experimental study, the researchers used eight non-allergic NP tissues from patients admitted for polypectomy clinic of Imam Reza Hospital, Mashhad. Tissues were cultured in DMEM medium based on standard protocols in the presence or absence of bevacizumab (10 to 250 μM) then incubated. The mean of the responses was reported. The level of VEGF and MTT test for NP epithelial cell viability were determined for each group. Data were analyzed using the SPSS software. The researchers demonstrated that bevacizumab leads to a decrease in the level of VEGF (the most common cause of angiogenesis in NP) in media culture of NP, dose-dependently (P<0.001). The highest mean was related to the 10-μM group and the least mean was related to the 250-μM group. In MTT test after 5 days, it was shown that the percentage of viable epithelial NP cells (due to apoptosis) was decreased dose-dependently and could lead to resolving NP tissue (P<0.001), significantly. This study showed that bevacizumab could help decrease the growth of NP tissue dose-dependently in organ culture in vitro by inhibiting VEGF. It seems that bevacizumab could be a good candidate for the treatment of non-allergic NP.


Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study.
We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration. We conducted an uncontrolled, non-comparative, observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU). All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days. We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.


Initiatives to improve prescribing efficiency for drugs to treat Parkinson's disease in Croatia: influence and future directions.
Parkinson's disease (PD) is the second most common neurological disease affecting older adults. Consequently, this disease should be a focus among payers, with increasing utilization of newer premium-priced patent-protected add-on therapies to stabilize or even improve motor function over time. However, expenditure can be moderated by reforms. Consequently, there is a need to assess the influence of these reforms on the prescribing efficiency for drugs to treat PD in Croatia before proposing additional measures. Prescribing efficiency is defined as increasing the use of add-on therapies for similar expenditure. An observational retrospective study of the Croatian Institute for Health Insurance database of drugs to treat patients with PD in Croatia from 2000 to 2010 was carried out, with utilization measured in defined daily doses (defined as the average maintenance dose of a drug when used in its major indication in adults). The study years were chosen to reflect recent reforms. Only reimbursed expenditure is measured from a health insurance perspective. Utilization of drugs to treat PD increased by 218% between 2000 and 2010. Reimbursed expenditure increased by 360%, principally driven by increasing utilization of premium-priced patent-protected add-on therapies, including ropinirole and pramipexole. However, following recent reforms, reducing expenditure/defined daily dose for the different drugs, as well as overall expenditure, stabilized reimbursed expenditure between 2005 and 2010. Treatment of PD is complex, and add-on therapies are needed to improve care. Reimbursed expenditure should now fall following stabilization, despite increasing volumes, as successive add-on therapies lose their patents, further increasing prescribing efficiency.


Transcriptional regulation of esophageal, intestinal, and branchial solute transporters by salinity, growth hormone, and cortisol in Atlantic salmon.
In marine habitats, Atlantic salmon (Salmo salar) imbibe seawater (SW) to replace body water that is passively lost to the ambient environment. By desalinating consumed SW, the esophagus enables solute-linked water absorption across the intestinal epithelium. The processes underlying esophageal desalination in salmon and their hormonal regulation during smoltification and following SW exposure are unresolved. To address this, we considered whether two Na+ /H+ exchangers (Nhe2 and -3) expressed in the esophagus contribute to the uptake of Na+ from lumenal SW. There were no seasonal changes in esophageal nhe2 or -3 expression during smoltification; however, nhe3 increased following 48 h of SW exposure in May. Esophageal nhe2, -3, and growth hormone receptor b1 were elevated in smolts acclimated to SW for 2.5 weeks. Treatment with cortisol stimulated branchial Na+ /K+ -ATPase (Nka) activity, and Na+ /K+ /2Cl- cotransporter 1 (nkcc1), cystic fibrosis transmembrane regulator 1 (cftr1), and nka-α1b expression. Esophageal nhe2, but not nhe3 expression, was stimulated by cortisol. In anterior intestine, cortisol stimulated nkcc2, cftr2, and nka-α1b. Our findings indicate that salinity stimulates esophageal nhe2 and -3, and that cortisol coordinates the expression of esophageal, intestinal, and branchial solute transporters to support the SW adaptability of Atlantic salmon.


Ancient heavy transport, methods and achievements.
That more and larger stones were transported over a much longer time span in the Old than in the New World is obvious. The earlier arrival of the peoples of the Old World at the level of cultural development generally termed "civilization," accompanied as it was by a superior technology (95), goes far to account for this fact. Similarities, even identities, in techniques employed in transporting heavy stones (for example, sledge, ramps) or beliefs about stones (for example, that stones can will themelves to move or remain fixed) are taken to be fortuitous and independent convergences of the same genre as those cultural parallels recently pointed out by Caso (96) and Rowe (97).


Nutrition and disease: challenges of research design.
This review discusses research methodology in the relation between diet and disease. Medical research can be divided into two types: complex research (the detailed study of disease mechanisms using such methods as biochemistry and molecular genetics) and simple research (the investigation of the factors that cause or prevent disease using methods such as epidemiology, intervention trials, and analagous studies on animals). Although complex research has received the bulk of resources, the large majority of our information of practical value has come from simple research. This general principle is illustrated in the area of diet and disease by examples from various areas: selenium, carotenoids, and cancer; vitamin E, omega-3 fatty acids, and coronary heart disease; dietary fat and obesity; dietary sodium and hypertension; and alcohol and stroke. Discussion then turns to aspects of the design of cohort (prospective) studies. Because of problems of sample size and relative lack of diversity, previous studies often failed to give clear-cut results. Suggestions are made concerning the design of cohort studies, notably the use of much larger numbers of subjects and with greater diversity in their diets. The problem of confounding also is discussed. Lifestyle factors often cluster together but cohort studies may not have fully unraveled this.


National burden estimates of hospitalisations for acute lower respiratory infections due to respiratory syncytial virus in young children in 2019 among 58 countries: a modelling study.
Respiratory syncytial virus (RSV) is the predominant viral pathogen associated with acute lower respiratory infection (ALRI) in children who are younger than 5 years. Little is reported on the national estimates of RSV-associated ALRI hospitalisations in these children on the basis of robust epidemiological data. We aimed to generate national level estimates for RSV-associated ALRI hospitalisations in children aged younger than 5 years. We included data for RSV and ALRI hospitalisation in children who were younger than 5 years from systematic literature reviews (including unpublished data) and from inpatient databases, representing 58 countries. We used two different methods, the rate-based method and the proportion-based method, to estimate national RSV-associated ALRI hospitalisations in children younger than 5 years in 2019. The rate-based method synthesised data for laboratory-confirmed RSV-associated ALRI hospitalisation rates using a spatiotemporal Gaussian process meta-regression (ST-GPR). The proportion-based method applied data for RSV positive proportions among ALRI to all-cause ALRI hospitalisation envelopes (ie, total disease burden of ALRI hospitalisations of any cause) using a Bayesian regularised trimmed meta-regression (MR-BRT). Where applicable, we reported estimates by both methods to provide a plausible range for each country. A total of 334 studies and 1985 data points (defined as an individual estimate for one age group and 1 year for each study) were included in our analysis, accounting for 398 million (59%) of the 677 million children aged younger than 5 years worldwide representing 58 countries. We reported the number of annual national RSV-associated ALRI hospitalisations for 29 countries using the rate-based method, and for 42 countries using the proportion-based method. The median number of RSV-associated ALRI hospitalisations in children younger than 5 years was 8·25 thousand (IQR 1·97-48·01), and the median rate of RSV-associated ALRI hospitalisations was 514 (339-866) hospitalisations per thousand children younger than 5 years. Despite large variation among countries, a high proportion of the RSV-associated ALRI hospitalisations were in infants aged younger than 1 year in all countries (median proportion 45%, IQR 32-56). In 272 (76%) of the 358 years included in the analysis, the RSV-associated ALRI hospitalisation rate fluctuated between 0·8 and 1·2 times the country's median yearly rate. General agreement was observed between estimates by the rate-based method and proportion-based method, with the exceptions of India, Kenya, Norway, and Philippines. By incorporating data from various sources, our study provides robust estimates on national level burden of RSV-associated ALRI hospitalisation in children aged younger than 5 years. These estimates are important for informing policy for the introduction of RSV immunisations and also serve as baseline data for the RSV disease burden in young children. The Foundation for Influenza Epidemiology.


Thymic output changes in children with clinical findings signaling a probable primary immunodeficiency.
Karaca N, Azarsız E, Akarcan SE, Aksu G, Kütükçüler N. Thymic output changes in children with clinical findings signaling a probable primary immunodeficiency. Turk J Pediatr 2019; 61: 885-894. Thymic maturation evaluation is inevitable for patients with clinical and laboratory findings for a primary immunodeficiency, as the T cellimmunodeficiencies are the most severe type. In this study, we aimed to show the usage of T cell surface molecule `CD31` for the evaluation of thymic output in patients (n: 66) with a large spectrum of findings signing a probable primary immunodeficiency. Besides the classical clinical and laboratory approach for these patients, T cell subpopulations as naive, memory, recent thymic emigrant cells were also investigated. The humoral immunodeficiency (34.8%), combined immunodeficiency (34.8%) and cardiopathy (7.6%) were the most frequent diagnosis groups. CD4+CD45RA+ naive T-cells percentages (p: 0.011) and absolute counts (p: 0.004) and absolute CD4+CD45RA+CD31+ RTE (recent thymic emigrant) cell counts (p: 0.007) were significantly lower in combined immunodeficiency group. Naive T-cells (p: 0.037) and RTE cells (p: 0.032) were also lower in patients who had cardiac surgery in the past. In conclusion, flow cytometric CD31+thymic naive RTE cell evaluation may provide rapid clinical information especially on T-cell immune dysfunction and CD4+CD45RA+CD31+ RTE cells may be used as an alternative to TRECs in the diagnosis of combined immunodeficiencies.


Dual Photoisomerization on Distinct Potential Energy Surfaces in a UV-Absorbing Rhodopsin.
UV-absorbing rhodopsins are essential for UV vision and sensing in all kingdoms of life. Unlike the well-known visible-absorbing rhodopsins, which bind a protonated retinal Schiff base for light absorption, UV-absorbing rhodopsins bind an unprotonated retinal Schiff base. Thus far, the photoreaction dynamics and mechanisms of UV-absorbing rhodopsins have remained essentially unknown. Here, we report the complete excited- and ground-state dynamics of the UV form of histidine kinase rhodopsin 1 (HKR1) from eukaryotic algae, using femtosecond stimulated Raman spectroscopy (FSRS) and transient absorption spectroscopy, covering time scales from femtoseconds to milliseconds. We found that energy-level ordering is inverted with respect to visible-absorbing rhodopsins, with an optically forbidden low-lying S1 excited state that has Ag- symmetry and a higher-lying UV-absorbing S2 state of Bu+ symmetry. UV-photoexcitation to the S2 state elicits a unique dual-isomerization reaction: first, C13═C14 cis-trans isomerization occurs during S2-S1 evolution in <100 fs. This very fast reaction features the remarkable property that the newly formed isomer appears in the excited state rather than in the ground state. Second, C15═N16 anti-syn isomerization occurs on the S1-S0 evolution to the ground state in 4.8 ps. We detected two ground-state unprotonated retinal photoproducts, 13-trans/15-anti (all-trans) and 13-cis/15-syn, after relaxation to the ground state. These isomers become protonated in 58 μs and 3.2 ms, respectively, resulting in formation of the blue-absorbing form of HKR1. Our results constitute a benchmark of UV-induced photochemistry of animal and microbial rhodopsins.


Challenges in meta-analyses with observational studies.
Meta-analyses of observational studies are frequently published in the literature, but they are generally considered suboptimal to those involving randomised controlled trials (RCTs) only. This is due to the increased risk of biases that observational studies may entail as well as because of the high heterogeneity that might be present. In this article, we highlight aspects of meta-analyses with observational studies that need more careful consideration in comparison to meta-analyses of RCTs. We present an overview of recommendations from the literature with respect to how the different steps of a meta-analysis involving observational studies should be comprehensively conducted. We focus more on issues arising at the step of the quantitative synthesis, in terms of handling heterogeneity and biases. We briefly describe some sophisticated synthesis methods, which may allow for more flexible modelling approaches than common meta-analysis models. We illustrate the issues encountered in the presence of observational studies using an example from mental health, which assesses the risk of myocardial infarction in antipsychotic drug users. The increased heterogeneity observed among studies challenges the interpretation of the diamond, while the inclusion of short exposure studies may lead to an exaggerated risk for myocardial infarction in this population. In the presence of observational study designs, prior to synthesis, investigators should carefully consider whether all studies at hand are able to answer the same clinical question. The potential for a quantitative synthesis should be guided through examination of the amount of clinical and methodological heterogeneity and assessment of possible biases.


Interactions of copper and pyrene on phytoremediation potential of Brassica juncea in copper-pyrene co-contaminated soil.
Phytoremediation which is a plant based remediation process is an emerging technology for treating inorganic (heavy metals) as well as organic pollutants. It may also be suitable for remediation of sites co-contaminated with heavy metals and organics which have become more prevalent. A glasshouse experiment was carried out to investigate the effect of 50 and 100 mg kg(-1) of copper or 250 and 500 mg kg(-1) of pyrene and the combined effect of copper and pyrene on the growth of Brassica juncea together with the uptake and accumulation of copper as well as dissipation of pyrene. Results showed a negative effect of copper-pyrene co-contamination on shoot and root dry matter and an inhibition of copper phytoextraction. Pyrene was significantly decreased in planted and non-planted soils accounting for 90-94% of initial extractable concentration in soil planted with B. juncea and 79-84% in non-planted soil which shows that the dissipation of pyrene was enhanced with planting. The occurrence of copper tended to increase the residual pyrene in planted soil, however in the presence of high concentration of Cu (100 mg kg(-1)), the residual pyrene concentration in soil were similar to those in unplanted soil. This may suggest that changes in the root physiology or rhizospheric microbial activity resulting from Cu stress could be an impediment to pyrene dissipation. The inhibition of Cu phytoextraction and degradation of pyrene by B. juncea under co-contamination may reduce the viability of phytoremediation in sites containing multiple pollutants.


Role of elevated pressure in TRAIL-induced apoptosis in human lung carcinoma cells.
TNF-related apoptosis-inducing ligand (TRAIL, Apo2L) is a promising anticancer agent with high specificity for cancer cells. Many strategies have been proposed to enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis, including the use of combination treatment with conventional cancer therapies. However, few reports have evaluated the effects of TRAIL in combination with mechanical stress, which can also cause apoptosis of cancer cells. In the present study, we describe a custom-designed culture system that delivers two atmospheres of elevated pressure (EP) by using compressed air, and which enhances the sensitivity of cancer cells to TRAIL-mediated apoptosis. The combination of TRAIL and EP significantly increased apoptosis of human H460 lung cancer cells more than hyperbaric normoxia or normobaric mild hyperoxia. EP-potentiating TRAIL-mediated apoptosis of H460 cells was accompanied by up-regulated death receptor 5 (DR5), activation of caspases, decreased mitochondrial membrane potential, and reactive oxygen species production. We also observed EP-induced sensitization of TRAIL-mediated apoptosis in other cancer cell types. In contrast, human normal cells showed no DNA damage or cell death when exposed to the combined treatment. In a chicken chorioallantoic membrane model, EP enhanced TRAIL-mediated apoptosis of tumors that developed from transplanted H460 cells. Collectively, EP enhanced TRAIL-induced apoptosis of human lung carcinoma cells in vitro and in vivo. These findings suggest that EP is a mechanical and physiological stimulus that might have utility as a sensitizing tool for cancer therapy.


An efficient and rapid method for recovery of norovirus from food associated with outbreaks of gastroenteritis.
Noroviruses have emerged as the most common cause of foodborne outbreaks of acute nonbacterial gastroenteritis. In this study, two methods for the extraction of viruses from deli ham were compared. Using both methods, as little as 1 to 10 reverse transcription (RT)-PCR units of inoculated norovirus and enterovirus could be detected by nested RT-PCR assays. The fastest and most efficient extraction method based on TRIzol LS Reagent was chosen to identify viruses in food items associated with three different outbreaks. Norovirus was detected using nested (real time) RT-PCR assays that target the genome region routinely used for diagnosis of human cases, thereby facilitating the comparison of sequences detected in food and clinical specimens. For one outbreak, a norovirus sequence (163/163 nucleotides) identical to those detected in clinical samples was found on salami sliced by a food handler with a recent history of gastroenteritis. For the other two outbreaks, norovirus was detected on leftovers of spareribs and ham, but fecal samples from affected persons were not available. The methods used in this study may be useful in future outbreak investigations because the extraction method is easy to perform and suitable for this particular type of food and the detection method facilitates direct comparison of patient and food data.


Effect of nitrosylmyoglobin and saturated fatty acid anions on metmyoglobin-catalyzed oxidation of aqueous methyl linoleate emulsions.
In aqueous methyl linoleate emulsions (pH 7.4, 25 degrees C, air-saturated), nitrosylmyoglobin and saturated fatty acid anions (palmitate and stearate investigated) each showed antioxidant effect on metmyoglobin-induced peroxidation as measured by oxygen depletion rate. For equimolar concentration of nitrosylmyoglobin and metmyoglobin and for metmyoglobin in moderate excess, a reduction in oxygen consumption rate of approximately 70% was observed. Fatty acid anions reduced oxygen consumption rate most significantly for palmitate (up to 60% for a fatty acid:heme protein ratio of 90:1). No further antioxidative effect was seen for fatty acid anions in the presence of nitrosylmyoglobin, whereas nitrosylmyoglobin showed a further antioxidant effect in presence of fatty acid anions in the metmyoglobin-catalyzed process. The antioxidative mechanism of nitrosylmyoglobin and fatty acid anions is different, and while the fatty acid anions seem active in inhibiting initiation of oxidation through protection against metmyoglobin activation into perferrylmyoglobin, as shown by freeze-quench Electron Spin Resonance (ESR) spectroscopy, nitrosylmyoglobin is rather active in the oxygen consuming (propagation) phase.


Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the rapid identification of yeasts causing bloodstream infections.
Few studies have systematically standardised and evaluated matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of yeasts from bloodstream infections. This is rapidly becoming pertinent for early identification of yeasts and appropriate antifungal therapy. We used 354 yeast strains identified by polymerase chain reaction (PCR) sequencing for standardisation and 367 blind clinical strains for validation of our MALDI-TOF MS protocols. We also evaluated different sample preparation methods and found the on-plate formic acid extraction method as most cost- and time-efficient. The MALDI-TOF assay correctly identified 98.9% of PCR-sequenced yeasts. Novel main spectrum projections (MSP) were developed for Candida auris, C. viswanathii and Kodamaea ohmeri, which were missing from the Bruker MALDI-TOF MS database. Spectral cut-offs computed by receiver operating characteristics (ROC) analysis showed 99.4% to 100% accuracy at a log score of ≥ 1.70 for C. tropicalis, C. parapsilosis, C. pelliculosa, C. orthopsilosis, C. albicans, C. rugosa, C. guilliermondii, C. lipolytica, C. metapsilosis, C. nivariensis. The differences in the species-specific scores of our standardisation and blind validation strains were not statistically significant, implying the optimal performance of our test protocol. The MSPs of the three new species also were validated. We conclude that MALDI-TOF MS is a rapid, accurate and reliable tool for identification of bloodstream yeasts. With proper standardisation, validation and regular database expansion, its efficiency can be further enhanced.


Precise subnanometer plasmonic junctions for SERS within gold nanoparticle assemblies using cucurbit[n]uril "glue".
Cucurbit[n]urils (CB[n]) are macrocyclic host molecules with subnanometer dimensions capable of binding to gold surfaces. Aggregation of gold nanoparticles with CB[n] produces a repeatable, fixed, and rigid interparticle separation of 0.9 nm, and thus such assemblies possess distinct and exquisitely sensitive plasmonics. Understanding the plasmonic evolution is key to their use as powerful SERS substrates. Furthermore, this unique spatial control permits fast nanoscale probing of the plasmonics of the aggregates "glued" together by CBs within different kinetic regimes using simultaneous extinction and SERS measurements. The kinetic rates determine the topology of the aggregates including the constituent structural motifs and allow the identification of discrete plasmon modes which are attributed to disordered chains of increasing lengths by theoretical simulations. The CBs directly report the near-field strength of the nanojunctions they create via their own SERS, allowing calibration of the enhancement. Owing to the unique barrel-shaped geometry of CB[n] and their ability to bind "guest" molecules, the aggregates afford a new type of in situ self-calibrated and reliable SERS substrate where molecules can be selectively trapped by the CB[n] and exposed to the nanojunction plasmonic field. Using this concept, a powerful molecular-recognition-based SERS assay is demonstrated by selective cucurbit[n]uril host-guest complexation.


Exercise-induced neurocardiogenic syncope: clinical data, pathophysiological aspects, and potential role of tilt table testing.
The evaluation of syncope occurring during exercise or occurring spontaneously in highly trained individuals presents a unique diagnostic challenge. It is of critical importance to exclude potential life-threatening disorders such as hypertrophic cardiomyopathy, long QT syndrome, right ventricular dysplasia, anomalous coronary artery distribution, valvular heart disease, myocarditis, or exercise-induced arrhythmia. This review is not directed towards identifying, treating, or determining athletic eligibility of individuals with such disorders. Rather, we endeavour to discuss the pathophysiology of exercise-induced neurocardiogenic syncope and to address the role of head upright tilt testing in evaluating syncope in athletic individuals in whom proper evaluation has excluded the presence of ischaemic heart disease or primary structural or electrical heart disease.


Synergistic and suppressive interactions among mouse T lymphocytes in the response to phytohemagglutinin.
A synergistic effect in the proliferative response to phytohemagglutinin (PHA) can be observed in cultures containing a mixture of mouse CBA/Ca lymph node cells (LNC) and syngeneic CBA/T6T6 thymocytes (ThC) when compared to cultures containing only one cell type. This effect was analyzed, at various days of culture and in LNC-ThC mixtures of different ratios, by comparing the origin of the cells in mitosis (detected by caryotypic analysis), the stimulation of DNA synthesis, the number of blasts, and the percentage of blasts labeled after pulses of [3H]thymidine (detected by autoradiography). The following conclusions were reached: (a) ThC are induced to proliferate by the presence of LNC, while they are almost unresponsive to PHA when cultured alone; and (b) the strongest "synergistic" effect is exerted on LNC, whose proliferation is markedly enhanced. Evidence is presented that this last effect is not specific to the presence of ThC, but results from a dilution of LNC which retards the time when the culture reaches a critical concentration of blasts, above which proliferation progressively stops. Thus, conditions of culture allowing the response to PHA of a low concentration of LNC leads to the most prolonged T-cell proliferation. These observations may be relevant to the types of T-cell interactions, "synergistic" or "suppressive," occurring during in vitro or in vivo immune responses.


Rofenaid in the control of Pasteurella anatipestifer and Escherichia coli infections in ducklings.
In a series of controlled battery trials, Rofenaid (at doses ranging from 0.02 to 0.12% active drug in feed) was administered to ducklings infected experimentally with Pasteurella anatipestifer and Escherichia coli strains. Against P. anatipestifer, Rofenaid at 0.02 to 0.12% levels in feed either prevented or reduced mortality, gross lesions, and bacterial isolations. Furthermore, the weight gain and feed conversion of infected Rofenaid-medicated ducklings were superior to those of uninfected unmedicated controls in two out of three trials. Against E. coli, Rofenaid at 0.02 to 0.08% levels in feed either prevented or reduced mortality, gross lesions, and bacterial isolations. Weight gain and feed conversion of infected Rofenaid-medicated ducklings were also superior to those of uninfected unmedicated controls in two out of three trials. It appears that Rofenaid, at a 0.02-0.08% level, controls infections in ducklings caused by P. anatipestifer and E. coli strains sensitive to this compound.


Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis.
The approval of bedaquiline (BDQ) for the treatment of tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death in Mycobacterium tuberculosis (Mtb). Using 13C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon metabolism to induce a metabolically vulnerable state susceptible to genetic disruption of glycolysis and gluconeogenesis. Metabolic flux profiles indicate that BDQ-treated Mtb is dependent on glycolysis for ATP production, operates a bifurcated TCA cycle by increasing flux through the glyoxylate shunt, and requires enzymes of the anaplerotic node and methylcitrate cycle. Targeting oxidative phosphorylation (OXPHOS) with BDQ and simultaneously inhibiting substrate level phosphorylation via genetic disruption of glycolysis leads to rapid sterilization. Our findings provide insight into the metabolic mechanism of BDQ-induced cell death and establish a paradigm for the development of combination therapies that target OXPHOS and glycolysis.


Allocating health care: cost-utility analysis, informed democratic decision making, or the veil of ignorance?
Assuming that rationing health care is unavoidable, and that it requires moral reasoning, how should we allocate limited health care resources? This question is difficult because our pluralistic, liberal society has no consensus on a conception of distributive justice. In this article I focus on an alternative: Who shall decide how to ration health care, and how shall this be done to respect autonomy, pluralism, liberalism, and fairness? I explore three processes for making rationing decisions: cost-utility analysis, informed democratic decision making, and applications of the veil of ignorance. I evaluate these processes as examples of procedural justice, assuming that there is no outcome considered the most just. I use consent as a criterion to judge competing processes so that rationing decisions are, to some extent, self-imposed. I also examine the processes' feasibility in our current health care system. Cost-utility analysis does not meet criteria for actual or presumed consent, even if costs and health-related utility could be measured perfectly. Existing structures of government cannot creditably assimilate the information required for sound rationing decisions, and grassroots efforts are not representative. Applications of the veil of ignorance are more useful for identifying principles relevant to health care rationing than for making concrete rationing decisions. I outline a process of decision making, specifically for health care, that relies on substantive, selected representation, respects pluralism, liberalism, and deliberative democracy, and could be implemented at the community or organizational level.


The toxicity of Burttia prunoides in rats and goats.
Studies of the toxicity of the leaves and seeds of the plant Burttia prunoides from Singida district of Tanzania were conducted in rats and goats. One group of rats was drenched with a decoction of powdered seeds or leaves while the other group was fed rations containing different proportions of powdered seeds or leaves. The goats were drenched with aqueous suspensions of powdered seeds or leaves. All animals were observed for behavioral changes and clinical signs. Leaves were not toxic to the rats or the goats. In rats the seeds induced a severe acute central nervous system (CNS) disorder and death and also a subacute syndrome characterized by emaciation and milder CNS signs. In goats the seeds induced a severe CNS disorder where unlike the rats the animals did recover. Postmortem findings in the rats included hemorrhage and inflammation of the glandular stomach and edema and congestion of the lungs, brain and mucosa of the gastrointestinal tract. The kidneys were congested and showed complete nephrosis of the proximal tubular epithelium. Livers were congested and had focal areas of necrosis. The findings in this study resemble those obtained in calves and sheep using the same plant.


Influence of oxygenation on chromium redox reactions with manganese sulfide (MnS(s)).
Manganese sulfide (MnS(s)) minerals exist in sulfidic environments and can have unique reactive abilities because of sulfide, which is a known reductant, and Mn, the oxyhydroxides of which are known oxidants. This study elucidated the role of MnS(s) in controlling Cr speciation with implications on its fate and toxicity in the natural environment, specifically sulfidic sediments that undergo biogeochemical changes due to sediment resuspension during dredging, bioturbation, and flood events. In continuously mixed batch reaction experiments, aqueous CrVI reduction under anaerobic conditions occurred primarily on the surface of MnS(s) displaying a biphasic behavior- the initial rapid removal of CrVI from solution was followed by a slow decline due to surface passivation by reaction products, mainly sorbed or precipitated CrIII. The reaction progress increased with MnS(s) surface area loading but decreased on increasing CrVI concentration and pH, suggesting that surface site regeneration through product desorption was the rate-controlling mechanism. Below circum-neutral pH, higher solubility of MnS(s) resulted in additional CrVI reduction by reduced sulfur species in solution, whereas increased CrIII solubility lowered surface passivation allowing for more reactive sites to participate in the reaction. Aeration of MnS(s) at pH≥7 caused the formation of a heterogeneous MnIII(hydr)oxide that was composed of hausmanite and manganite. CrVI reoccurrence was observed on aeration of CrVI-spiked MnS(s) from the oxidation of product CrIII. The reoccurrence at pH≥7 was attributed to the oxidation of product CrIII by MnIII(hydr)oxide, whereas the reoccurrence at pH<7 was hypothesized from the oxidation of product CrIII by intermediate aqueous MnIII and/or sulfur species. Just as with Cr, MnS(s) may play an important role in speciation, fate, and transport of other environmental contaminants.


Electrical Microstimulation of the Pulvinar Biases Saccade Choices and Reaction Times in a Time-Dependent Manner.
The pulvinar complex is interconnected extensively with brain regions involved in spatial processing and eye movement control. Recent inactivation studies have shown that the dorsal pulvinar (dPul) plays a role in saccade target selection; however, it remains unknown whether it exerts effects on visual processing or at planning/execution stages. We used electrical microstimulation of the dPul while monkeys performed saccade tasks toward instructed and freely chosen targets. Timing of stimulation was varied, starting before, at, or after onset of target(s). Stimulation affected saccade properties and target selection in a time-dependent manner. Stimulation starting before but overlapping with target onset shortened saccadic reaction times (RTs) for ipsiversive (to the stimulation site) target locations, whereas stimulation starting at and after target onset caused systematic delays for both ipsiversive and contraversive locations. Similarly, stimulation starting before the onset of bilateral targets increased ipsiversive target choices, whereas stimulation after target onset increased contraversive choices. Properties of dPul neurons and stimulation effects were consistent with an overall contraversive drive, with varying outcomes contingent upon behavioral demands. RT and choice effects were largely congruent in the visually-guided task, but stimulation during memory-guided saccades, while influencing RTs and errors, did not affect choice behavior. Together, these results show that the dPul plays a primary role in action planning as opposed to visual processing, that it exerts its strongest influence on spatial choices when decision and action are temporally close, and that this choice effect can be dissociated from motor effects on saccade initiation and execution.SIGNIFICANCE STATEMENT Despite a recent surge of interest, the core function of the pulvinar, the largest thalamic complex in primates, remains elusive. This understanding is crucial given the central role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar (dPul) are rare. Building on our previous studies that pharmacologically suppressed dPul activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision making. We show that stimulation effects depend on timing and behavioral state and that effects on choices can be dissociated from motor effects.


The impact of gambling advertising: Problem gamblers report stronger impacts on involvement, knowledge, and awareness than recreational gamblers.
Although there is a general lack of empirical evidence that advertising influences gambling participation, the regulation of gambling advertising is hotly debated among academic researchers, treatment specialists, lobby groups, regulators, and policymakers. This study contributes to the ongoing debate by investigating perceived impacts of gambling advertising in a sample of gamblers drawn from the general population in Norway (n = 6,034). Three dimensions of advertising impacts were identified, representing perceived impacts on (a) gambling-related attitudes, interest, and behavior ("involvement"); (b) knowledge about gambling options and providers ("knowledge"); and (c) the degree to which people are aware of gambling advertising ("awareness"). Overall, impacts were strongest for the knowledge dimension, and, for all 3 dimensions, the impact increased with level of advertising exposure. Those identified as problem gamblers in the sample (n = 57) reported advertising impacts concerning involvement more than recreational gamblers, and this finding was not attributable to differences in advertising exposure. Additionally, younger gamblers reported stronger impacts on involvement and knowledge but were less likely to agree that they were aware of gambling advertising than older gamblers. Male gamblers were more likely than female gamblers to report stronger impacts on both involvement and knowledge. These findings are discussed with regard to existing research on gambling advertising as well as their implications for future research and policy-making. (PsycINFO Database Record


Almost periodic quasi-projective synchronization of delayed fractional-order quaternion-valued neural networks.
This paper examines the issue of almost periodic quasi-projective synchronization of delayed fractional-order quaternion-valued neural networks. First, using a direct method rather than decomposing the fractional quaternion-valued system into four equivalent fractional real-valued systems, using Banach's fixed point theorem, according to the basic properties of fractional calculus and some inequality methods, we obtain that there is a unique almost periodic solution for this class of neural network with some sufficient conditions. Next, by constructing a suitable Lyapunov functional, using the characteristic of the Mittag-Leffler function and the scaling idea of the inequality, the adequate conditions for the quasi-projective synchronization of the established model are derived, and the upper bound of the systematic error is estimated. Finally, further use Matlab is used to carry out two numerical simulations to prove the results of theoretical analysis.


Effect of protein content and denaturation on the extractability and stability of isoflavones in different soy systems.
The effect of protein on the thermal stability of isoflavones and the efficiency of their extraction from various soy matrixes was investigated. Isoflavones were extracted from soymilk, soybean. and soy protein isolate, varying in protein content and/or denaturation state, following nonenzyme-assisted solvent extraction or enzyme-assisted extraction. Selected samples were subjected to thermal treatment prior to and posthydrolysis of the protein. The extraction efficiency was a function of the enzyme used, sample to solvent ratio, protein content, and protein denaturation state. Proteolysis and reducing the sample to solvent ratio enhanced the isoflavone extractability, especially in samples with denatured protein. Results demonstrated clearly that the solvent extraction techniques currently used considerably underestimate isoflavone content in complex soy systems with high protein content. The stability of isoflavones was reduced upon protein hydrolysis, indicating that the protein moiety may have a protective effect against the thermal degradation of isoflavones.


Black spots in the returning traveler.
African tick bite fever (ATBF) is a rickettsial infection that should be considered as the cause of fever in travelers returning from endemic regions of sub-Saharan Africa or the Caribbean. Patients typically present with a flu-like syndrome and may demonstrate one or more cutaneous inoculation eschars as a diagnostic key. We present a case of ATBF in a pregnant woman following her trip to Swaziland. Her symptoms rapidly improved with institution of effective antimicrobial treatment with azithromycin and rifampin; she made a full recovery.