The aryl hydrocarbon receptor: A predominant mediator for the toxicity of emerging dioxin-like compounds.
The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family of transcription factors and has broad biological functions. Early after the identification of the AHR, most studies focused on its roles in regulating the expression of drug-metabolizing enzymes and mediating the toxicity of dioxins and dioxin-like compounds (DLCs). Currently, more diverse functions of AHR have been identified, indicating that AHR is not just a dioxin receptor. Dioxins and DLCs occur ubiquitously and have diverse health/ecological risks. Additional research is required to identify both shared and compound-specific mechanisms, especially for emerging DLCs such as polyhalogenated carbazoles (PHCZs), polychlorinated diphenyl sulfides (PCDPSs), and others, of which only a few investigations have been performed at present. Many of the toxic effects of emerging DLCs were observed to be predominantly mediated by the AHR because of their structural similarity as dioxins, and the in vitro TCDD-relative potencies of certain emerging DLC congeners are comparable to or even greater than the WHO-TEFs of OctaCDD, OctaCDF, and most coplanar PCBs. Due to the close relationship between AHR biology and environmental science, this review begins by providing novel insights into AHR signaling (canonical and non-canonical), AHR's biochemical properties (AHR structure, AHR-ligand interaction, AHR-DNA binding), and the variations during AHR transactivation. Then, AHR ligand classification and the corresponding mechanisms are discussed, especially the shared and compound-specific, AHR-mediated effects and mechanisms of emerging DLCs. Accordingly, a series of in vivo and in vitro toxicity evaluation methods based on the AHR signaling pathway are reviewed. In light of current advances, future research on traditional and emerging DLCs will enhance our understanding of their mechanisms, toxicity, potency, and ecological impacts.


Mechanism of action of ribulose bisphosphate carboxylase/oxygenase.
RuBP carboxylase-oxygenase appears to catalyze carboxylation and oxygenation by homologous mechanisms. A common binding site exists on the enzyme for the acceptor substrate, RuBP. A mechanism is proposed whereby RuBP is isomerized, and a carbanion is generated at C2. Then, either CO2 or O2 is added as an electrophile at C2 to form the corresponding 3-keto-2-carboxy-RBP or 3-keto-2-hydroperoxy-RBP adduct. Hydrolytic cleavage at the C2-C3 bonds of these intermediates by the enzyme is envisioned to produce 2 molecules of 3-phosphoglycerate in the carboxylation sequence and 1 molecule of phosphoglycolate and 1 molecule of 3-phosphoglycerate in the oxygenation sequence. Further work will be necessary to establish the validity of the proposed mechanism.


Short-term incidental memory for irrelevant cues.
A new analysis of previously published studies of delayed matching-to-sample (DMTS) water-escape and the results of a new food-reinforced discrimination study are presented. In both cases, male Sprague-Dawley rats demonstrated short-term incidental memory for irrelevant cues in the context of two-alternative forced-choice problems that required learning about relevant cues. In the DMTS experiments, relevant and irrelevant cues were place or brightness. In the discrimination experiment, the relevant cues were place, brightness or a visual-tactile maze insert. In all experiments, after the rats attained high-level performance, consistently making choices with respect to the relevant stimuli, response latencies to the correct relevant cue were shorter when the irrelevant cue value(s) was the same as on the immediately preceding trial. These latency differences are interpreted as indicating that the rats demonstrated short-term incidental memory for the irrelevant cues. This mnemonic phenomenon resembles priming, an implicit form of memory.


Tumefactive appearance of peripheral nerve involvement in hematologic malignancies: a new imaging association.
In neurolymphomatosis (NL), the affected nerves are typically described to be enlarged and hyperintense on T2W MR sequences and to avidly enhance on gadolinium-enhanced T1WI. This pattern is highly non-specific. We recently became aware of a "tumefactive pattern" of NL, neuroleukemiosis (NLK) and neuroplasmacytoma (NPLC), which we believe is exclusive to hematologic diseases affecting peripheral nerves. We defined a "tumefactive" appearance as complex, fusiform, hyperintense on T2WI, circumferential tumor masses encasing the involved peripheral nerves. The nerves appear to be infiltrated by the tumor. Both structures show varying levels of homogenous enhancement. We reviewed our series of 52 cases of NL in search of this pattern; two extra outside cases of NL, three cases of NLK, and one case of NPLC were added to the series. We identified 20 tumefactive lesions in 18 patients (14 NL, three NLK, one NPLC). The brachial plexus (n = 7) was most commonly affected, followed by the sciatic nerve (n = 6) and lumbosacral plexus (n = 3). Four patients had involvement of other nerves. All were proven by biopsy: the diagnosis was high-grade lymphoma (n = 12), low-grade lymphoma (n = 3), acute leukemia (n = 2), and plasmacytoma (n = 1). We present a new imaging pattern of "tumefactive" neurolymphomatosis, neuroleukemiosis, or neuroplasmacytoma in a series of 18 cases. We believe this pattern is associated with hematologic diseases directly involving the peripheral nerves. Knowledge of this association can provide a clue to clinicians in establishing the correct diagnosis. Bearing in mind that tumefactive NL, NLK, and NPLC is a newly introduced imaging pattern, we still recommend to biopsy patients with suspicion of a malignancy.


Effect of isoorientin on intracellular antioxidant defence mechanisms in hepatoma and liver cell lines.
Isoorientin (ISO) is considered one of the most important flavonoid-like compounds responsible for health benefits, including the prevention of liver damage as well as antioxidant, anti-inflammatory, and anti-nociceptive activities. Our previous study showed that ISO inhibited the proliferation of hepatoma cells through increasing intracellular ROS levels. Interestingly, ISO protects rat liver cells against hydrogen peroxide-induced oxidation stress by decreasing intracellular ROS levels. Why are there different effects of ISO on ROS in different physiological and pathophysiological circumstances? The present study investigated the effect of ISO on mitochondrial respiratory chain complexes and phase II detoxifying enzyme activities in human hepatoblastoma cancer cells (HepG2), buffalo rat liver cells (BRL-3A) and human liver cancer cells (HL-7702). The results showed that intracellular ROS levels and the protein expression of the respiratory chain complexes was significantly (p<0.01) higher in the HepG2 cells than in the BRL-3A and HL-7702 cells. Additionally, ISO notably (p<0.01) increased ROS levels in the HepG2 cells, while no significance was found in the BRL-3A and HL-7702 cells. Furthermore, in the HepG2 cells, the protein expression of the respiratory chain complexes and the phase II detoxifying enzyme activities and GSH content were decreased by ISO (p<0.01), while ISO, in a certain range, enhanced the expression of the protein complexes and the phase II detoxifying enzyme activities and GSH content in BRL-3A and HL-7702 cells. All of these results demonstrated, for the first time, that ISO possesses a notable hepatoprotective effect, which might be mediated through the respiratory chain complexes and phase II detoxifying enzyme activities.


[Esthetic dermatology for the elderly].
Esthetic dermatology discovers older age. Methods and techniques which are useful in younger people need modifications to meet the special needs of the elderly. These aspects are discussed with a focus on the aging face. Esthetic dermatology is most successful when using principles of regenerative medicine.


Mechanisms underlying saturable intestinal absorption of metformin.
The purpose of the study was to elucidate mechanisms of metformin absorptive transport to explain the dose-dependent absorption observed in humans. Apical (AP) and basolateral (BL) uptake and efflux as well as AP to BL (absorptive) transport across Caco-2 cell monolayers were evaluated over a range of concentrations. Transport was concentration-dependent and consisted of saturable and nonsaturable components (K(m) approximately 0.05 mM, J(max) approximately 1.0 pmol min(-1) cm(-2), and K(d, transport) approximately 10 nl min(-1) cm(-2)). AP uptake data also revealed the presence of saturable and nonsaturable components (K(m) approximately 0.9 mM, V(max) approximately 330 pmol min(-1) mg of protein(-1), and K(d, uptake) approximately 0.04 microl min(-1) mg of protein(-1)). BL efflux was rate-limiting to transcellular transport of metformin; AP efflux was 7-fold greater than BL efflux and was not inhibited by N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GW918), a P-glycoprotein inhibitor. AP efflux was trans-stimulated by metformin and prototypical substrates of organic cation transporters, suggesting that a cation-specific bidirectional transport mechanism mediated the AP efflux of metformin. BL efflux of intracellular metformin was much less efficient in comparison with the overall transport, with BL efflux clearance accounting for approximately 7 and approximately 13% of the overall transport clearance at 0.05 and 10 mM metformin concentrations, respectively. Kinetic modeling of cellular accumulation and transport processes supports the finding that transport occurs almost exclusively via the paracellular route (approximately 90%) and that the paracellular transport is saturable. This report provides strong evidence for a saturable mechanism in the paracellular space and provides insight into possible mechanisms for the dose dependence of metformin absorption in vivo.


Adsorption and photocatalytic degradation of anionic dyes on Chitosan/PVA/Na-Titanate/TiO2 composites synthesized by solution casting method.
Chitosan/PVA/Na-titanate/TiO2 composite was synthesized by solution casting method. The composite was analyzed via Fourier Transform Infrared Spectroscopy, X-ray diffraction, Field Emission Scanning Electron Microscopy, Thermal gravimetric analysis and water stability test. Incorporation of Na-titanate shown decrease of crystallinity for chitosan but increase water stability. However, the composite structure was deteriorated with considerable weight loss in acidic medium. Two anionic dyes, methyl orange and congo red were used for the adsorption test. The adsorption behavior of the composites were described by pseudo-second-order kinetic model and Lagergren-first-order model for methyl orange and congo red, respectively. For methyl orange, adsorption was started with a promising decolorization rate. 99.9% of methyl orange dye was removed by the composite having higher weightage of chitosan and crystalline TiO2 phase. On the other hand, for the congo red the composite having higher chitosan and Na-titanate showed an efficient removal capacity of 95.76%. UV-vis results showed that the molecular backbone of methyl orange and congo red was almost destroyed when equilibrium was obtained, and the decolorization rate was reaching 100%. Kinetic study results showed that the photocatalytic degradation of methyl orange and congo red could be explained by Langmuir-Hinshelwood model. Thus, chitosan/PVA/Na-titanate/TiO2 possesses efficient adsorptivity and photocatalytic property for dye degradation.


Liver X receptors: From pharmacology to nanoparticle-based drug delivery.
Liver X receptors (LXRs) are master regulators of various biological processes, including metabolism, inflammation, development, and reproduction. As well-known nuclear oxysterol receptors of the nuclear receptor (NR) family, LXRs have two homologous subtypes, LXRα (NR1H3) and LXRβ (NR1H2). Since the mid-1990s, numerous LXR-targeted drugs have been designed to treat diseases such as atherosclerosis, systemic lupus erythematosus, and cancer. These modulators include agonists and antagonists, and the selectivity of them have been development from diverse aspects, including subtype-specific, cell-specific, tissue-specific types. Meanwhile, advanced delivery systems are also exploreed to facilitate the application of LXR drugs in clinical setting. One of the most promising delivery systems involves the use of nanoparticles and is expected to increase the clinical potential of LXR modulators. This review discusses our current understanding of LXR biology and pharmacology, focusing on the development of modulators for LXRα and/or LXRβ, and the nanoparticle-based delivery systems for promising LXR modulators with potential for use as drugs.


Single metastases in the brain: late results in 325 cases.
The authors report on the results obtained on a series of 325 patients operated on for single brain metastasis at the Institute of Neurosurgery of the University of Rome during the period 1951-1979. After analyzing the results vis-à-vis the site of the brain metastasis, the site of the primitive tumour and the surgical treatment administered; emphasis is given to the importance of the advent of the CT scan which has permitted a more accurate selection of the patients resulting in improvement in operative mortality and average survival time which at present is one year.


Autoradiographic study of glycoprotein synthesis during embryonic epidermogenesis of the mouse in vitro.
Forelimb buds of mouse embryos (day 11 + 3 h of development) were cultured for 6 days. During this period, the epidermis developed from a two-layered stage (basal and periderm cell layer) to a multilayered squamous epithelium wih stratum granulosum and stratum corneum. To investigate the glycoprotein synthesis during epidermogenesis in vitro, the limb buds were labeled for 30 min or 4 h with 3H-fucose at successive stages of development. Until the development of the stratum intermedium, no different labeling of the individual layers of the epidermis and the periderm was observed. Shortly before the beginning of the stratum granulosum, a strong labeling of the outer region of the intermediate layer, where the shape of the cells had changed from cuboid to flat, was visible. When the stratum granulosum developed, even in this layer and in the upper stratum spinosum, strong glycoprotein synthesis was observed, indicated by strong labeling with 3H-fucose. In the developing stratum corneum, no labeling of this layer was detectable 30 min or 4 h after 3H-fucose application. Labeling of peridermal cells was weak in the early stages of development and ceased in the period of stratum granulosum formation, indicating a stop of glycoprotein synthesis in this embryonal cell layer before its disappearance.


Granular activated carbon adsorption of MIB in the presence of dissolved organic matter.
Based on the results of over twenty laboratory granular activated carbon (GAC) column runs, models were developed and utilized for the prediction of 2-methylisoborneol (MIB) breakthrough behavior at parts per trillion levels and verified with pilot-scale data. The influent MIB concentration was found not to impact the concentration normalized breakthrough. Increasing influent background dissolved organic matter (DOM) concentration was found to systematically decrease the GAC adsorption capacity for MIB. A series of empirical models were developed that related the throughput in bed volumes for a range of MIB breakthrough targets to the influent DOM concentration. The proportional diffusivity (PD) designed rapid small-scale column test (RSSCT) could be directly used to scale-up MIB breakthrough performance below 15% breakthrough. The empirical model to predict the throughput to 50% breakthrough based on the influent DOM concentration served as input to the pore diffusion model (PDM) and well-predicted the MIB breakthrough performance below a 50% breakthrough. The PDM predictions of throughput to 10% breakthrough well simulated the PD-RSSCT and pilot-scale 10% MIB breakthrough.


Relation of acute antiarrhythmic drug efficacy to left ventricular function in coronary artery disease.
This study assessed the relation between acute antiarrhythmic drug efficacy and left ventricular (LV) function in patients with sustained ventricular tachyarrhythmias, that is, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Electrophysiologic studies (n = 560) were performed in 201 patients, separated for analysis into less than 30 and greater than or equal to 30% ejection fraction groups. Coronary artery disease was present in all patients. The 8 acute antiarrhythmic regimens were procainamide, quinidine, mexiletine, mexiletine + type 1A agent, flecainide or indecainide, amiodarone, amiodarone + type 1A and "miscellaneous" agents. At least 1 successful acute antiarrhythmic regimen was found in 47% of patients and in a significantly greater proportion of patients with ejection fraction greater than or equal to 30% (52 of 81 = 64%) than in those with ejection fraction less than 30% (43 of 120 = 36%, p less than 0.001). Drug trials were successful (initiation of less than 15 repetitive ventricular responses) in 32% of patients with ejection fraction greater than or equal to 30% versus 19% of those with ejection fraction less than 30% (p less than 0.001). There were no statistically significant differences between the 2 ejection fraction groups in type of heart disease, acute antiarrhythmic dosages or mean serum drug levels. A logistic regression analysis incorporating multiple clinically relevant factors found that ejection fraction was the only factor that correlated significantly with drug success or failure (p less than 0.002). Acute antiarrhythmic drug efficacy relates to LV function per se or to other pathophysiologic mechanisms of which ejection fraction may be a marker.


Cue-Evoked Dopamine Neuron Activity Helps Maintain but Does Not Encode Expected Value.
Cue-evoked midbrain dopamine (DA) neuron activity reflects expected value, but its influence on reward assessment is unclear. In mice performing a trial-based operant task, we test if bidirectional manipulations of cue or operant-associated DA neuron activity drive learning as a result of under- or overexpectation of reward value. We target optogenetic manipulations to different components of forced trials, when only one lever is presented, and assess lever biases on choice trials in the absence of photomanipulation. Although lever biases are demonstrated to be flexible and sensitive to changes in expected value, augmentation of cue or operant-associated DA signaling does not significantly alter choice behavior, and blunting DA signaling during any component of the forced trials reduces choice trial responses on the associated lever. These data suggest cue-evoked DA helps maintain cue-value associations but does not encode expected value as to set the benchmark against which received reward is judged.


A novel tetragonal T-C2N supported transition metal atoms as superior bifunctional catalysts for OER/ORR: From coordination environment to rational design.
Single-atom catalysts with particular electronic structures and precisely regulated coordination environments delivering excellent activity for oxygen-evolution reaction (OER) and oxygen-reduction reaction (ORR) are highly desirable for renewable energy applications. In this work, a novel tetragonal carbon nitride T-C2N monolayer with remarkable stability was predicted by using the RG2 method. Inspired by the well-defined atomic structures and just right N4 aperture of T-C2N substrate, the electrocatalytic performance of a series of transition metal single-atoms anchored on porous T-C2N matrix (TM@C2N) have been systematically investigated. In addition, machine learning (ML) method was employed with the gradient boosting regression GBR model to deeply explore the complex controlling factors and offer direct guidance for rational discovery of desirable catalysts. On this basis, the coordination environment of the central TM active sites has been tailored by incorporating heteroatoms. Impressively, the Co@C2N/B-C, Rh@C2N/SC and Rh@C2N/SN exhibit significantly enhanced OER/ORR activity with notably low ηOER/ηORR of 0.39/0.32, 0.26/0.35 and 0.37/0.27 V, respectively. Our work provides insights into the rational design, data-driven, performance regulation, mechanism analysis and practical application of TMNC catalysts. Such a systematic theoretical framework can also be expanded to many other kinds of catalysts for energy storage and conversion.


Imlifidase therapy: exploring its clinical uses.
Imlifidase, the IgG-degrading enzyme derived from Streptococcus pyogenes, can cleave all four human IgG subclasses with precise specificity. All IgG molecules can be inactivated for ~1-to-2 weeks, until new IgG synthesis is detected. Imlifidase was first studied for the desensitization of highly HLA-sensitized patients to enable kidney transplantation. It is currently being evaluated for kidney transplant recipients who have antibody-mediated rejection (AMR), those with acute kidney injury in the setting of anti-glomerular basement membrane disease, and those with Guillain-Barré syndrome. In 2020, imlifidase received conditional approval from the European Medicines Agency for use to desensitize deceased-donor kidney transplant recipients with a positive crossmatch. Literature search through PubMed revealed that so far, 39 crossmatched-positive patients, i.e. in the presence of donor-specific alloantibodies (DSA) on the transplantation day, have received imlifidase prior to kidney transplantation in four single-arm, open-label, phase II studies. Results at 3-year follow-up are good, i.e. allograft survival is 84%, despite 38% of patients presenting with acute AMR. Mean estimated glomerular filtration rate at 3 years was 55 mL/min/1.73 m2. The major hurdle now is how to prevent/avoid DSA rebound within days 5-15 post-transplantation. Thus, imlifidase represents a major breakthrough for highly HLA-sensitized kidney transplant candidates, particularly those that have calculated panel-reactive alloantibodies of ≥90%.


Sequential changes of dopaminergic receptors in the rat brain after 6-hydroxydopamine lesions of the medial forebrain bundle.
We investigated the sequential patterns of changes in dopamine uptake sites, D1 and D2 receptors in the brain of animals lesioned with 6-hydroxydopamine using quantitative receptor autoradiography. The rats were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks postlesion. Degeneration of the nigrostriatal pathway caused a significant loss of dopamine uptake sites in the ipsilateral striatum, substantia nigra (SN) and ventral tegmental area (VTA) in the lesioned animals. Dopamine D1 receptors were significantly increased in the ventromedial part of striatum of the ipsilateral side from 2 to 4 weeks postlesion. In the ipsilateral SN, a transient increase in dopamine D1 receptors was observed only 1 week after lesioning. However, the frontal cortex, parietal cortex and dorsolateral part of the striatum showed no significant change in dopamine D1 receptors throughout the experiments. On the other hand, dopamine D2 receptors were decreased increased in the ipsilateral SN and VTA from 1 week to 8 weeks postlesion. In the ipsilateral striatum, dopamine D2 receptors were increased in the dorsolateral part from 2 weeks to 8 weeks and in the ventromedial part from 2 weeks to 4 weeks. However, the frontal cortex and parietal cortex showed no significant change in dopamine D2 receptors during postlesion. In the contralateral side, most of regions examined showed no significant change in dopamine uptake sites, dopamine D1 receptors and dopamine D2 receptors during postlesion except for a transient change in a few regions. These results demonstrate that 6-hydroxydopamine can cause a severe functional damage in dopamine uptake sites in the striatum, SN and VTA. Our findings also suggest that the up-regulation in dopamine D2 receptors is more pronounced than that in dopamine D1 receptors in the brain after 6-hydroxydopamine treatment. Furthermore, our results support the existence of dopamine D2 receptors on the neurons of SN and VTA. Thus, our findings provide insights into the pathogenesis of Parkinson's disease.


Substrate inhibition and allosteric regulation by heparan sulfate of Trypanosoma brucei cathepsin L.
The cysteine protease brucipain is an important drug target in the protozoan Trypanosoma brucei, the causative agent of both Human African trypanosomiasis and Animal African trypanosomiasis. Brucipain is closely related to mammalian cathepsin L and currently used as a framework for the development of inhibitors that display anti-parasitic activity. We show that recombinant brucipain lacking the C-terminal extension undergoes inhibition by the substrate benzyloxycarbonyl-FR-7-amino-4-methylcoumarin at concentrations above the K(m), but not by benzyloxycarbonyl-VLR-7-amino-4-methylcoumarin. The allosteric modulation exerted by the substrate is controlled by temperature, being apparent at 25°C but concealed at 37°C. The behavior of the enzyme in vitro can be explained by discrete conformational changes caused by the shifts in temperature that render it less susceptible to substrate inhibition. Enzyme inhibition by the di-peptydyl substrate impaired the degradation of human fibrinogen at 25°C, but not at 37°C. We also found that heparan sulfate acts as a natural allosteric modulator of the enzyme through interactions that prevent substrate inhibition. We propose that brucipain shifts between an active and an inactive form as a result of temperature-dependent allosteric regulation.


Efficient photodegradation of cefixime catalyzed by a direct Z-scheme CQDs-BiOBr/CN composite: Performance, toxicity evaluation and photocatalytic mechanism.
Development of low-cost, nontoxic, highly efficient performance photocatalyst for water pollution control engineering is critical for environmental remediation. In this contribution, a direct Z-scheme heterojunction based on C quantum dot (CQDs), bismuth oxybromide (BiOBr) and bulk graphitic carbon nitride (g-C3N4, CN) (CQDs-BiOBr/CN composite) with outstanding photocatalytic activity and good reusability is successfully fabricated though a hydrothermal procedure for cefixime antibiotic photodegradation. In particular, the CQDs-BiOBr/CN composite possess the best cefixime degradation effect, the degradation rate is about 92.82% within 120 min. The enhancement photocatalytic activity of CQDs-BiOBr/CN can be ascribed to the improved light-harvest ability, the excellent adsorption performance, the efficient charge transportation and separation capability. A possible degradation pathway of cefixime is proposed base on HPLC-MS. Toxicity experiments demonstrate that the antibiotic activity of cefixime is effectively deactivated after degradation process, and which is no toxic effect for Rye seeds in deionized water. The CQDs-BiOBr/CN also displays the excellent photoactivation activity towards Escherichia coli (E. coli). Reactive-species-trapping experiments show that hydroxyl radical (⋅OH) and superoxide radical (⋅O2-) are the active reactive species in the photodegradation process. The CQDs-BiOBr/CN composite demonstrate an effective potential practical application in antibiotic pollutants degradation from wastewater.


Kinetics of l-5-hydroxytryptophan in healthy subjects.
The kinetics of l-5-hydroxytryptophan (5-HTP) were studied in five volunteers after intravenous and oral administration of 5-HTP following pretreatment with carbidopa. In addition, the effect of pretreatment with carbidopa on metabolism and disposition of 5-HTP was studied in eight subjects. The kinetics of 5-HTP following a 20-minute linear infusion are adequately described by a biexponential function. The biological half-life of 5-HTP ranged from 2.2 to 7.4 hours, and the plasma clearance ranged from 0.10 to 0.23 1/kg/hour. The bioavailability of 5-HTP after oral administration in combination with carbidopa was calculated as 48% +/- 15 (mean +/- SD). The plasma concentrations of 5-HTP observed in this study displayed an unusual double peak in most subjects after oral administration. Pretreatment with carbidopa caused a significant increase in the extent of absorption of unchanged 5-HTP, and a significant reduction in the area under the plasma concentration-time curves of 5-hydroxyindoleacetic acid. Gastrointestinal side effects appeared to be related to the 5-HTP plasma concentration.


Disseminated Pasteurella multocida infection: Cellulitis, osteomyelitis, and myositis.
A 67-year-old man with poorly controlled type II diabetes mellitus was evaluated for right lower extremity erythema and swelling and left-sided lower back pain. He was found to have Pasteurella multocida bacteremia; magnetic resonance imaging showed osteomyelitis of the lumbar spine with myositis in the adjacent left paraspinal muscles. He was initially treated with intravenous antibiotics and was later transitioned to oral amoxicillin. He recovered completely with six weeks of antimicrobial therapy.


Cyclic loading alters biomechanical properties and secretion of PGE2 and NO from tendon explants.
Tendon overuse injuries are a common occurrence; accounting for a large proportion of occupational and athletic injuries. The concept examined in this study is the role of load-induced intrinsic inflammation to the mechanism of these injuries. This study examined the influence of cyclical loading on the mechanical properties, cell viability, and inflammatory mediators of cultured tendon explants. Chicken digital flexor tendon explants were isolated and separated into no-load (24 h rest), moderate load (0.25-3.0 MPa, 1 Hz, 4 h, 20 h rest), and aggressive load (0.25-12.0 MPa, 1 Hz, 24 h) treatment groups. Tissue loading was carried out with a pneumatic device under load-control. The loading regimens for each explant treatment group started at a uniform time point (day 3 from isolation, t = 0 h). Medium was collected at t = 24 and t = 48 h and analyzed for the inflammatory mediators prostaglandin E(2) and nitric oxide. Viability was evaluated at t = 48 h. Biomechanical data revealed a significantly (P < 0.05) lower strength in the aggressively loaded specimens compared to the moderately loaded samples. Prostaglandin E(2) concentrations of aggressively loaded samples showed significantly higher values compared to moderately loaded samples at t = 48 h. Nitric oxide concentrations were greater in the moderately loaded samples relative to the no-load group at t = 24 h. Viability was not found to differ among the groups. Alterations in cyclical loading of tendon may cause a change in fibroblast-mediated inflammatory mediator production in tendon. This response is of clinical significance as it may have a role in the pathology of tendon overuse injuries.


Simultaneous photocatalytic removal of organic dye and heavy metal from textile wastewater over N-doped TiO2 on reduced graphene oxide.
Methylene blue (MB) and hexavalent chromium(Cr(VI)) are hazardous pollutants in textile waste and cannot be completely removed using conventional methods. So far, there have been no specific studies examining the synthesis and activity of N-TiO2/rGO as a photocatalyst for removing MB and Cr(VI) from textile wastewater. This work especially highlights the synthesis of N-TiO2/rGO as a photocatalyst which exhibits a wider range of light absorption and is highly effective for simultaneous removal of MB-Cr(VI) under visible light. Titanium tetrachloride (TiCl4) was used as the precursor for N-TiO2 synthesis using the sol-gel method. Graphite was oxidized using Hummer's method and reduced with hydrazine to produce rGO. N-TiO2/rGO was synthesized using a hydrothermal process and then analyzed using several characterization instruments. The X-ray diffraction pattern (XRD) showed that the anatase N-TiO2/rGO phase was detected at the diffraction peak of 2θ = 25.61. Scanning electron microscopy and transmission electron microscopy (SEM-EDS and TEM) dispersive X-ray spectrometry images show that N-TiO2 particles adhere to the surface of rGO with uniform size and N and Ti elements are present in the N-TiO2/rGO combined investigated. Gas absorption analysis data (GSA) shows that N-TiO2/rGO had a surface area of 77.449 m2/g, a pore volume of 0.335 cc/g, and a pore size of 8.655 nm. The thermogravimetric differential thermal analysis (TG-DTA) curve showed the anatase phase at 500-780 °C with a weight loss of 0.85%. The N-TiO2/rGO composite showed a good photocatalyst application. The photocatalytic activity of N-TiO2/rGO for textile wastewater treatment under visible light showed higher effectiveness than ultraviolet light, with 97.92% for MB and 97.48% for Cr(VI). Combining N-TiO2 with rGO is proven to increase the light coverage in the visible light region. Removal of MB and Cr(VI) can be carried out simultaneously and results in a removal efficiency of 95.96%.


Gastrocolic fistulae; From Haller till nowadays.
Gastrocolic Fistula is, in the majority of cases the pathological communication between stomach and transverse colon, because cases involved with the small intestine, pancreas and skin have been also documented, even though are rare. It occurs mostly in adults, but they can be present to infants, as well, as a result of congenital abnormalities or iatrogenic procedures (i.e. migration of PEG tube that placed before). In the Western Countries, the most common cause is the adenocarcinoma of the colon, while in Japan, adenocarcinoma of the stomach is the most frequent cause. It seldom appears, as a complication of a benign peptic ulcer, in Crohn's disease and as a result of significant intake of steroids or NSAIDs. The typical symptoms of a gastrocolic fistula are abdominal pain, nausea-vomiting, diarrhea and weight loss. Radiology has been used for the detection of the fistulae all these years but the golden standard remained the barium enema. Barium meal and CT findings play a smaller role in the diagnosis. Although the management of gastrocolic fistulae has historically been surgical, medical treatment has recently been recommended as the first line when a malignancy can be excluded.


[Cu3(mu-S)2]3+ clusters supported by N-donor ligands: progress toward a synthetic model of the catalytic site of nitrous oxide reductase.
By treating Cu(I) complexes of neutral, bidentate N-donor ligands with S8, clusters with novel delocalized mixed-valence [Cu3(mu-S)2]3+ cores have been isolated. X-ray crystal structures and UV-vis and resonance Raman spectral features of these clusters reveal similarities to the tetracopper-sulfide "CuZ" site in nitrous oxide reductase. A delocalized S = 1 ground state for the mixed-valent CuIIICu2II cores is supported by the observation of high symmetry in the X-ray structures and 10-line hyperfine features arising from coupling to three equivalent Cu ions in EPR spectra obtained at room temperature (shown) and 10 K. The delocalization we observe contrasts with the localization reported previously for a [Cu3(mu-O)2]3+ analogue (Root, D. E.; Henson, M. J.; Machonkin, T.; Mukherjee, P.; Stack, T. D. P.; Solomon, E. I. J. Am. Chem. Soc. 1998, 120, 4982), which we rationalized through DFT calculations.


HLA BW54 and B5 in Japanese diabetics with juvenile-onset and insulin-dependency (with special reference to the family history).
The frequency of HLA BW54 and B5 in Japanese patients with JOD is increased and decreased, respectively. In JOD patients without a family history of MOD, the frequency of BW54 is significantly increased, whereas in JOD patients with a positive family history the frequency was not increased in a statistically significant manner.


Auranofin: Past to Present, and repurposing.
Auranofin (AF), a gold compound, has been used to treat rheumatoid arthritis (RA) for more than 40 years; however, its mechanism of action remains unknown. We revealed that AF inhibited the induction of proinflammatory proteins and their mRNAs by the inflammatory stimulants, cyclooxygenase-2 and inducible nitric oxide synthase, and their upstream regulator, NF-κB. AF also activated the proteins peroxyredoxin-1, Kelch-like ECH-associated protein 1, and NF-E2-related factor 2, and inhibited thioredoxin reductase, all of which are involved in oxidative or electrophilic stress under physiological conditions. Although the cell membrane was previously considered to be permeable to AF because of its hydrophobicity, the mechanisms responsible for transporting AF into and out of cells as well as its effects on the uptake and excretion of other drugs have not yet been elucidated. Antibodies for cytokines have recently been employed in the treatment of RA, which has had an impact on the use of AF. Trials to repurpose AF as a risk-controlled agent to treat cancers or infectious diseases, including severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019, are ongoing. Novel gold compounds are also under development as anti-cancer and anti-infection agents.


Sexual dimorphism in the gills of the spawning river lamprey, Lampetra fluviatilis L.
Two types of mitochondria-rich cells were found in the interplatelet areas of the gills of sexually mature, male river lampreys. Type 1 cells (previolsy referred to as "male glandular cells") showed some ultrastructural characteristics in common with ion-transporting cells but were readily distinguished by large lipid structures with electron-lucent centres. Type 2 cells were found to be identical to the presumed ion-uptake cells during other stenohaline freshwater phases of the animal's life history. In the sexually mature female, only Type 2 cells were positively identified. This sexual dimorphism in gill structure is discussed in relation to the possible functions of the lamprey gill, with particular reference to ionic regulation.


Searching for camouflaged targets: effects of target-background similarity on visual search.
Do observers search for camouflaged targets by looking through the distractors or by scrutinizing the target-similar background? In four experiments observers searched for toy targets among distractors under varying set size and target-background similarity (TBS) conditions. Manual errors and RTs increased with TBS, although search slopes did not significantly differ. Eye movement analyses revealed that the majority of fixations fell on discrete distractors rather than on the target-similar background, even under high TBS conditions. These data suggest a biased search process; salient patterns segmented from a background are preferred while more target-similar unsegmented regions of the background are relatively neglected.


Alcohol interactions with lipids: a carbon-13 nuclear magnetic resonance study using butanol labeled at C-1.
The interactions of carbon-13 enriched butanol with dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were studied using C-13 nuclear magnetic resonance. It was found that above the gel to liquid crystal phase transition the resonance from the butanol could be resolved into two signals with similar chemical shifts but different T1 values and line widths. In contrast, only one narrow resonance was observed for ethanol, which has considerably less solubility in the lipids than butanol. Thermodynamic analyses of the effects of butanol on the phase transition temperature predict much greater solubility or butanol when the lipid is above the phase transition temperature than when it is below. It was concluded that the two butanol resonances represent two slowly exchanging populations, the free butanol in the aqueous phase and butanol dissolved in the liquid crystalline region of the lipid. No bound butanol was detected below the gel to liquid crystal phase transition. Relaxation studies were performed on the resonance of the bound butanol in DPPC and DMPC, including measurements of T1, line width, and nuclear Overhauser enhancement. Theoretical analysis of the relaxation parameters indicates that the lipid-bound alcohol has very high mobility within the fluid lipid bilayer. The data are consistent with butanol being present at the aqueous boundary or head group region of the lipid.


Inter-brain synchronization during coordination of speech rhythm in human-to-human social interaction.
Behavioral rhythms synchronize between humans for communication; however, the relationship of brain rhythm synchronization during speech rhythm synchronization between individuals remains unclear. Here, we conducted alternating speech tasks in which two subjects alternately pronounced letters of the alphabet during hyperscanning electroencephalography. Twenty pairs of subjects performed the task before and after each subject individually performed the task with a machine that pronounced letters at almost constant intervals. Speech rhythms were more likely to become synchronized in human-human tasks than human-machine tasks. Moreover, theta/alpha (6-12 Hz) amplitudes synchronized in the same temporal and lateral-parietal regions in each pair. Behavioral and inter-brain synchronizations were enhanced after human-machine tasks. These results indicate that inter-brain synchronizations are tightly linked to speech synchronizations between subjects. Furthermore, theta/alpha inter-brain synchronizations were also found in subjects while they observed human-machine tasks, which suggests that the inter-brain synchronization might reflect empathy for others' speech rhythms.


Differentiating unipolar and bipolar depression by alterations in large-scale brain networks.
Misdiagnosing bipolar depression can lead to very deleterious consequences of mistreatment. Although depressive symptoms may be similarly expressed in unipolar and bipolar disorder, changes in specific brain networks could be very distinct, being therefore informative markers for the differential diagnosis. We aimed to characterize specific alterations in candidate large-scale networks (frontoparietal, cingulo-opercular, and default mode) in symptomatic unipolar and bipolar patients using resting state fMRI, a cognitively low demanding paradigm ideal to investigate patients. Networks were selected after independent component analysis, compared across 40 patients acutely depressed (20 unipolar, 20 bipolar), and 20 controls well-matched for age, gender, and education levels, and alterations were correlated to clinical parameters. Despite comparable symptoms, patient groups were robustly differentiated by large-scale network alterations. Differences were driven in bipolar patients by increased functional connectivity in the frontoparietal network, a central executive and externally-oriented network. Conversely, unipolar patients presented increased functional connectivity in the default mode network, an introspective and self-referential network, as much as reduced connectivity of the cingulo-opercular network to default mode regions, a network involved in detecting the need to switch between internally and externally oriented demands. These findings were mostly unaffected by current medication, comorbidity, and structural changes. Moreover, network alterations in unipolar patients were significantly correlated to the number of depressive episodes. Unipolar and bipolar groups displaying similar symptomatology could be clearly distinguished by characteristic changes in large-scale networks, encouraging further investigation of network fingerprints for clinical use. Hum Brain Mapp 37:808-818, 2016. © 2015 Wiley Periodicals, Inc.


Novel media for chromatography and immobilization using a radiation grafting technique.
Radiation grafting onto polyamide and poly(vinyl alcohol) was performed using different vinyl monomers. This grafting technique permits the synthesis of carrier media with a wide range of physical and chemical properties. A number of immobilization tests with antibodies and enzymes e.g., penicillin acylase, glucose isomerase and formate dehydrogenase, are described, exhibiting binding capacities which are distinctly higher than those achieved with commercial media. The epoxy- and isocyanate-activated grafted copolymers were used for the affinity chromatographic separation of insulin, factor VIII and human serum albumin using antibodies as affinity ligands. The radiation-modified media allow a high antibody coupling, thus overcoming drawbacks of currently available commercial media. The separation of blood group antibodies can be performed by using novel antibody-specific oligosaccharide ligands, which permit a much more specific separation than protein G coupled media.


Synthesis and some characteristics of [13C]-specially enriched tetragastrin and the related compound.
[13C]-enriched tetragastrin and the related compound were synthesized in solution. Conversion of S-[13C]methylated tetragastrin to the enriched tetragastrin gave 10.5 ppm upfield chemical shift of Cepsilon resonance. The potency of the synthetic tetragastrin to stimulate gastric acid secretion was virtually identical with that of pentagastrin (ICI).


Effect of chia flour associated with high fat diet on intestinal health in female ovariectomized Wistar rats.
The present study aimed to evaluate the effect of chia flour associated with a high fat diet on intestinal health in female ovariectomized Wistar rats. The study was conducted with 32 adult female ovariectomized Wistar rats, which were separated into four groups: standard diet (ST), standard diet with chia (STC), high fat diet (HF) and high fat diet with chia (HFC) for 18 weeks. Cecum content pH, short chain fatty acid content, brush border membrane functionality and morphology and the gut microbiota were evaluated. This study demonstrated that the consumption of chia flour increased the production of acetic and butyric acids, the longitudinal and circular muscle layers and crypt thickness. It also improved the expression of aminopeptidase (AP) and sucrose-isomaltase (SI) and decreased the cecum content pH. Further, the consumption of chia improved richness and decreased diversity of the microbiota. Operational Taxonomic Units (OTUs) clustering indicated difference between the ST and STC groups. In the linear discriminant analysis effect size (LEfSe) analysis, the Bacteroides genus and members of the Muribaculaceae and Lachnospiraceae families were enriched in the STC treatment group. The STC group demonstrated the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways related to peptidoglycan and coenzyme A biosynthesis. Our results suggest that chia flour, which is rich in dietary fiber and phenolic compounds, presented potential properties to improve intestinal health.


Antitumor Properties of Curcumin in Breast Cancer Based on Preclinical Studies: A Systematic Review.
Breast cancer is one of the most common neoplasms among women. Anticancer strategies using natural formulations and phytotherapies are promising antitumor treatment alternatives. This review assesses the antitumor effects of curcumin on breast cancer reported in preclinical in vitro and in vivo animal models. We used five databases to search for preclinical studies published up to May 2021. The assessments included the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and on tumor volume. In total, 60 articles met the inclusion criteria. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells. Nanoparticle formulations of curcumin administered orally, via implant, and intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo. Moreover, curcumin nanoformulations exert positive effects on tumor growth inhibition in animal models of breast cancer. Further randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use.


Classic (Mediterranean) Kaposi's sarcoma of the true vocal cord: a case report and review of the literature.
Kaposi's sarcoma (KS) is a rare subcutaneous lesion linked mainly with patients suffering from acquired immunodeficiency syndrome. The aim of the present study is to present the first documented case of classic Kaposi's sarcoma (CKS) located in the right true vocal cord. A 62 year old male presented with cough and hoarseness for 2 months. Clinical examination revealed a nodule on the right vocal cord. The patient underwent surgery and the lesion was removed and biopsied. The histopathology report showed that the lesion was KS but with no complete removal of the lesion, since the surgical margins of the nodule were not healthy. The patient, although fully informed, refused any further treatment. Further laboratory tests were performed, revealing an HIV-negative immunodeficiency profile. Although (Mediterranean) CKS is not an aggressive malignancy, surgery with complete removal of the affected area is indicated when it is applicable. Moreover, conservative treatment and follow up of the patient is essential in order to prevent relapse or other primary lesions.


A new recurrent chromosomal translocation t(3;11)(q13;q14) in myelodysplastic syndromes associated with overexpression of the ILDR1 gene.
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the combination of conventional cytogenetic, FISH studies and molecular techniques allowed us to unveil a novel recurrent t(3;11)(q13;q14) causing the overexpression of the immunoglobulin-like domain-containing receptor (ILDR1) gene. The analysis of gene expression was extended to Refractory Anemia (RA) and Refractory Anemia with excess blasts (RAEB) cases revealing ILDR1 overexpression in 36% of RAEB subgroup. The biological implications of the ILDR1 overexpression in MDS pathogenesis and its potential prognostic significance should be further investigated.


Study protocol for the MEXiletine hydrochloride administration trial: a placebo-controlled, randomised, double-blind, multicentre, crossover study of its efficacy and safety in spinal and bulbar muscular atrophy (MEXPRESS).
Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive neuromuscular disease. Cold exposure often leads to worsening of motor symptoms including paresis. Although mexiletine hydrochloride administration has been shown to be effective for the treatment of several muscular diseases, its effectiveness in SBMA has not been validated to date. The trial will test it as a symptomatic drug for cold paresis. This study is the first trial to evaluate the efficacy and safety of mexiletine hydrochloride administration in patients with SBMA. A placebo-controlled, randomised, double-blind, multicentre, crossover clinical trial will be conducted to assess the safety and efficacy of mexiletine hydrochloride in patients with SBMA. The eligible patients will be assigned randomly in a 1:1 ratio to two groups in a double-blind manner. Participants will take mexiletine hydrochloride (300 mg/day) or a placebo orally three times a day for 4 weeks (period 1). After a 1-week washout period, participants will take the other drug for 4 weeks (period 2). The primary endpoint is the difference in distal latencies between room temperature and cold exposure conditions. This study will be conducted in compliance with the Helsinki Declaration and the Ethical Guidelines for Medical and Health Research Involving Human Subjects by the Japanese government and has been approved by the ethics committee of Nagoya University Graduate School of Medicine, as a central institutional review board, and by each facility. The results will be disseminated in peer-reviewed journals and at scientific conferences. UMIN000026150; Pre-results.


Neonatal seizures: characteristics of EEG ictal activity in preterm and fullterm infants.
The neonatal EEG remains one of oldest, yet most valuable, diagnostic and prognostic tests in neonates. The goals of this study were to determine the relationships between the morphology, frequency, and distribution of ictal discharges in the neonatal EEG with age, EEG background activity, and etiology. A total of 156 ictal events were evaluated in 11 preterm (PT) and 25 fullterm (FT) infants. Most of the infants had severe abnormalities of background activity although ictal discharges occurred on both normal and abnormal backgrounds. There was a trend for a closer relationship between behavioral changes during the electroencephalographic seizure when the background activity was normal or moderately abnormal than when background activity was severely abnormal. In both PT and FT infants, the most common site of seizure origin was the temporal lobe. FT infants commonly had sharp waves, spikes, sharp and slow waves, and spike and slow waves at the onset of the ictus while rhythmic delta activity was most common in the PT infants. PT infants typically had a regional onset to the ictus whereas FT infants most frequently had a focal onset. Duration of the ictal events was similar in PT and FT infants and a change in morphology or frequency of the discharges was common during propagation of the ictal discharges in both age groups. There was not a clear relationship between onset, morphology, frequency, or propagation patterns and etiology in either the PT or FT infants. Our results demonstrate that while the type of ictal discharge is related to gestational age, there is a rich variety in the onset, morphology, and frequency of the ictal discharges in both PT and FT infants and that neonatal ictal patterns lack a close correlation with underlying pathology.


Localized iron supply triggers lateral root elongation in Arabidopsis by altering the AUX1-mediated auxin distribution.
Root system architecture depends on nutrient availability, which shapes primary and lateral root development in a nutrient-specific manner. To better understand how nutrient signals are integrated into root developmental programs, we investigated the morphological response of Arabidopsis thaliana roots to iron (Fe). Relative to a homogeneous supply, localized Fe supply in horizontally separated agar plates doubled lateral root length without having a differential effect on lateral root number. In the Fe uptake-defective mutant iron-regulated transporter1 (irt1), lateral root development was severely repressed, but a requirement for IRT1 could be circumvented by Fe application to shoots, indicating that symplastic Fe triggered the local elongation of lateral roots. The Fe-stimulated emergence of lateral root primordia and root cell elongation depended on the rootward auxin stream and was accompanied by a higher activity of the auxin reporter DR5-β-glucuronidase in lateral root apices. A crucial role of the auxin transporter AUXIN RESISTANT1 (AUX1) in Fe-triggered lateral root elongation was indicated by Fe-responsive AUX1 promoter activities in lateral root apices and by the failure of the aux1-T mutant to elongate lateral roots into Fe-enriched agar patches. We conclude that a local symplastic Fe gradient in lateral roots upregulates AUX1 to accumulate auxin in lateral root apices as a prerequisite for lateral root elongation.


Clinical and cerebrospinal fluid (CSF) profile and CSF criteria for the diagnosis of spinal cord schistosomiasis.
To describe the clinical and CSF findings among patients with presumptive neuroschistosomiasis (NS) and to suggest a classification for the CSF diagnosis of presumptive NS. The charts of all patients whose CSF exam was performed at the CSF Lab, Jos Silveira Foundation, Salvador, Brazil, from 1988 to 2002 were reviewed. Those with clinically suspected NS whose indirect fluorescent antibody test (IFA) and or hemagglutination-inhibiting antibodies test (HAI) were positive to S. mansoni were identified. Of 377 patients, 67.9% were males; the median age was 36 years (mean 37 + 16 yrs, range 3-82 yrs). The most frequent complaints were paraparesis (59.9%), urinary retention (36.2%), lower limb pain (22.8%). WBC of CSF (count/mm ) was > 4 in 66.0% (mean 83 + 124, median 40, range 4.3-1,100), protein (mg/dl) was > 40 in 84.6% (mean 185 + 519, median 81, range 41-6,800) and eosinophils were present in 46.9%. IFA and HAI were positive in 75.3%. WBC > 4 and presence of eosinophils were associated with IFA and HAI positive (67.3% versus 51.4%, p 0.014; 49.1% versus 23.0%, p 0.0001, respectively) and protein > 40 was not (85.4% versus 77.0%, p 0.09). Presence of WBC > 4, protein > 40 and eosinophils was associated with IFA and HAI positive (71.6% versus 38.2%, p 0.0003) but presence of eosinophils and any other combination of WBC and protein were not. NS should be considered as a possible diagnosis in patients who had had contact with schistosome-infected water and present with spinal cord compromising. Presence of IFA and HAI positive to S. mansoni, WBC > 4, protein > 40 and presence of eosinophils in the CSF may be considered as a criterium of highly probable presumptive diagnosis.


Health-related quality of life among people with epilepsy with mild seizure-related head injuries.
Seizure-related head injury (SRHI) is an under-recognized condition frequently experienced by people with epilepsy (PWE). The purpose of this study is to investigate the potential impact of SRHI on health-related quality of life (HRQOL) among PWE receiving care in a tertiary epilepsy center. Consecutive adult PWE receiving care at the Baylor Comprehensive Epilepsy Center (BCEC) were recruited for the study. After their informed consent was obtained, patients were administered the QOLIE-31 to measure HRQOL and the NDDI-E to screen for depression. Simple linear regression was used to identify clinical variables associated with HRQOL and that included SRHI obtained systematically at each clinic visit. Data were also compared between the SRHI and non-SRHI groups. Participants included 172 subjects. Recurrent mild SRHI occurred in 50 (29%) subjects. Factors with a negative effect on HRQOL included depression (slope=-19.99 [95% CI -25.16, -14.81]; p<.0001), recurrent SRHI (-17.02 [-22.35, -11.69]; p<.0001), past SRHI (-13.46 [-18.43, -8.48]; p<.0001), and seizure frequency (-0.17 [-0.26, -0.07]; p=0.001) on univariate analysis. With stepwise multiple regression, depression and recurrent SRHI significantly impacted HRQOL with slopes (95% CI; p-value) of (-17.53 [-22.34, -12.73]; p<.0001) and (-14.03 [-18.78, -9.28]; p<.0001), respectively. Patient-derived HRQOL is negatively associated with depression and recurrent SRHI, independently. There has been a justifiable increased awareness of the potential effects of head injuries among healthy individuals. Our data suggest that head injuries can certainly be detrimental among PWE, and greater efforts should be made to recognize and formulate prevention strategies for SRHI.


Antibodies against the folding domain of histone H5 cross-react with H1(0) but not with H1.
Antibodies to the folding domain (residues 22-100) of histone H5 were elicited in rabbits. Analysis of the specificity of these antibodies by enzyme-linked immunoassay and by diazobenzyloxymethyl cellulose transfer techniques revealed that the antibody cross-reacts strongly with intact H5 and histones H1(0)a and H1(0)b purified from ox liver but not with the four core calf thymus, or with high mobility group proteins. We conclude that the globular region of H5 is serologically homologous to that of H1 degrees and suggest that possible functional similarities between the two proteins reside in this region.


Interaction between ambient particles and ozone and its effect on daily mortality.
To examine the effect of particulate matter (PM) less than 10 microns in diameter (PM10) and ozone (O3) on daily mortality in Shanghai, China. A generalized additive model with penalized spline function was used to observe the acute effect of PM10 and O3 on daily mortality. Higher PM10 significantly increased the effect of O3 on total mortality, and O3 also increased the effect of PM10 although the estimated increment was statistically insignificant. Our findings provide further evidence for the effect of PM10 and O3 on daily mortality.


Modulation of network centrality and gray matter microstructure using multi-session brain stimulation and memory training.
Neural mechanisms of behavioral improvement induced by repeated transcranial direct current stimulation (tDCS) combined with cognitive training are yet unclear. Previously, we reported behavioral effects of a 3-day visuospatial memory training with concurrent anodal tDCS over the right temporoparietal cortex in older adults. To investigate intervention-induced neural alterations we here used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) datasets available from 35 participants of this previous study, acquired before and after the intervention. To delineate changes in whole-brain functional network architecture, we employed eigenvector centrality mapping. Gray matter alterations were analyzed using DTI-derived mean diffusivity (MD). Network centrality in the bilateral posterior temporooccipital cortex was reduced after anodal compared to sham stimulation. This focal effect is indicative of decreased functional connectivity of the brain region underneath the anodal electrode and its left-hemispheric homolog with other "relevant" (i.e., highly connected) brain regions, thereby providing evidence for reorganizational processes within the brain's network architecture. Examining local MD changes in these clusters, an interaction between stimulation condition and training success indicated a decrease of MD in the right (stimulated) temporooccipital cluster in individuals who showed superior behavioral training benefits. Using a data-driven whole-brain network approach, we provide evidence for targeted neuromodulatory effects of a combined tDCS-and-training intervention. We show for the first time that gray matter alterations of microstructure (assessed by DTI-derived MD) may be involved in tDCS-enhanced cognitive training. Increased knowledge on how combined interventions modulate neural networks in older adults, will help the development of specific therapeutic interventions against age-associated cognitive decline.


Cystic Fibrosis and gastroesophageal reflux disease.
Gastroesophageal reflux is common in children and adults with cystic fibrosis (CF). Pathological gastroesophageal reflux disease (GERD) is also frequent in patients of all ages with CF. This article reviews the pathophysiology, diagnostic work-up, management options, complications, and future directions in the evaluation and management of GERD - unique to and pertinent for - patients with CF in particular.


Clinical case management of revolving door patients - a semi-randomized study.
To assess the effectiveness of psychiatric clinical case management. Subjects with at least three admissions in the previous 2 years were randomized into a clinical case management group (CMG; n = 122) and a standard care group (SCG; n = 95). Individuals who refused or were not located were included in a third, non-randomized no-treatment group (NTG; n = 153). Parameters assessed included utilization of in-patient services and psychosocial functioning. We found no difference between the CMG and the SCG in psychosocial functioning as evaluated by interviewers, and no difference between the three groups in hospitalization. In subjects' self-ratings, the CMG showed slight improvement in psychosocial functioning. Clinical case management did not prove itself superior to standard care in a revolving door population.


Wettability of root canal sealers on intraradicular dentine treated with different irrigating solutions.
The aim of this in vitro study was to evaluate the wettability of AH Plus and ThermaSeal Plus sealers on intraradicular dentine treated with different irrigating solutions. Fifty anterior teeth were decoronated and split longitudinally. Each root half was divided into 5 groups (n=10). Group I: 5mL of 2.5% NaOCl+QMix. Group II: 5mL of 2.5% NaOCl+17% EDTA. Group III: 5mL of 2.5% NaOCl+7% maleic acid. Group IV: 5mL of 2.5% NaOCl. Group V: 5mL of distilled water. Irrigation regimens were performed for 1min. Each specimen was placed inside a Dynamic Contact Angle Analyser. A controlled-volume droplet of sealer was placed on each specimen and the static contact angle was analysed. The contact angle made by both sealers with EDTA-irrigated dentine was significantly larger when compared to the other irrigants (P<0.05). For ThermaSeal Plus, contact angles produced on maleic acid-, NaOCl- and distilled water-irrigated dentine were not significantly different, but were all significantly larger than the contact angle produced on QMix-irrigated dentine (P<0.05). For AH Plus, contact angles produced on NaOCl- and distilled water-irrigated dentine were not significantly different, but were significantly larger than those made by maleic acid and QMix. When used as a final irrigant, QMix favours the wetting of root canal dentine by both AH Plus and ThermaSeal Plus sealers. Maleic acid shows a promising result when compared to EDTA and NaOCl. Wettability of both sealers is the worst on EDTA-irrigated dentine. The present study highlights the effect of newer endodontic irrigating solutions on the wettability of sealers on to the root canal dentine, which is required for obtaining good obturation seal.


Antioxidant effect of two flavonoids from the bark of Ficus bengalensis Linn in hyperlipidemic rats.
Two flavonoid compounds, viz. 5,7-dimethyl ether of leucopelargonidin 3-0-alpha-L rhamnoside and 5,3'-dimethyl ether of leucocyanidin 3-0-alpha-D galactosyl cellobioside obtained from the bark of F. bengalensis were evaluated for their antioxidant action in hyperlipidemic rats. The results were compared with the activity of a structurally similar flavonoid, quercetin, a known antioxidant. The Ficus compounds showed significant antioxidant effects which may be attributed to their polyphenolic nature. The methylation of two hydrozyl groups in the Ficus flavonoids might have slowed down their antioxidant action as compared to quercetin.


Transjugular Intrahepatic Portosystemic Shunt Creation Using a Radiofrequency Wire: Acute Feasibility Study in Swine.
The feasibility of a radiofrequency (RF) wire to replace the needle trocar for the creation of a transjugular intrahepatic portosystemic shunt (TIPS) was assessed in 3 swine by using fluoroscopy and intravascular ultrasonography (IVUS). RF wire passes were successful from hepatic to portal vein and from inferior vena cava to portal vein. Technical success was achieved using both IVUS guidance and carbon dioxide portography. The wire tracked a straight course under RF energy application without subjective deflection and, when centrally advanced, served as the working wire for completing the TIPS in 2 attempts with stent graft deployment. No procedural adverse events from the use of RF wire were observed.


Saline washout for knee osteoarthritis: results of a controlled study.
Twenty patients with persistent symptoms due to osteoarthritis of the knee were randomly allocated to a saline washout or control group. Both groups showed improvement. Knee washout conferred no more benefit than intra-articular saline injection.


Large-scale management systems and parasite populations: coccidia in rabbits.
Broiler rabbit production has become an important branch of animal protein and fur production, not only in the traditionally rabbit breeding and consuming countries, but recently in many other countries of the world. The profitability of the rabbit industry is dependent primarily on the good feed conversion. Aspects of this include factors such as morbidity and mortality of infections, adequate knowledge and fulfilment of both accommodation and nutritional requirements, appropriate breeding systems, etc. There is much controversy about the role of coccidia in the losses of intensified rabbit breeding enterprises. There is no doubt about the significance of Eimeria stiedai which may cause condemnation of large amounts of liver as a result of infection in rabbit colonies of small holders. However, this parasite is rare in large scale rabbit farms. In the latter, intestinal coccidiosis is most frequently--although not invariably--incriminated either as a primary or more often as a predisposing factor of intestinal enteropathies causing severe mortality, mainly in the early post-weaning period. The ability to isolate and maintain species of Eimeria in specific pathogen-free (SPF) rabbits has made it possible to characterize them, such as the most pathogenic E. intestinalis and E. flavescens: the pathogenic E. magna, E. irresidua and E. piriformis; and the least pathogenic E. perforans, E. neoleporis (syn. of E. coecicola) and E. media species. Prophylactic measures are dealt with briefly, and laboratory and field trials with the currently most promising rabbit anti-coccidial drugs (Lerbek, robenidine and salinomycin) are dealt with in more detail.


Longitudinal gray matter change in young people who are at enhanced risk of schizophrenia due to intellectual impairment.
Existing studies of brain structural changes before the onset of schizophrenia have considered individuals with either familial risk factors or prodromal symptomatology. We aimed to determine whether findings from these studies are also applicable to those at enhanced risk of developing schizophrenia for another reason-intellectual impairment. Participants with intellectual impairment (mean IQ: 78.2) received magnetic resonance imaging of the brain at baseline (mean age: 16 years old) and again 6 years later. The Positive and Negative Syndrome Scale was used to assess psychotic symptoms. Participants were dichotomized using their Positive and Negative Syndrome Scale scores at follow-up and gray matter changes were compared between the groups using tensor based morphometry and semiautomated region of interest analysis. Forty-six individuals had scans of sufficient quality to be included in the study. The tensor based morphometry analyses revealed that those with psychotic symptoms at follow-up showed significantly greater gray matter reductions over 6 years in the medial temporal lobes bilaterally. Region of interest analyses revealed that those individuals with psychotic symptoms at follow-up showed a reduced right hippocampal volume at age 16 and reduced bilateral hippocampal volumes at follow-up. This unique study of individuals vulnerable to schizophrenia due to intellectual impairment highlights aberrant development in the medial temporal lobe associated with the occurrence of psychotic symptoms. These developmental changes are also evident in populations at enhanced risk of schizophrenia for familial and symptomatic reasons, suggesting they are central to the development of the disorder regardless of the nature of the vulnerability state.


Pharmaceuticals removal in an on-farm pig slurry treatment plant based on solid-liquid separation and nitrification-denitrification systems.
The fate and degradation of 28 multiple-class veterinary pharmaceuticals in an on-farm pig slurry treatment plant based on solid-liquid separation and a nitrification-denitrification (NDN) sequence batch reactor (SBR) were evaluated for the first time. The pharmaceuticals detected at the highest concentrations in raw pig slurries belonged to the group of tetracycline antibiotics. Fluoroquinolone, lincosamide and pleuromutilin antibiotics and other drugs such as flubendazole and flunixin were also frequently detected. After solid-liquid separation, target compounds were distributed in an average of 64% onto the liquid fraction. Pharmaceuticals distributed in this fraction were removed in an average of almost 50% after being treated in NDN-SBR. Lincomycin was the compound with the highest removal percentage, reaching 100% reduction, while tetracyclines and fluoroquinolones showed moderate removal percentages (50 and 40%, respectively). Regarding nitrogen removal, NDN-SBR reduced a 77% of the content of this nutrient in the liquid slurry fraction.


Application of Hi-throat/Hi-volume SPE technique in assessing organophosphorus pesticides and their degradation products in surface water from Tai Lake, east China.
Organophosphorus pesticides (OPPs) are among the most commonly used pesticides worldwide. However, these compounds pose a serious threat to aquatic environments. Here, thirty-seven pesticides and eight degradation products were determined in surface water samples from Tai Lake, East China, using a high-volume solid phase extraction technique (Hi-throat/Hi-volume SPE). Surface water was pumped in-situ through a portable sampler, and OPPs in the water retained on the Hi-volume SPE adsorption column, finally extracted for analysis. This technique efficiently reduced the detection limits to below 0.3 ng/L. In total, 40 out of 45 OPP congeners were detected, which far exceeded the amount of OPPs in previous studies. The total concentration of OPPs ranged between 101.4 and 1530 ng/L (median: 378.9 ng/L). Parathion exhibited the highest concentration (median: 112.0 ng/L), followed by paraoxon-methyl (median: 90.3 ng/L), as well as carbophenothion, fenthion, and mevinphos. Agricultural areas were more polluted than residential and industrial regions. However, degradation products persisted in residential and industrial waters. The ecological risks of OPPs in these areas were estimated based on the risk quotient index (RQ). Parathion, fenthion, carbophenothion, and tolclofos-methyl occurred at high-risk levels, and the levels of degradation products were also non-trivial. Our findings thus indicated that OPP degradation products pose a potential threat to natural environments and should therefore be closely monitored.


The placental growth factor as a target against hepatocellular carcinoma in a diethylnitrosamine-induced mouse model.
The placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages, and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. We assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF knockout mice and monoclonal anti-PlGF antibodies in a mouse model for HCC. In addition, the effect of PlGF antibodies is compared to that of sorafenib, as well as the combination of both therapies. We have found that both in a transgenic knockout model and in a treatment model, targeting PlGF significantly decreases tumor burden. This was achieved not only by inhibiting neovascularisation, but also by decreasing hepatic macrophage recruitment and by normalising the remaining blood vessels, thereby decreasing hypoxia and reducing the prometastatic potential of HCC. Considering the favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, PlGF inhibition could become a valuable therapeutic strategy against HCC.


Differential regulation of the β-adrenoceptor density and cyclic AMP level with age and sex in turkey cardiac chambers.
Decreased responses of the heart to β-adrenoceptor stimulation with aging have been shown to occur merely in selected heart chambers in relation to increased catecholamine levels. However, there are no systematic studies that investigate all cardiac chambers with regard to receptor density and cAMP (adenosine 3', 5'-cyclic monophosphate) responses. We used meat-type turkey poults (British United Turkey (B.U.T.) Big 6) with increasing age because their heart seems to decrease in weight in relation to body weight and they are often used as an animal model for heart failure. The receptor density and distribution were quantified by radioligand binding analysis using (-)-[(125)I]-iodocyanopindolol and β-adrenoceptor subtype-specific antagonists (ICI 118.551 and CGP 20712 A) in membranes of four cardiac chambers (right and left atria and ventricles) of 6-week-, 12-week-, 16/21-week-, and 57-week-old B.U.T. BIG 6 turkeys. Receptor function was determined by measuring basal and stimulated cAMP production. In both sexes, the β-adrenoceptor density decreased significantly in all chambers with age without altered β-adrenoceptor subtype distribution. The receptor affinity (KD) to the radioligand was similar in hearts of all age groups. β-adrenoceptor-(isoproterenol and guanosine 5'-triphosphate), G-protein-(NaF) and catalytic unit of adenylate cyclase (forskolin, Mn(2+)) mediated cAMP responses were not chamber-dependent. Indeed, the cAMP level was significantly lower in 57-week-old hearts than in 6-week-, 12-week-, 16/21-week-old hearts. These data suggest that with increasing age and body weight, the β-adrenoceptor signal transduction pathway was highly blunted in all cardiac chambers, occurring by decreased receptor density and cAMP responses.


Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients.
We assessed the effects of a novel lipid emulsion with reduced content of n-6 fatty acids (FA), increased share of MUFA and n-3 FA and supplemental vitamin E on fatty acid and leukotriene pattern in surgical patients. In a double-blind, randomized study 33 patients received isonitrogenous, isocaloric TPN over 5 postoperative days following major abdominal surgery. 19 patients received the new SMOFlipid 20% and 14 patients a standard soybean oil emulsion (Lipovenoes 20%, both Fresenius Kabi), each 1.5 g fat/kg body weight (BW)/d. Routine lipid biochemistry, plasma tocopherol, fatty acid pattern in plasma phospholipids, as well as leukotriene (LT) release in leukocytes were assessed. Additionally, fatty acid pattern in leukocyte and platelet phospholipids were analysed, but results are not presented. On day 6, plasma alpha-tocopherol (34.2 +/- 10.3 vs. 17.6 +/- 2.9 micromol/L) and, in plasma PL, total n-3 FA were higher (11.1 +/- 1.9 vs. 4.9 +/- 0.9 mol%; p < 0.05) and total n-6 FA lower (23.8 +/- 2.2 vs. 31.8 +/- 1.7 mol%; P < 0.05); the ratio n-3/n-6 FA being elevated (0.5 +/- 0.1 vs. 0.2 +/- 0.0 p < 0.05) with SMOFlipid compared to the soybean oil emulsion. The shares of EPA (3.3+/-1.0 vs. 0.4+/-0.2 mol%; p<0.05) and DHA (6.9 +/- 1.8 vs. 3.7 +/- 0.8 mol%; p < 0.05) were highly increased but that of arachidonic acid (AA) was unchanged with SMOFlipid while the ratio EPA/AA was increased (0.7 +/- 0.2 vs. 0.1 +/- 0.0 p < 0.05). LTB(5) release was enhanced on day 6 (8.1 +/- 5.3 vs. 1.8 +/- 3.8 pmol/10(7) PMN, p < 0.05) and liberation of LTB(4) was lowered, yet not significantly with SMOFlipid (124.0 +/- 51.2 vs. 152.1 +/- 68.8 pmol/10(7) PMN). Length of hospital stay was significantly shorter with SMOFlipid (13.4 +/- 2.0 vs. 20.4 +/- 10.0 days, p < 0.05). Treatment with the new emulsion SMOFlipid is well tolerated and modulates FA and leukotriene pattern suggesting favourable anti-inflammatory effects and further clinical benefits.


Comparison of risk factors in acute myocardial infarction and unstable angina pectoris in patients < or =66 versus >66 years of age.
A prospective study was conducted of the differences in clinical characteristics between patients with acute myocardial infarction and those with unstable angina pectoris admitted to hospitals in the South-Osaka district of Japan. Gender and smoking were identified as discriminant risk factors for the incidence of acute myocardial infarction in patients < or =66 years with acute coronary syndromes; however, age alone affected the mode of presentation in older patients.


Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.
Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants--including variants that do not reach genome-wide significance--often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).


Elastic recovery in roll compaction simulation.
Roll compaction/dry granulation is a widely used granulation method in the pharmaceutical industry. The simulation of the process is of great interest, especially in the early phase of formulation development of solid dosage forms. The hybrid modeling approach allows to predict the roll compaction process parameters to produce ribbons with a desired solid fraction. Based on the process parameters, compacts (ribblets) of the same solid fraction are produced on a single punch press. So far, the prediction accuracy for the solid fraction of the ribbons was not satisfactory. It was found that the lack in prediction accuracy was due to the elastic recovery, which was not considered in the model. In this study, the fast in-die and the slow out-of-die elastic recovery of different excipients with varying compaction properties were investigated. A method was established to compensate for the elastic recovery of compacts in roll compaction simulation and to improve the prediction accuracy of the solid fraction considerably. The results were successfully implemented into the model through an additional learning step. Moreover, the findings were transferred to the mimicking of an API containing formulation. By modeling, it was possible to accurately predict the process settings to obtain ribbons with the desired solid fraction using only a small amount of material.


Testosterone deficiency accelerates early stage atherosclerosis in miniature pigs fed a high-fat and high-cholesterol diet: urine 1H NMR metabolomics targeted analysis.
To gain insights into the role of testosterone in the development of atherosclerosis and its related metabolic pathways, we applied a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach to investigate urine metabolic profiles in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM) and castrated male pigs with testosterone replacement (CMT). Our results showed that testosterone deficiency significantly increased atherosclerotic lesion areas, intima-media thickness, as well as serum lipid levels in the CM pigs. Moreover, seventeen significantly changed metabolites were identified in both IM vs. CM and CMT vs. CM groups. Among these, seven were shared between the two comparative groups and were all significantly reduced in the urine of the CM group but rescued in the CMT group. In addition, the correlation analysis demonstrated that several metabolites, including niacinamide, myo-inositol, choline and 3-hydroxyisovalerate, were negatively correlated with atherosclerotic lesion areas. Our study demonstrated that testosterone deficiency accelerated early AS formation in HFC diet-fed pigs, which involved several metabolites predominantly related to lipid metabolism, inflammation, oxidative stress and endothelial disorders. Our results reveal potential pathways in the pathogenesis of atherosclerosis caused by testosterone deficiency and HFC diet.


Hypertrophy of labia minora in myelodysplastic women. Labioplasty to ease clean intermittent catheterization.
Female myelodysplastic patients are sometimes annoyed by hypertrophy of the labia minora, possibly caused by long-term diaper dermatitis. This condition makes intermittent catheterization difficult and impairs the cleanliness and aesthetic appearance of the external genitalia. We successfully performed labioplasty on 3 myelodysplastic females.


Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors.
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs). Additionally, epithelial-mesenchymal transition (EMT)-related genes were found to be upregulated only in the CAF subpopulation of tumor samples. Notably, colorectal tumors previously assigned to a single subtype on the basis of bulk transcriptomics could be divided into subgroups with divergent survival probability by using single-cell signatures, thus underscoring the prognostic value of our approach. Overall, our results demonstrate that unbiased single-cell RNA-seq profiling of tumor and matched normal samples provides a unique opportunity to characterize aberrant cell states within a tumor.


delta pH-induced fluorescence quenching of 9-aminoacridine in lipid vesicles is due to excimer formation at the membrane.
The fluorescence of 9-aminoacridine (9-AA) is quenched in vesicular suspensions containing negatively charged lipid headgroups (e.g., phosphatidylserine) upon imposition of a transmembrane (inside acidic) pH-gradient. It is shown that this fluorescence loss is accompanied by the formation of 9-AA dimers that undergo a transition in the dimer excited state to a dimer-excimer state. This result has been obtained on the basis of the specific dimer fluorescence excitation and hypochromic absorbance spectra that are redshifted by maximally 275 cm-1 (4.4 nm) with respect to the corresponding monomer spectra, as well as by the detection of the characteristic broad excimer emission band, centered at 560 nm. The existence of the spectrally distinct dimer-excimer is further corroborated by fluorescence life-time measurements that indicate an increased lifetime of up to 24 ns for this complex as compared with the normal monomer fluorescence lifetime of 16 ns. The formation of this dimer-excimer complex from the monomers can be reversed completely and the original monomeric spectral properties restored after the abolishment of the electrochemical proton gradient. In addition to the delta pH-induced dimer redshift in absorbance and fluorescence excitation, a further small redshift in monomer absorbance, fluorescence excitation, and emission spectra is observed due solely to the presence of the negatively charged phospholipid headgroups.


Analysis of stromal mucin in oral epithelial dysplasia & oral squamous cell carcinoma- A histochemical study.
Mucins are glycoproteins that act as a selective molecular barrier and its alterations usually accompany the carcinogenesis. To evaluate the transition of mucins in the grades of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) using histochemical stains. A total of 66 samples of variable grades of OED and OSCC and each section was stained with PAS, Alcian blue- PAS (AB-PAS) and Aldehyde fuschin - Alcian blue (AF-AB). Mucins pattern and intensity were examined at 5 randomly selected fields on 10x magnification. 1. PAS stain - Predominantly OED and OSCC showed a diffuse pattern with a gradual decrease in intensity in OED and overall a weak intensity in OSCC. 2. AB-PAS stain - Neutral mucins showed gradual increase in its intensity in grades of OED and OSCC with no predominant pattern. The intensity for the acid mucins remains weak in all the grades of OED and OSCC with diffuse distribution, except in higher grades of OED and OSCC. 3. AF- AB stain - For sulphated mucins, in OED a focal and diffuse pattern was observed in OSCC with minimal intensity. The carboxylated mucin was absent in both. Mucins undergo change in its pattern and intensity in varying grades of OED/OSCC. Although in GIT and other mucosa, the expression of altered mucin is a recognized factor, seldom research has been done in OED and OSCC. Thus, the present study could be the stepping stone in the exploration of mucinous alteration in OED and OSCC.


Light and electron microscopic studies of a case with simultaneous Mondini and Michel deformities of the inner ears.
We performed light and electron microscopic studies on the temporal bones of a patient with genetic aplastic deafness, in which the right ear had a Mondini-type defect and the left ear a Michel-type anomaly. The round window of each ear was absent. The stapedial foot plate of the right ear was depressed at its central part and was covered by thin membrane. The course of the internal auditory meatus of the left ear was deviated ventrally. There was total aplasia of the cochlea in the left ear, while that of the right ear showed only three-quarters of a turn. In this ear, three sites of spherical bulging were found and were believed to represent outer hair cells. Other structures of the normal cochlear duct were not present. The modiolus of the left ear was round and dome-shaped, contained sparse nerve fibers and a primitive spiral ganglion. The saccule, utricle and semicircular canals of each ear were missing, so that a common cavity of the vestibular system was present. Several otoliths could be seen under the surface of the membrane covering the common cavity. No sensory cells or their related tissues could be found in either ear.


Cardiometabolic risk: a Framingham perspective.
To review published data on vascular disease- and diabetes-related outcomes related to adiposity and metabolic risk factors. Community cohort study with cross-sectional and prospective data. Middle-aged Caucasian adults in a suburban environment. Traditional risk factors for cardiovascular disease and the type 2 diabetes mellitus, as well as measures of insulin resistance, left ventricular hypertrophy and vascular calcification. The cardiometabolic risk factors cluster in the population and a common core that includes adiposity (both waist and body mass index), abnormal lipids (both HDL cholesterol and triglycerides), and abnormal glucose and insulin metabolism was found to be present in Framingham participants. Increased insulin resistance was also found to be associated with coronary artery calcification and left ventricular hypertrophy in women. Analyses of the metabolic syndrome risk factors showed that a greater burden of risk factors was associated with greater risk of both cardiovascular disease and diabetes mellitus. An equation to estimate risk of developing type 2 diabetes mellitus has been developed from the Framingham experience, and the risk factors included in the metabolic syndrome are key components, including increased waist girth, elevated blood pressure, low HDL cholesterol, high triglycerides and impaired fasting glucose. Cardiometabolic factors and insulin resistance are important contributors to the development of type 2 diabetes mellitus, subclinical cardiovascular disease and clinical cardiovascular disease.


Color removal from secondary treated pulp & paper industry effluent using waste driven Fe-TiO2 composite.
In the present study, the concurrent fixed-bed dual technology (photocatalysis and photo-Fenton) was performed as a polishing step for the color removal of tertiary treated agro-based paper & pulp industry effluent. For this purpose, the cheap and visibly dynamic Fe-TiO2 composite was prepared using industrial waste materials which also promoted the idea of the circular economy. The effectiveness of the prepared composite and the dual process was evaluated in terms of color removal efficiency and rate constant along with optimizing the process factors. Various kinetic models namely Log-linear, Weibull, and Biphasic with shoulder were used for the comparative study of three different processes i.e. photocatalysis, photo-Fenton, and dual process. Several parameters such as pH (4.5), % surface area covered (100%), and H2O2 dose (525 mgL-1) were optimized which gave the best output using dual-process i.e. 91.6% of color reduction along with good R2 values i.e. 0.874, 0.981 and, 0.998 for Log-linear, Weibull and, Biphasic with Shoulder model respectively. The proposed composite was durable enough to retain its dual catalytic ability with minor activity reduction of 5-10% even after 50 recycles. Thus, this innovative technology with the dual effect of photocatalysis and photo-Fenton can be a potential bet as a tertiary treatment option in the existing industrial wastewater treatment system for removing color from the final treated effluent.


At room temperature in water: efficient hydrogenation of furfural to furfuryl alcohol with a Pt/SiC-C catalyst.
Selective hydrogenation of furfural (FAL) to furfuryl alcohol (FOL) is challenging because of many side reactions. The highly selective hydrogenation of FAL to FOL can be achieved over a Pt catalyst supported on nanoporous SiC-C composites even at room temperature in water. A Pt/SiC-C-200-H2 catalyst, which had a Pt loading of 3 wt% and was reduced in flowing hydrogen at 500 °C after calcination in air at 200 °C for 2 h, furnished complete FAL conversion and over 99% selectivity to FOL at 25 °C under 1 MPa of hydrogen in water. The kinetic behaviour of the selective hydrogenation of FAL to FOL with the 3 wt% Pt/SiC-C-200-H2 catalyst was also investigated and the turnover frequency (TOF) reached 1148 h-1. Moreover, the Pt/SiC-C catalyst is more active than other Pt catalysts supported on ordered mesoporous carbon CMK-3, activated carbon, periodic mesoporous silica SBA-15 or Al2O3. Detailed characterization using XRD, N2-sorption, SEM, TEM and XPS techniques reveals that the striking performance of the Pt/SiC-C catalyst can be attributed to the optimal metal-support interaction and the interfacial effect.


Glufosinate-ammonium: a review of the current state of knowledge.
Glufosinate is a key herbicide to manage glyphosate-resistant weeds mainly because it is a broad-spectrum herbicide, and transgenic glufosinate-resistant crops are available. Although glufosinate use has increased exponentially over the past decade, the treated area with this herbicide is far less than that with glyphosate. This is because glufosinate often provides inconsistent performance in the field, which is attributed to several factors including environmental conditions, application technology, and weed species. Glufosinate is also highly hydrophilic and does not translocate well in plants, generally providing poor control of grasses and perennial species. In the soil, glufosinate is rapidly degraded by microorganisms, leaving no residual activity. While there have been concerns regarding glufosinate toxicology, its proper use can be considered safe. Glufosinate is a fast-acting herbicide that was first discovered as a natural product, and is the only herbicide presently targeting glutamine synthetase. The mode of action of glufosinate has been controversial, and the causes for the rapid phytotoxicity have often been attributed to ammonia accumulation. Recent studies indicate that the contact activity of glufosinate results from the accumulation of reactive oxygen species and subsequent lipid peroxidation. Glufosinate disrupts both photorespiration and the light reactions of photosynthesis, leading to photoreduction of molecular oxygen, which generates reactive oxygen species. The new understanding of the mode of action provided new ideas to improve the herbicidal activity of glufosinate. Finally, a very few weed species have evolved glufosinate resistance in the field, and the resistance mechanisms are generally not well understood requiring further investigation. © 2020 Society of Chemical Industry.


Mutagenicity testing of organic extracts of diesel exhaust particles after spiking with polycyclic aromatic hydrocarbons (PAH).
In the present study, spiking was used as a strategy to evaluate the mutagenicity of individual compounds in a mixture. Mutagenicity of individual polycyclic aromatic hydrocarbons (PAH) was evaluated in an organic extract of diesel exhaust particles (DEP). The particles were extracted with dichloromethane (DCM). After replacing DCM with dimethylsulphoxide (DMSO), the extract was spiked with four individual PAH: benzo(a)pyrene, benzo(a)anthracene, pyrene and fluoroanthene. The PAH were added separately and in various combinations to the extract to determine the effects of each variable and to identify possible interactions between the individual PAH and between the PAH and the extract. The study was designed as a fractional factorial experiment with the five variables (the DEP extract and the four PAH), giving 16 (instead of 32) mixtures plus a triplicate centrepoint and background, i.e. a total of 20. The fractionated factorial design used in the present work supports a model with linear and interaction terms. The mixtures were tested for mutagenicity in the Ames assay using four strains of Salmonella typhimurium in the presence of rat liver xenobiotic enzymes (S9-mix). Projections to Latent Structures (PLS) was used to quantify the mutagenicity of each compound and possible interactions. The four individual PAH and the DEP extract acted additively in the Ames test with 10% S9-mix.


Aided Electrophysiology Using Direct Audio Input: Effects of Amplification and Absolute Signal Level.
This study investigated (a) the effect of amplification on cortical auditory evoked potentials (CAEPs) at different signal levels when signal-to-noise ratios (SNRs) were equated between unaided and aided conditions, and (b) the effect of absolute signal level on aided CAEPs when SNR was held constant. CAEPs were recorded from 13 young adults with normal hearing. A 1000-Hz pure tone was presented in unaided and aided conditions with a linear analog hearing aid. Direct audio input was used, allowing recorded hearing aid noise floor to be added to unaided conditions to equate SNRs between conditions. An additional stimulus was created through scaling the noise floor to study the effect of signal level. Amplification resulted in delayed N1 and P2 peak latencies relative to the unaided condition. An effect of absolute signal level (when SNR was constant) was present for aided CAEP area measures, such that larger area measures were found at higher levels. Results of this study further demonstrate that factors in addition to SNR must also be considered before CAEPs can be used to clinically to measure aided thresholds.