Search

Purpose: Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34–43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene's solubility as the responsible mechanism. Methods: The effects of green tea extract, (–)-epigallocatechin gallate (EGCG), and (–)-epigallocatechin (EGC) on raloxifene's solubility were assessed in fasted state simulated intestinal fluids (FaSSIF) and fed state simulated intestinal fluids (FeSSIF). EGCG and EGC represent green tea's main bioactive constituents, flavan-3-gallate and flavan-3-ol catechins respectively, and the tested concentrations (mM) match the µg/mg of each compound in the extract. Our mouse study (n = 5/time point) evaluated the effect of green tea extract and EGCG on the systemic exposure of raloxifene. Results: EGCG (1 mM) and EGC (1.27 mM) decreased raloxifene's solubility in FaSSIF by 78% and 13%, respectively. Micelle size in FaSSIF increased with increasing EGCG concentrations (> 1000% at 1 mM), whereas EGC (1.27 mM) did not change micelle size. We observed 3.4-fold higher raloxifene solubility in FeSSIF compared to FaSSIF, and neither green tea extract nor EGCG significantly affected raloxifene solubility or micelle size in FeSSIF. The mice study showed that green tea extract significantly decreased raloxifene Cmax by 44%, whereas EGCG had no effect. Green tea extract and EGCG did not affect the AUC0-24 h of raloxifene or the metabolite-to-parent AUC ratio. Conclusions: This study demonstrated flavan-3-gallate catechins may decrease solubility of poorly water-soluble drugs such as raloxifene, particularly in the fasted state. [ABSTRACT FROM AUTHOR]

Bispecific antibodies have recently received approval for relapsed refractory B-cell lymphomas (r/r BCL). Little is known about the safety of radiation (RT) delivered with bispecific therapy (BT). We sought to assess the toxicity of combination therapy with BT and RT. We retrospectively identified patients (pts) at a single institution receiving BT and RT between 2018 and 2023. The temporal relationship of RT with respect to BT was defined as follows: "Pre-BT" RT 3 months (mo) prior to and up to the first dose of BT, "Peri-BT" 1 or more RT fractions between the first and last bispecific dose, "Post-BT" RT after the last BT dose through 3 mo post-BT. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT, and all other toxicities per CTCAE version 5. Nineteen patients underwent 20 courses of BT and received RT to 34 lesions. BT included mosunetuzumab (8), blinatumomab (7), epcoritamab (4), and glofitamab (1), with median BT treatment duration of one mo (0-6). Median follow up post RT and post BT was 2 mo (0-48) and 1 mo (0-48), respectively. Baseline characteristics were as follows: median age 61 (45-86), 25% female, 55% ECOG 0-1, histology DLBCL 65%, FL 25%, Grey zone 5%, Burkitt 5%, prior treatments 4.5 (1-12), 45% prior CAR T, 85% advanced stage, 80% extranodal, and 15% bulky disease (> 10 cm). Of the radiated lesions, 56% were Pre-BT (38% within 4 weeks of BT start), 21% Peri-BT, and 26% Post-BT. Sites treated included 29% spine/paraspinal, 21% abdomen/pelvis, 18% axilla, 15% head/neck, 6% skin/subcutaneous, 6% thorax, 6% CNS. Eighty-eight percent of lesions received RT with palliative intent. 16% of pts received comprehensive RT to all active lesions (5% bridging pre-BT, 11% salvage). Median CTV was 174 cc (10-4376). Median total dose was 20 Gy (4-45). Among DLBCL pts, the most common regimens included 20 Gy/5 fx (64%), 8 Gy/2 fx (16%), and 30 Gy/10 fx (12%). Common regimens among FL pts included 4 Gy/2 fx (50%), 8 Gy/2 fx (17%), and 30 Gy/10 fx (17%). CRS and ICANS events were infrequent, and all low grade (4 (20%) Gr 1-2; 3 (15%) Gr 1-2, respectively). Radiation-related toxicities were similarly all low grade. Of all lesions treated, 35% were associated with Gr 1 toxicities, and 24% with Gr 2. Toxicities included fatigue (29%), dermatitis (21%), nausea (9%), GI (15%), pain (3%) and dry mouth (3%). No patients were hospitalized for bispecific related toxicity. RT with BT appears safe, with acceptable rates of low grade, RT-related toxicity. CRS and ICANS events were infrequent and all low grade, suggesting no obvious exacerbation by RT. The safety and efficacy of combination RT and BT warrants further study in larger cohorts. [ABSTRACT FROM AUTHOR]

As a genomic resource provider, grappling with getting a handle on how your resource is utilized can be extremely challenging. At the same time, being able to thus document the plethora of use cases is vital to demonstrate sustainability. Herein, we describe a flexible workflow, built on readily available software, that the Human Disease Ontology (DO) project has utilized to transition to semi-automated methods to identify uses of the ontology in the published literature. The novel R package DO.utils (https://github.com/DiseaseOntology/DO.utils) has been devised with a small set of key functions to support our usage workflow in combination with Google Sheets. Use of this workflow has resulted in a 3-fold increase in the number of identified publications that use the DO and has provided novel usage insights that offer new research directions and reveal a clearer picture of the DO's use and scientific impact. The DO's resource use assessment workflow and the supporting software are designed to be useful to other resources, including databases, software tools, method providers and other web resources, to achieve similar results. Database URL: https://github.com/DiseaseOntology/DO.utils [ABSTRACT FROM AUTHOR]

Objectives: We discuss two patients with antiphospholipid syndrome (APS) who presented with critical ischemia of both lower extremities due to arterial microthrombi. They received multimodality therapy emergently: anticoagulation, immunosuppression, and therapeutic plasma exchange (TPE). Then they were maintained on anticoagulation with fondaparinux and immunosuppression with mycophenolate mofetil (MMF), and were followed for 4 years. Methods: Two patients with APS with ischemia and necrosis of their distal lower extremities were treated emergently with anticoagulation (intravenous heparin), immunosuppression (prednisone), and TPE. They were maintained on anticoagulation with fondaparinux and immunosuppression with MMF. Results: Neither patient had recurrent microthrombotic disease during a 4-year follow-up. Conclusions: As described in our small cohort, patients with APS who suffer from microthrombotic arterial disease may benefit from maintenance therapy of anticoagulation with fondaparinux and immunosuppression with MMF, an approach which may be worthy of further trial. Fondaparinux does not require attention to diet, monitoring, and cumbersome bridging that is typical of warfarin therapy. MMF provides immunosuppression while sparing the side effects of steroid treatment. [ABSTRACT FROM AUTHOR]

Objective: Intra-abdominal adhesions are associated with an increased risk of complications during repeat Cesarean section (CS), such as bladder and bowel injury, hemorrhage, infection and hysterectomy. We present a simple sonographic marker, the 'sliding sign' of the uterus, for the prediction of intra-abdominal adhesions in the third trimester of pregnancy in women undergoing repeat CS.Methods: This was a prospective observational study of pregnant women with a history of at least one Cesarean delivery evaluated by transabdominal ultrasound during the third trimester of an ongoing pregnancy. In order to diagnose intra-abdominal adhesions, we assessed a sonographic sign, the sliding of the uterus under the inner part of the fascia of the abdominal muscles during deep breathing. Women were considered to be at high risk for severe adhesions if uterine sliding was absent and at low risk in the presence of obvious or moderate uterine sliding. A comparison between sonographic findings and intra-abdominal adhesions observed during surgery was performed.Results: Of the 63 patients with one or more previous CS examined, 59 completed the study and underwent CS at our institution. In 16 of the 19 cases assigned to the high-risk group for severe adhesions due to absence of sliding of the uterus, the suspicion was confirmed at surgery. The prediction of low risk for adhesions was confirmed in 35 out of 40 patients. The sensitivity and specificity of the sliding sign in predicting presence of intra-abdominal adhesions in women undergoing repeat CS were 76.2% and 92.1%, respectively. Inter- and intraobserver correlation using Cohen's kappa coefficient were 0.52 and 0.77, respectively.Conclusion: Our data show that a simple sonographic sign might be able to discriminate between high and low risk for intra-abdominal adhesions in patients with a history of Cesarean delivery. This technique may aid clinical decisions in patients undergoing repeat CS. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Summary: Background: Minimal hepatic encephalopathy (HE) and HE grade 1 (HE1) according to the West Haven criteria have recently been grouped as one entity named—covert HE‐ (CHE). Data regarding the impact of CHE on health‐related quality of life (HRQoL) and sleep quality are controversial. Aim: First, to determine whether CHE affects HRQoL and sleep quality of cirrhotic patients and second, whether minimal HE (MHE) and HE1 affect HRQoL and sleep quality to a comparable extent. Methods: A total of 145 consecutive cirrhotic patients were enrolled. HE1 was diagnosed clinically according to the West Haven criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to detect MHE. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL and Pittsburgh Sleep Quality Index (PSQI) was applied to assess sleep quality. Results: Covert HE was detected in 59 (40.7%) patients (MHE: n = 40; HE1: n = 19). Multivariate analysis identified CHE (P < 0.001) and female gender (P = 0.006) as independent predictors of reduced HRQoL (CLDQ total score). CHE (P = 0.021), low haemoglobin (P = 0.024) and female gender (P = 0.003) were identified as independent predictors of poor sleep quality (PSQI total score). Results of CLDQ and PSQI were comparable in patients with HE1 and MHE (CLDQ: 4.6 ± 0.9 vs 4.5 ± 1.2, P = 0.907; PSQI: 11.3 ± 3.8 vs 9.9 ± 5.0, P = 0.3). Conclusion: Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice. [ABSTRACT FROM AUTHOR]

Doxycycline and, to a lesser extent, minocycline, have been used for decades to treat various serious systemic infections, but many physicians remain unfamiliar with their spectrum, interpretation of susceptibility results, pharmacokinetic/pharmacodynamic (PK/PD) properties, optimal dosing regimens, and their activity against MRSA, VRE, and multidrug-resistant (MDR) Gram-negative bacilli, e.g., Acinetobacter sp. This article reviews the optimal use of doxycycline and minocycline to treat a variety of infections and when minocycline is preferred instead of doxycycline. [ABSTRACT FROM AUTHOR]

Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high-fat (HF) diet for 2 hours a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2-hour scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs 24 hours ad libitum feeding on the same HF diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine-and amphetamine-regulated transcript, pro-opiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), as well as enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain, were measured by in situ hybridisation. Mice fed ad libitum on a HF diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, although they did not appear to be related to feeding behaviour in the schedule-fed groups (ie, the large, binge-type meals) and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by nonhomeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, although it still leaves open the fundamental question about the underlying mechanisms of meal feeding. [ABSTRACT FROM AUTHOR]

Objective: This study builds on the limited research documenting Cystic Fibrosis (CF) patients' understanding of treatment recommendations and how this may impact adherence to therapy.Methods: We surveyed adults with CF and their healthcare professional (HCP) to capture treatment recommendations provided by the HCP, and patients' knowledge, and frequency of performance, of these recommendations. We classified CF participants' understanding of treatment recommendations (correct/incorrect) as compared to the actual recommendations made by the HCP. We computed CF participants' adherence in relation to HCP treatment recommendations and to their own understanding of treatment recommendations (adherent/non-adherent).Results: Complete HCP and patient data were available for 42 participants. The recommended treatment frequency was correctly understood by 0%-87.8% of CF participants. Adherence to HCP treatment recommendations ranged from 0 to 68.3% (mean 45.4%±21.5), and rates were low (<33%) for acapella, percussion/postural drainage, tobramycin nebulization and insulin. Participants' adherence was greater when calculated in relation to participants' understanding of treatment recommendations (62.4%±25.1) than when calculated in relation to actual HCP treatment recommendations (45.4%±21.5%) (p=0.009).Conclusion and Practice Implications: Adults with CF misunderstand treatment recommendations; this likely affects treatment adherence. Interventions to ensure HCPs use effective communication strategies are needed. [ABSTRACT FROM AUTHOR]

The article presents a case study of three white patients with Brooke–Spiegler syndrome (BSS) who were initially diagnosed both clinically and histopathologically. Topics include mutation analysis of the cylindromatosis (CYLD) gene, which revealed three splice site mutations and assessment of the expression of CYLD in normal human epidermal keratinocytes (NHEK), leucocytes and peripheral blood mononuclear cells (PBMC) by quantitative reverse transcriptase (qRT)-PCR.

This study investigated the impact of water pretreatments (i.e. activated carbon, ferric chloride and polyelectrolyte organic polymer) and dynamic chemical ageing by chlorine on performances of PES/PVP hollow fiber membranes. For this, several filtration experiments were carried out on pristine membranes and on 5-year-old membranes sampled from a large drinking water treatment plant (DWTP membranes) exhibiting strong fouling event with no clear explanation. Autopsy performed on the DWTP membranes revealed the presence of a brown fouling layer consisting of organic matters, iron, flocculent polymer and activated carbon. Filtration tests showed the strong fouling sensitivity of the autopsied membranes compared to the pristine membranes. Further autopsy analyses and filtration experiments demonstrated the link between PVP degradation inside the membrane due to frequent chlorine backwashes and the increase in membrane fouling sensitivity. [ABSTRACT FROM AUTHOR]

Metal ornaments from Únětice ( Mierczyce, Tomice, Jordanów and Opatowice) and Urnfield culture ( Szprotawa, Żarek and Wrocław Żerniki) sites in south-west Poland are made of bronze of varying composition, with the exception of the early Bronze Age Przecławice site, where the copper items are found in graves from stages III/ IV. The combined XRF and electron microprobe study of 37 ornaments (mostly pins) shows that those excavated from Únětice culture graves usually consist of cored dendrites, plus a Sb-rich phase in some. The copper objects from Przecławice correspond in composition to the East Alpine Copper or to the Ösenring copper and were produced from fahlore. Those from the Urnfield culture sites consist of homogeneous bronze. The Únětice culture ornaments were produced with little control of the effect of varying bronze composition on its microstructure. The results of XRF analyses of heterogeneous metal artefacts vary depending on the proportion of phases in the analysed site, and should be combined with micrometre-scale analytical data and microstructural information yielded by electron microprobe methods. The same refers to deeply weathered or corroded objects made of homogeneous metal, which contain irregularly dispersed decomposition products. [ABSTRACT FROM AUTHOR]

In eukaryotes, the Cu/Zn containing superoxide dismutase (SOD1) plays a critical role in oxidative stress protection as well as in signaling. We recently demonstrated a function for Saccharomyces cerevisiae Sod1p in signaling through CK1γ casein kinases and identified the essential proton ATPase Pma1p as one likely target. The connection between Sod1p and Pma1p was explored further by testing the impact of sod1Δ mutations on cells expressing mutant alleles of Pma1p that alter activity and/or post-translational regulation of this ATPase. We report here that sod1Δ mutations are lethal when combined with the T912D allele of Pma1p in the C-terminal regulatory domain. This “synthetic lethality” was reversed by intragenic suppressor mutations in Pma1p, including an A906G substitution that lies within the C-terminal regulatory domain and hyper-activates Pma1p. Surprisingly the effect of sod1Δ mutations on Pma1-T912D is not mediated through the Sod1p signaling pathway involving the CK1γ casein kinases. Rather, Sod1p sustains life of cells expressing Pma1-T912D through oxidative stress protection. The synthetic lethality of sod1Δ Pma1-T912D cells is suppressed by growing cells under low oxygen conditions or by treatments with manganese-based antioxidants. We now propose a model in which Sod1p maximizes Pma1p activity in two ways: one involving signaling through CK1γ casein kinases and an independent role for Sod1p in oxidative stress protection. [ABSTRACT FROM AUTHOR]

The effect of a cord entanglement on perinatal outcomes, such as fetal demise, Caesarean section rate and low Apgar score is controversial. The aim of this study was to evaluate the impact of cord entanglement on perinatal outcomes. Umbilical cord entanglement around various fetal body parts is usually an incidental diagnosis during delivery. [Extracted from the article]

We have developed an immunochromatographic test for the diagnosis of peste des petits ruminants ( PPR) under field conditions. The diagnostic assay has been tested in the laboratory and also under field conditions in Ivory Coast, Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The specificity was 95% over all nasal and ocular samples. The test detected as little as 103 TCID50 (50% tissue culture infectious doses) of cell culture-grown virus, and detected virus isolates representing all four known genetic lineages of peste des petits ruminants virus. Virus could be detected in swabs from animals as early as 4 days post-infection, at a time when clinical signs were minimal. Feedback from field trials was uniformly positive, suggesting that this diagnostic tool may be useful for current efforts to control the spread of PPR. [ABSTRACT FROM AUTHOR]

Complementary electrochemical and spectroscopic techniques were used to characterize the behavior and composition of the passive layer formed at the gold surface in a thiosulfate electrolyte in the presence of cupric ions. Raman studies of three different cationic (calcium, ammonium, and sodium) thiosulfate leaching solutions revealed that the concentrations of thiosulfate, trithionate, sulfate, and tetrathionate remained constant in the bulk solution over a 3-h time period. The initial leaching current densities of these three systems were identical; however, significant differences in the open circuit potentials of these systems were observed. To provide additional information about the nature of the passive layer, gold nanorod array electrodes were fabricated and employed as substrates for studying the species present at the gold-thiosulfate interface using surface-enhanced Raman spectroscopy (SERS). The composition and behavior of the passive layer at the gold-thiosulfate interface greatly differed from those of the bulk solutions. The passive layer consisted primarily of elemental sulfur and sulfide-like species, with thiosulfate and its oxidation products, such as tri- and tetrathionates, as minority components. The nature of the cation (calcium, sodium, or ammonium) of the thiosulfate salt showed no significant effect on the composition of the passive layer at leaching times longer than 100 min. In addition, the presence of cupric ions also had no significant effect on the formation of the passive layer. However, copper is a much better oxidant than oxygen in gold-thiosulfate leaching reactions. [ABSTRACT FROM AUTHOR]

The Standard Model of particle physics is known to be incomplete. Extensions to the Standard Model, such as weak-scale supersymmetry, posit the existence of new particles and interactions that are asymmetric under time reversal (T) and nearly always predict a small yet potentially measurable electron electric dipole moment (EDM), de, in the range of 10-27 to 10-30 e·cm. The EDM is an asymmetric charge distribution along the electron spin (S) that is also asymmetric under T. Using the polar molecule thorium monoxide, we measured de = (-2.1 ± 3.7stat ± 2.5syst) × 10-29 e·cm. This corresponds to an upper limit of |de| < 8.7 × 10-29 e·cm with 90%confidence, an order of magnitude improvement in sensitivity relative to the previous best limit. Our result constrains T-violating physics at the TeV energy scale. [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

Nearly all freshwaters and coastal zones of the US are degraded from inputs of excess reactive nitrogen (Nr), sources of which are runoff, atmospheric N deposition, and imported food and feed. Some major adverse effects include harmful algal blooms, hypoxia of fresh and coastal waters, ocean acidification, long-term harm to human health, and increased emissions of greenhouse gases. Nitrogen fluxes to coastal areas and emissions of nitrous oxide from waters have increased in response to N inputs. Denitrification and sedimentation of organic N to sediments are important processes that divert N from downstream transport. Aquatic ecosystems are particularly important denitrification hotspots. Carbon storage in sediments is enhanced by Nr, but whether carbon is permanently buried is unknown. The effect of climate change on N transport and processing in fresh and coastal waters will be felt most strongly through changes to the hydrologic cycle, whereas N loading is mostly climate-independent. Alterations in precipitation amount and dynamics will alter runoff, thereby influencing both rates of Nr inputs to aquatic ecosystems and groundwater and the water residence times that affect Nr removal within aquatic systems. Both infrastructure and climate change alter the landscape connectivity and hydrologic residence time that are essential to denitrification. While Nr inputs to and removal rates from aquatic systems are influenced by climate and management, reduction of N inputs from their source will be the most effective means to prevent or to minimize environmental and economic impacts of excess Nr to the nation's water resources. [ABSTRACT FROM AUTHOR]

Although yeast cells grown in abundant glucose tend to acidify their extracellular environment, they raise thepHof the environment when starved for glucose or when grown strictly with non-fermentable carbon sources. Following prolonged periods in this alkaline phase, Saccharomyces cerevisiae cells will switch to producing acid. The mechanisms and rationale for this "acid burst" were unknown. Herein we provide strong evidence for the role of mitochondrial superoxide in initiating the acid burst. Yeast mutants lacking the mitochondrial matrix superoxide dismutase (SOD2) enzyme, but not the cytosolic Cu,Zn-SOD1 enzyme, exhibited marked acceleration in production of acid on non-fermentable carbon sources. Acid production is also dramatically enhanced by the superoxide-producing agent, paraquat. Conversely, the acid burst is eliminated by boosting cellular levels of Mn-antioxidant mimics of SOD. We demonstrate that the acid burst is dependent on the mitochondrial aldehyde dehydrogenase Ald4p. Our data are consistent with a model in which mitochondrial superoxide damage to Fe-S enzymes in the tricarboxylic acid (TCA) cycle leads to acetate buildup by Ald4p. The resultant expulsion of acetate into the extracellular environment can provide a new carbon source to glucose-starved cells and enhance growth of yeast. By triggering production of organic acids, mitochondrial superoxide has the potential to promote cell population growth under nutrient depravation stress. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 901–907 Background The risk of dying from gastric cancer appears to have increased among consecutive generations born during the 19th century. Aim To follow the time trends of hospitalization for gastric cancer and test whether they confirm such increase. Methods Inpatient records of the last two centuries from four hospitals in Scotland and three US hospitals were analysed. Proportional rates of hospitalization for gastric cancer, gastric ulcer and duodenal ulcer were calculated during consecutive 5-year periods. Results The data from all seven cities revealed strikingly similar patterns. No hospital admissions for gastric cancer or peptic ulcer were recorded prior to 1800. Hospital admissions for gastric cancer increased in an exponential fashion throughout the 19th and the beginning of the 20th century. In a majority of cities, the rise in hospitalization for gastric cancer preceded a similar rise in hospitalization for gastric ulcer. Hospitalization for these two latter diagnoses clearly preceded hospitalization for duodenal ulcer by 20–40 years. Conclusions The occurrence of gastric cancer, gastric ulcer and duodenal ulcer markedly increased during the 19th century. Improvements in hygiene may have resulted in the decline of infections by other gastrointestinal organisms that had previously kept concomitant infection by Helicobacter pylori suppressed. [ABSTRACT FROM AUTHOR]

Abstract: The combustion of hydrogen in a hot, bubbling bed of quartz sand fluidized by air has been studied for the first time, by injecting hydrogen just above the distributor, via six horizontal fine tubes of Cr/Ni. Overall the fluidizing gas was oxygen-rich, with the composition varying from nearly stoichiometric to very lean mixtures. With the bed initially fluidized at room temperature, combustion (after ignition by a pilot flame) occurs in a premixed flame sitting on top of the bed. When the sand warms up, combustion becomes explosive in bubbles leaving the bed, exactly as with a hydrocarbon as fuel. However, in contrast to hydrocarbons, it is clear that when the bed reaches 500–600 °C, heat is produced both above the top of the bed (because of H2 bypassing the bed) and very low down in the bed. In fact, with hydrogen as fuel, the location of where bubbles ignite descends abruptly to low in the sand; furthermore, the descent occurs at ∼500 °C, which is ∼100 K below the ignition temperature predicted by well-established kinetic models. However, the kinetic models do reproduce the observations, if it is assumed that the Cr/Ni hypodermic tubes, through which the fuel was injected, exert a catalytic effect, producing free H atoms, which then give rise to HO2 radicals. In this situation, kinetic modeling indicates that bubbles ignite when they become sufficiently large and few enough to have a lifetime (i.e. the interval between their collisions) longer than the ignition delay for the temperature of the sand. The amounts of NO found in the off-gases were at a maximum (24 ppm), when the bed was at ∼500 °C for . The variations of [NO] with [air]/[H2] and also temperature indicate that NO is produced, at least partly, via the intermediate N2H. In addition, the air-afterglow emission of green light (from ) was observed in the freeboard, indicating the presence there of both NO and free atoms of oxygen for . [Copyright &y& Elsevier]

Background: Component-resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray-based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. Methods: We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. Results: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component-resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. Conclusions: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double-blind, placebo-controlled food challenges in most cases. [ABSTRACT FROM AUTHOR]

Preventing death and limiting handicap from ischaemic stroke are major goals that can be achieved only if the pathophysiology of infarct expansion is properly understood. Primate studies showed that following occlusion of the middle cerebral artery (MCA)––the most frequent and prototypical stroke, local tissue fate depends on the severity of hypoperfusion and duration of occlusion, with a fraction of the MCA territory being initially in a ‘penumbral’ state. Physiological quantitative PET imaging has translated this knowledge in man and revealed the presence of considerable pathophysiological heterogeneity from patient to patient, largely unpredictable from elapsed time since onset or clinical deficit. While these observations underpinned key trials of thrombolysis, they also indicate that only patients who are likely to benefit should be exposed to its risks. Accordingly, imaging-based diagnosis is rapidly becoming an essential component of stroke assessment, replacing the clock by individually customized management. Diffusion- and perfusion-weighted MR (DWI-PWI) and CT-based perfusion imaging are increasingly being used to implement this, and are undergoing formal validation against PET. Beyond thrombolysis per se, knowledge of the individual pathophysiology also guides management of variables like blood pressure, blood glucose and oxygen saturation, which can otherwise precipitate the penumbra into the core, and the oligaemic tissue into the penumbra. We propose that future therapeutic trials use physiological imaging to select the patient category that best matches the drug's presumed mode of action, rather than lumping together patients with entirely different pathophysiological patterns in so-called ‘large trials’, which have all failed so far.British Journal of Pharmacology (2008) 153, S44–S54; doi:10.1038/sj.bjp.0707530; published online 26 November 2007 [ABSTRACT FROM AUTHOR]

The Food Quality Protection Act (FQPA) was enacted in August 1996 and required the US Environmental Protection Agency (EPA) to reassess all existing and new crop protection active substances using a new set of health and environmental standards to further protect infants and children. The initial fear that many minor or specialty crop use registrations would be lost without adequate replacements has largely been overcome by an aggressive programme by the International Research Project no. 4 (IR-4) in partnership with the EPA and the crop protection industry to register new, safer, reduced risk products for specialty crop pest control needs. Since the FQPA, the EPA has approved over 5600 new specialty crop uses resulting from IR-4 residue programmes. This amounts to about 56% of the over 10 000 clearances received by the IR-4 programme in its 43 year history and about 50% of all new uses granted by the EPA since FQPA. The positive outcomes from these efforts have been partially negated by the lack of tolerances or Maximum Residue Levels (MRLs) in countries to which US produce is exported. This has forced some US specialty crop growers to continue to use older, less desirable products. IR-4 has been addressing this challenge by cooperating in the NAFTA (North American Free Trade Agreement) countries with Agriculture and Agri-Food Canada's Pest Management Centre and Health Canada's Pest Management Regulatory Agency to harmonize MRLs through joint projects and regulatory reviews. IR-4 has also provided leadership for the International Crop Grouping Consulting Committee to harmonize specialty/minor crop groupings and representative crops for residue studies with the long-term goal being to globally harmonize MRLs. [ABSTRACT FROM AUTHOR]

Abstract: Wastes burned in incinerators usually contain polymers, whose combustion can be associated with noxious emissions, unless the conditions are properly selected. This paper investigates how polymers burn in a fluidised bed; in fact, the combustion of a number of polymers, including several types of polyethylene, polystyrene and a polyamide, was studied in a laboratory-size, bubbling, fluidised bed, filled with quartz sand, with no external heating. Pellets of a polymer were mostly thrown into such a bed of sand, fluidised and maintained hot by a fuel-lean mixture of propane, methane or hydrogen in air, which burned soon after entering the bed. In addition, polymers were also used as the only fuel, i.e., added to a hot bed fluidised by only air. Visual observations of burning polymer pellets up to ∼240mg were made, as well as video records obtained and the flue gas composition monitored, when the combustor was run at 800–1000°C with 1.1–2.0 times more O2 than required for complete combustion. It is clear that a polymer burns as if its volatile content were 100%. The polymer pellet first melts at a rate controlled by heat transfer. However, the melt and the gaseous products of thermal decomposition are dispersed, albeit sometimes slowly, in a fluidised bed. Although the high U/U mf of above 10 caused some back-mixing of the gas leaving the bed and the combustion efficiency was high (assessed from O2 consumption and CO2 production), long streaks or plumes of fuel-rich gases (from each polymer pellet) did reach the freeboard, i.e., these plumes burned as transient diffusion flames at a rate controlled by mixing. By increasing the temperature and the residence times of gas in the bed and freeboard, the observed emissions of CO and hydrocarbons could be considerably reduced. The concentrations of NO were low, except when the polymer contained chemically-combined nitrogen, as in a polyamide. It is concluded that bubbling fluidised beds can be good for incinerating polymers, possibly together with other wastes. [Copyright &y& Elsevier]

Background Stomach pain and discomfort have been reported since antiquity. Aim To follow the time trends since the 18th century of dyspepsia, gastric ulcer, duodenal ulcer, and benign oesophageal disease to test when dyspepsia started to become a major clinical problem. Methods The annual in- and out-patient records of the last three centuries from the Scottish Royal Infirmaries of Edinburgh, Aberdeen, Glasgow and Dundee were analysed. In addition, dispensary attendances, clinicians' casebooks, students' notebooks and medical texts have been scrutinized for historic statistics of upper gastrointestinal disease. Results Dyspepsia was first recorded in the 1750s and increased markedly subsequently. Such dyspepsia persisted after gastric and duodenal ulcers appeared in the late 19th century and then declined again in the late 20th century. Non-ulcer dyspepsia has remained the commonest diagnosis made after endoscopy for stomach pain in the beginning of the 21st century. Conclusion The current commonest diagnosis of stomach pain, dyspepsia dates from the mid-18th century. Any explanations of its causation need to consider this timing. [ABSTRACT FROM AUTHOR]

We presented a Web questionnaire to 139 physicians and medical researchers and 109 laypeople. The subjects made judgments of badness and importance of prevention for eight medical conditions at each of seven different probability levels. By assuming that the response to each of the 56 risks was monotonically related to transformations of the probability and of the disutility of the condition, we could assess the relative effect of probability and disutility on each subject's judgments. Physicians' judgments were more sensitive than laypeople's judgments to changes in probability. Older and female laypeople were less sensitive to probability (and correspondingly, more responsive to differences in severity among medical conditions). Laypeople varied more than physicians in their responsiveness to probability. These results point to general individual differences in the effect of probability on evaluations of medical risks. They may also provide insight into causes and noncauses of physician-patient miscommunication. [ABSTRACT FROM AUTHOR]

Because it is the main determinant of clinical recovery, early reperfusion of the ischemic penumbra has become the mainstay of acute stroke therapy. Although early permanent recanalization can be associated with spectacular and complete recovery, some patients in fact exhibit delayed or incomplete recovery, even despite small infarcts on late structural imaging. This might result from tissue inflammation and selective neuronal death/damage, two probably inter-related cellular events well described in the animal literature, precluding full functional restoration in the salvaged penumbra. However, impact of these processes on recovery may be complex because of the interplay with ongoing plasticity and the possible promoting effect of inflammation on the latter. Preliminary results from imaging studies of inflammation and selective neuronal loss after middle cerebral artery territory stroke, using radioligands of the central benzodiazepine receptor and the activated microglia, respectively, reviewed here, suggest these phenomena also exist in man, although their relationship with acute-stage hypoperfusion and their impact on clinical recovery, if any, remain poorly understood. Furthermore, their inter-relationships in the salvaged penumbra have not been addressed. Better understanding of these potentially harmful processes might help to maximize benefits from thrombolysis, and could also have implications for patients who enjoy spontaneous recanalization. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Knowledge of the different surgical approaches of the ureter remains necessary for the urologist as many ureteral diseases cannot be treated by simple urological access (endo-urology). Open and laparoscopic accesses of the 4 parts of the ureter (lombar, iliac, pelvic and terminal parts) are described. [Copyright &y& Elsevier]

Summary Background : Although dyspepsia has been described for thousands of years, few studies have analysed its incidence before the 19th century when peptic ulcer first became a major dyspepsia-producing disease. Methods : The incidence of alimentary disease around 1800 was examined in three private practices for the fee-paying middle class and in five public dispensaries for the poor in London, as well as in one dispensary in New York. Results : The proportions of attendances for alimentary disorders were identical, 16%, in each of the three groups. Diarrhoea and dysentery were twice as common in the London dispensary than in private practice, presumably because of poor sanitation. Dyspepsia showed a similar incidence in the London dispensary and private practice, but was only half as common in New York. Worms were three times more common in dispensary patients in New York than in London. The incidence of diarrhoea and dyspepsia indicated no significant time trends over 43 years. None of the alimentary causes of death showed peptic ulcer at necropsy, and both haematemesis and intestinal haemorrhage were rare. Conclusions : Around 1800, the infrequent deaths from alimentary conditions suggested that the ulcer epidemic had not yet started. Instead, it is probable that the dyspepsia was similar to the non-ulcer dyspepsia of today. [ABSTRACT FROM AUTHOR]

A laboratory size quartz reactor has been used to burn methane, LPG (liquid petroleum gas) and aromatic hydrocarbon vapors in a bubbling fluidized bed. Most measurements and observations were made for lean mixtures of fuel and air with quartz sand in the bed, but in some experiments NO, NO2, or CCl4 were introduced with the fuel, the stoichiometry was varied or the bed material changed. The quantities monitored were the bed temperature at two levels and the freeboard concentrations of O2, CO2, CO, NO, NO2, and in some runs, of hydrocarbons. An attempt was made to relate the measurements to the sound level and to visual observations. The results obtained suggest that with the air excess, λ, constant at 1.4 and with the bed at above ∼850 °C, the fuel can be fully oxidized and [CO] very low. [NO] is also low and does not increase even if the temperature is raised by another 150 to 200 °C. However, such a stable combustion process can be perturbed by adding a chemical inhibitor. With a suitable bed material it is possible to lower [CO] and [NO] in the freeboard to ∼1 ppm. At lower temperatures, with [CO] high, the conversion of NO to NO2 takes place. Most of the observations are consistent with the dominance of gas-phase reactions in the bubbles, but some effects can only be accounted for by the participation of heterogeneous chemical reactions. [Copyright &y& Elsevier]

Many systemic diseases impair linear growth. If remission occurs, growth will often accelerate beyond the normal rate for age, a phenomenon termed ”catch-up growth.” As a result, final height is improved, although this recovery of adult stature is frequently incomplete. Two principal models have been proposed to explain catch-up growth. The first model postulates a central nervous system mechanism that compares actual body size with an age-appropriate set-point and then adjusts growth rate accordingly. However, there is recent evidence that growth inhibition in a single growth plate is followed by local catch-up growth, a finding not readily explained by the neuroendocrine model. Thus, a new model has been proposed that places the mechanism within the growth plate itself. According to this model, growth-inhibiting conditions decrease proliferation of growth plate stem cells, thus conserving their proliferative potential. Additional research is needed to determine whether the mechanisms governing catch-up growth are local, systemic, or both. [ABSTRACT FROM AUTHOR]

Elevated LDH is associated with inferior outcomes for R/R BCL patients (pts) receiving chimeric antigen receptor T cells (CAR T). We assessed the proportion of pts who experience LDH normalization following bridging radiotherapy (BRT) and prognostic implications. We retrospectively analyzed 172 pts across 10 institutions who received BRT prior to CAR T from 2018-2020. LDH was collected both prior to leukapheresis (preBRT) and prior to CAR T infusion (postBRT) and classified as "Hi" or "Lo" based on institutional upper limits of normal. Pts were categorized into 4 groups: HiHi, HiLo, LoHi, and LoLo, based on their two respective LDH values. Progression-free survival (PFS) and overall survival (OS) were calculated from CAR T infusion using the Kaplan-Meier methods and modeled using Cox regression. Baseline characteristics were as follows: median age 62, 74% female, 71% diffuse large B cell lymphoma, 74% advanced stage, 39% bulky disease (≥10cm), 66% elevated preBRT LDH, 44% elevated postBRT LDH. 39% of pts received comprehensive BRT and 23% received systemic bridging. Of those with initially elevated LDH, 39% experienced normalization postBRT. Those with HiLo LDH had similar PFS and OS to those with LoLo LDH (p=0.42; p=0.64, respectively), and better PFS and OS compared to those with HiHi (p<0.001; p<0.001, respectively) and LoHi (p=0.002; p<0.001, respectively). Complete response (CR) rates differed between cohorts (p<0.001), with superior CR rates in HiLo and LoLo groups. Excluding pts who received systemic bridging, the PFS and OS differences across LDH subgroups were maintained (Table 1). Cytokine release syndrome grade 3+ events were low among all groups and neurotoxicity occurred less frequently among HiLo and LoLo cohorts (p=0.02). On multivariable analysis, pre-infusion normal LDH values (HR= 0.41, p<0.001) and comprehensive BRT (HR=0.42, p<0.001) maintained superior PFS. In pts with high preBRT LDH, those who achieved normalization were more likely to have received comprehensive BRT (p=0.002). Nearly 40% of pts with elevated pre-apheresis LDH experienced LDH normalization following BRT. These pts have superior clinical outcomes compared to those with persistently elevated LDH and comparable outcomes to those with persistently normal LDH. BRT may neutralize risk factors in at-risk pts with LDH response acting as a potential surrogate for treatment response. [ABSTRACT FROM AUTHOR]

• Recovery from MCLR toxicity did not resolve burnt-out NASH phenotype in NASH. • MCLR-elicited fibrosis persisted through 4 weeks of recovery in NASH. • MCLR persistently dysregulated cancer-related genes through 4 weeks of recovery in NASH. Nonalcoholic steatohepatitis (NASH) causes liver extracellular matrix (ECM) remodeling and is a risk factor for fibrosis and hepatocellular carcinoma (HCC). Microcystin-LR (MCLR) is a hepatotoxin produced by fresh-water cyanobacteria that causes a NASH-like phenotype, liver fibrosis, and is also a risk factor for HCC. The focus of the current study was to investigate and compare hepatic recovery after cessation of MCLR exposure in healthy versus NASH animals. Male Sprague-Dawley rats were fed either a control or a high fat/high cholesterol (HFHC) diet for eight weeks. Animals received either vehicle or 30 μg/kg MCLR (i.p: 2 weeks, alternate days). Animals were euthanized at one of three time points: at the completion of the MCLR exposure period and after 2 and 4 weeks of recovery. Histological staining suggested that after four weeks of recovery the MCLR-exposed HFHC group had less steatosis and more fibrosis compared to the vehicle-exposed HFHC group and MCLR-exposed control group. RNA-Seq analysis revealed dysregulation of ECM genes after MCLR exposure in both control and HFHC groups that persisted only in the HFHC groups during recovery. After 4 weeks of recovery, MCLR hepatotoxicity in pre-existing NASH persistently dysregulated genes related to cellular differentiation and HCC. These data demonstrate impaired hepatic recovery and persistent carcinogenic changes after MCLR toxicity in pre-existing NASH. [ABSTRACT FROM AUTHOR]

Presents evidence that cytochrome P450-dependent metabolism is involved in the formation of nominal antigen. Examples of specific immunological reactions to small molecular weight compounds on the level of T-lymphocytes; Presence of cytochrome P450 isoenzymes in antigen presenting cells.

Reports the results of a clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. Background; Methods; Results; Conclusions.

Reports on orientations and positions adopted by honeybees during search flights. Simplification of the storage and retrieval of retinotopic memories as the benefit of favored direction; Evidences of magnetic sense in bees.

La fasciite à éosinophiles est une maladie rare du tissu conjonctif caractérisée par un épaississement de la peau et des tissus mous. Elle peut survenir dans le cadre d'un SHE idiopathique ou secondaire. Les proliférations à éosinophiles secondaires aux immunothérapies anticancéreuses sont rares mais décrites. Parmi elles, les fasciites à éosinophiles sont peu rapportées. Nous en présentons ici un cas particulier compliqué d'une atteinte thoracique, secondaire à une immunothérapie anti-PD1. Une femme de 79 ans est traitée par Nivolumab pour un mélanome localement avancé. Elle développe une éosinophilie modérée à 8 mois de traitement, initialement à 0,7 G/L, progressant jusque 6,75 G/L à M11, sans autre cause retrouvée que son immunothérapie. Le Nivolumab est interrompu après 11 cures. L'éosinophilie régresse sous corticothérapie systémique per os, avant de réapparaître à l'arrêt de celle-ci (à M13 du début du Nivolumab soit à 2 mois de son arrêt). On remarque le développement d'œdèmes tendus et douloureux des mollets et des avant-bras avec « signe du canyon » responsables d'une limitation des amplitudes des poignets, évocateur de fasciite. S'y associe une dyspnée MRC2 sans étiologie cardiaque ou pulmonaire retrouvée. L'IRM musculaire retrouve un aspect de fasciite superficielle et profonde des mollets. L'échographie objective un épaississement diffus des fascias et de l'hypoderme au niveau des avant-bras et des membres inférieurs. Les EFR montrent un syndrome restrictif : CPT 59 % de la théorique, Tiffeneau normal. Le scanner thoracique et l'ETT sont normaux. Les relectures de TEP-scanners antérieurs objectivent l'apparition d'un hypermétabolisme modéré et d'un épaississement des fascias des membres inférieurs et supérieurs dès M11, associés à une hyperfixation au niveau des muscles intercostaux. Le diagnostic est confirmé à l'anatomopathologie, objectivant une fasciite avec présence d'un infiltrat mononucléé composé de polynucléaires éosinophiles, « nécrose » éosinophile du fascia. Malgré la reprise d'une corticothérapie systémique par boli puis PO, l'absence d'amélioration franche fera débuter un traitement de seconde ligne par Méthotrexate. Les inhibiteurs de checkpoint font partie de l'arsenal thérapeutique usuel en oncologie. À la différence de leurs effets secondaires les plus fréquents (colite, thyroïdite, hépatite), les complications cutanées et musculaires des anti-PD1 sont variées et plus difficiles à diagnostiquer. Elles peuvent survenir plus tardivement après l'introduction du traitement inducteur. La fasciite à éosinophiles est une complication rare mais sévère. Elle évolue souvent après l'arrêt du traitement incriminé. Une douzaine de cas ont été rapportés dans la littérature entre 2016 et 2020, chez des patients traités par Nivolumab, Pembrolizumab, Atézolizumab et Cémiplimab, dans le cadre de néoplasies diverses. L'atteinte des muscles intercostaux n'a, à notre connaissance, jamais été rapportée. Il n'existe actuellement pas de consensus thérapeutique. La discussion de l'arrêt de l'immunothérapie est la règle. La corticothérapie systémique représente le traitement de première ligne, d'emblée ou secondairement associé à un immunosuppresseur, en premier lieu le methotrexate ou autre DMARD. Dans les cas les plus sévères, des cures d'immunoglobulines polyvalentes IV peuvent être proposées. Nous rapportons ici le cas d'une fasciite à éosinophiles secondaires à un traitement par Nivolumab, compliquée d'une atteinte des muscles intercostaux. Cet effet indésirable rare doit être évoqué en cas de développement d'œdèmes durs associés à une éosinophilie, dans le cadre d'un traitement par inhibiteurs du check-point. L'atteinte thoracique est à évoquer en cas de dyspnée inexpliquée dans ce contexte. [ABSTRACT FROM AUTHOR]

Primary cutaneous B cell lymphomas have a high recurrence rate after treatment with surgery and/or local radiation therapy. Two men are described in whom radiotherapy-relapsing cutaneous B-cell lymphomas were successfully treated with the monoclonal anti-CD20 antibody rituximab. Both patients had a complete response with no recurrence at follow-up at 17 and 24 months for the large B-cell lymphoma of the leg and the follicle centre cell lymphoma, respectively. These are two of the few cases in the literature showing that rituximab is an effective and well-tolerated treatment for radiotherapy-relapsing primary cutaneous B cell lymphoma. [ABSTRACT FROM AUTHOR]

Focuses on duodenal and gastric ulcers and gastric cancer caused by Helicobacter pylori infection. Various factors affection outcome of H. pylori infection, including amount of acid secreted by parietal cells; Regulation of gastric acid secretion; H. pylori related acid secretion; Other factors that might affect gastric physiology and disease outcome related to the host, bacterium, and the environment.

The primary aim of this study was to test the equivalence of two fetal weight estimation formulas generated by Hadlock: H1, a formula that includes head circumference (HC) parameter, and H2, which excludes it. Estimated fetal weight (EFW) was calculated using H1 and H2 formulas. [Extracted from the article]

Presents observations on changes that facilitate colonization by Heliobacter pylori and may promote gastric ulcer formation. Gastric mucus barrier; Pathogological implications.