Paired associate learning deficits in poor readers: The contribution of phonological input and output processes.
It is well-established that poor readers exhibit deficits in paired associate learning (PAL), and there is increasing evidence for a phonological locus of these deficits. However, it remains unclear whether poor performance stems from difficulties specific to the phonological output system or difficulties that affect both phonological input and output processes. Understanding these deficits is important not only in the context of PAL but also for informing broader theories of typical and atypical reading development. We developed a novel paradigm that allowed us to assess PAL in the presence and absence of phonological output demands. In total, 14 poor readers and 14 age-matched controls were first trained to criterion in verbal-visual PAL before being tested in the visual-verbal direction. The results showed that poor readers learned at the same rate as controls in verbal-visual PAL, even when the nonword stimuli were phonologically confusable. Yet, despite having reached the same criterion as controls in verbal-visual PAL, poor readers exhibited robust impairments for those same paired associates in visual-verbal PAL. The overall pattern of results is most consistent with the conclusion that PAL deficits reflect impairments to the phonological output system; however, results that may challenge this interpretation are also discussed.


Multipathway Integrated Adjustment Mechanism of Glycyrrhiza Triterpenes Curing Gastric Ulcer in Rats.
Gastric ulcer is a common chronic disease in human digestive system, which is difficult to cure, easy to relapse, and endangers human health seriously. Compared with western medicine, traditional Chinese medicine has a unique advantage in improving the general situation, stablizing medical condition, and with little side effects. Glycyrrhiza known as "king of all the medicine", has a range of pharmacological activities and is commonly used in a variety of proprietary Chinese medicines and formulations. On the basis of explicit antiulcer effect of Glycyrrhiza triterpenes, the molecular mechanisms of its therapeutic effect on acetic acid induced gastric ulcer in rats were explored. Acetic acid induced gastric ulcer model in rats was established to evaluate the curing effect of G. triterpenes and all of the rats were randomised into six groups: Control group, model group, omeprazole group (0.8 mg/mL), triterpenes high dose group (378.0 mg/mL), triterpenes middle dose group (126.0 mg/mL), and triterpenes low dose group (42.0 mg/mL). All rats in groups were orally administered the active group solution 1.5 mL once daily (model and control groups with saline) for 7 days. HPLC-TOF-MS analysis method was performed to obtain the plasma metabolites spectrums of control group, model group, triterpenes high, middle and low dose groups. A total of 11 differential endogenous metabolites related to the therapeutic effect of G. triterpenes were identified, including tryptophan, phingosine-1-phosphate, pantothenic acid, and so on, among which tryptophan and phingosine-1-phosphate are related with the calcium signaling pathway and arachidonic acid (AA) metabolism. At the same time, in order to verify the above results, quantitative real time polymerase chain reaction were performed to evaluate the expression of H+-K+-ATPase alpha mRNA and phospholipase a 2 mRNA in relational signaling pathways. Combined with statistical analysis of plasma metabolic spectrum and gene expression in tissue, it is suggested that G. triterpenes has antiulcer effect on gastric ulcer in rats. G. triterpenes has a certain regulating effect on the metabolism of tryptophan, AA, sphingosine, and other endogenous metabolites, and we speculated that the antiulcer potential of G. triterpenes can be primarily attributed to its inhibiting gastric acid secretion, reducing the release of inflammatory mediators, and protecting gastric mucosa effects to prevent the further development of gastric ulcer. G. triterpenes can obviously relieve the symptoms of gastric ulcer, especially the low dose group.G. triterpenes can effectively regulate the amount of small molecule metablism in gastric ulcer rats in vivo, including tryptophan, phingosine-1-phosphate, etc.G. triterpenes resisting gastric ulcer is probably by regulating arachidonic acid metabolism, sphingosine metabolism, etc.Down-regulation of H+-K+-ATPase alpha subunit mRNA and up-regulation of PLA2 mRNA in gastric tissue of dose group validated the possible mechanisms of G. triterpenes for the treatment of gastric ulcer Abbreviations used: HP: Helicobacter pylori, ECL: enterochromaffinlike, TCM: Traditional Chinese medicine; HPLC: High Performance Liquid Chromatography, HPLC/MS: High Performance Liquid chromatography Mass Spectrometry, HPLC-TOF-MS: High Performance Liquid Chromatography and Tof Mass Spectrometry, SD: Sprague Dawley, PCDL: Personal Compound Database and Library, MPP: Mass Profiler Professiona; PCA: principal component analysis, RT-PCR: real time polymerase chain reaction, PGE 2: Prostaglandin E2, COX1: cyclooxygenase 1 S1P: Sphingosine-1-phosphate, AA: Arachidonic acid, 5-HT: 5- hydroxytryptamine.


Generation and Coherent Control of Pulsed Quantum Frequency Combs.
We present a method for the generation and coherent manipulation of pulsed quantum frequency combs. Until now, methods of preparing high-dimensional states on-chip in a practical way have remained elusive due to the increasing complexity of the quantum circuitry needed to prepare and process such states. Here, we outline how high-dimensional, frequency-bin entangled, two-photon states can be generated at a stable, high generation rate by using a nested-cavity, actively mode-locked excitation of a nonlinear micro-cavity. This technique is used to produce pulsed quantum frequency combs. Moreover, we present how the quantum states can be coherently manipulated using standard telecommunications components such as programmable filters and electro-optic modulators. In particular, we show in detail how to accomplish state characterization measurements such as density matrix reconstruction, coincidence detection, and single photon spectrum determination. The presented methods form an accessible, reconfigurable, and scalable foundation for complex high-dimensional state preparation and manipulation protocols in the frequency domain.


Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of glucose production in women.
Chronic nicotinic acid (NA) ingestion effectively lowers lipid levels, but adverse effects on glucose metabolism have been reported. Our goal was to investigate acute and chronic effects of NA on lipolysis and glucose metabolism in women. Healthy normolipidemic volunteers (n = 5) were studied twice; four-day hospital stays were separated by 1 mo, during which time subjects took increasing doses of NA to 2 g/day (500 mg, 4 times). In the second study, 500 mg of NA was given at 0800. Rates of appearance (R(a)) of free fatty acid (FFA), glycerol, and glucose were determined by isotope dilution (of [1,2,3,4-(13)C(4)]palmitate, [2-(13)C(1)]glycerol, and [U-(13)C(6)]glucose). Mass isotopomer distribution analysis was used to measure gluconeogenesis and glycogenolysis. Fasting FFA concentrations ([FFA]), R(a) FFA, and R(a) glycerol were nonsignificantly elevated after 1 mo. Acute NA induced a significant reduction followed by a rebound overshoot of [FFA], R(a) FFA, and R(a) glycerol. Whole body fat oxidation fell initially and then increased back to basal levels; endogenous glucose production (EGP) increased in parallel with carbohydrate oxidation and then returned to basal values. The increased EGP was due entirely to increased glycogenolysis, not gluconeogenesis. We conclude that chronic effects of NA on FFA metabolism are complex (acute suppression followed by overshoot of R(a) FFA and [FFA] on top of a trend toward basal elevations), that responses after NA are consistent with operation of a glucose-fatty acid cycle in peripheral tissues, and that secondary effects on EGP were through changes in glycogenolysis, not gluconeogenesis.


Perioperative considerations in a newly described subtype of congenital long QT syndrome.
An infant with a newly-described subtype of congenital long QT syndrome is presented, along with her perioperative management on three separate occasions. During each anaesthetic characteristic arrhythmias occurred. The available literature and rational approaches to these high risk patients are reviewed.


A structure-activity study of nociceptin-(1-13)-peptide amide. Synthesis of analogues substituted in positions 0, 1, 3, 4 and 10.
A series of analogues of nociceptin, Noc(1-13)NH(2) (an agonist at the ORL1 receptor) was synthesized with following modifications: (1) N-terminal extension with Arg(0); (2) replacement of Gly(3) by basic or polar amino acids-Arg, Asn, Lys(For) or deletion; (3) exchange of Phe(1) or Phe(4) by Phe(NO(2)); (4) substitution of Ser(10) with D-Ser, Pro, D-Pro. The analogs were synthesized by solid-phase methodology using Fmoc-amino acid pentafluorophenyl esters. The affinity for the ORL1 and for the kappa, micro and delta-opioid receptors was investigated by radioligand binding assay and bioactivity by a mouse vas deferens (MVD) assay. The addition of the amino acid residue Arg to the N-terminal enhances the opioid receptor affinity of Noc(1-13)NH(2) while retaining ORL1 receptor affinity at a moderate level. The replacement of Gly in position 3 by the basic or polar amino acids-Arg, Asn, Lys(For) or its deletion led to inactive analogues. The replacement of Ser in position 10 by its D-isomer, Pro and D-Pro resulted in a series of analogues with the following order of activity: Ser(10)>D-Ser(10)>Pro(10)>D-Pro(10). In [D-Ser(10)]Noc(1-13)NH(2), introduction of an additional Phe(NO(2))(4) led to a >60-fold increase of ORL1 affinity, completely attenuating the loss of affinity brought about by Ser(10). In other analogues, introduction of Phe(NO(2))(4) did not change the magnitude of ORL1 binding significantly. Generally, while modifications in position 3 frequently led to a loss of most or all bioactivity, modifications in position 0 (Arg(0)) or 4 (Phe(NO(2))(4)) and 10 (D-Ser(10), Pro(10)) are tolerated.


Medial prefrontal cortex plays a critical and selective role in 'feeling of knowing' meta-memory judgments.
The frontal lobes are thought to play a role in the monitoring of memory performance, or 'meta-memory', but the specific circuits involved have yet to be definitively established. Medial prefrontal cortex in general and the anterior cingulate cortex in particular, have been implicated in other forms of monitoring, such as error and conflict monitoring. Here, we tested the hypothesis that medial prefrontal cortex plays a critical role in memory monitoring, aiming to determine whether this region contributed to all, or only some classes of meta-memory judgments. We also investigated the relationship between these judgments and memory performance itself. Three types of meta-memory judgment were measured in 5 subjects with focal damage to medial prefrontal cortex, with maximal overlap in dorsal anterior cingulate cortex, compared to 19 healthy, demographically matched control subjects performing a face-name episodic memory task. Judgment-of-learning accuracy was not affected by such damage. In contrast, both recall confidence and feeling-of-knowing judgments were impaired. Memory performance was itself impaired in the patient group, so we performed a second experiment to examine the relationship between memory and meta-memory deficits. In an easier memory task, where patients performed as well as controls, recall confidence accuracy improved to within the control range despite medial prefrontal damage. In contrast, feeling-of-knowing judgments remained less accurate in the patient group. These results argue that medial prefrontal cortex plays a critical role in generating accurate recall confidence and feeling-of-knowing judgments, but is not necessary for judgment-of-learning. The role of this region in feeling-of-knowing seems to be, at least in part, independent of its role in memory itself.


Synergies of fuel cell system thermal management and cryogenic hydrogen exergy utilization.
Low-temperature polymer electrolyte fuel cell systems (FCSs) need to reject large amounts of low temperature heat. Often a mobile FCS's cooling capacity limits the FCS power output. Cryogenic hydrogen is typically utilized as a direct heat sink using heat exchangers (HXs), even though HXs destroy most hydrogen exergy. This paper investigates synergies between FCS thermal management and cryogenic hydrogen exergy utilization in terms of their benchmark performance: the FCS coolant circuit supplies heat at coolant temperature level to a so named reversible cryogenic exergy utilization system (rCEUS) comprised of thermodynamically ideal heat engine processes. The rCEUS converts this heat partly to electrical energy (the value of which equals the hydrogen exergy) and rejects remaining heat to hydrogen to heat it to coolant temperature. The rCEUS output power is used to support the FCS, so the FCS rejects less heat and a significant fraction of this heat is utilized by the rCEUS. As a result, significantly less heat has to be transferred to ambient and the fuel demand decreases. In this paper, three hydrogen storage options are compared: liquid hydrogen, subcooled liquid hydrogen and cryo-compressed hydrogen. Different para- and orthohydrogen compositions are evaluated. For typical FCS operating points, rejected FCS heat to ambient is reducible by 40-67%. FCS power demand is reducible by 14-31%. FCS rejected heat to ambient reduction is 4.5-8 times larger than that of conventional HXs. Calculations are based on hydrogen's lower heating value.


Complex perianal fistulas in Crohn's disease: An anti-TNF α based medico-surgical treatment with magnetic imaging assessment.
Anti-TNFα associated to seton drainage has a central role in the treatment of complex perineal Crohn's fistulas (PAF). A precise treatment protocol is lacking. to evaluate the results of this combined treatment and identify predictive factors of response. It was a retrospective study which included all patients with complex PAF treated with Anti-TNFα. We included 49 patients, mean age of 31.6 years. 17 patients had an active rectal involvement. 35 patients had azathioprin. After the induction, 43 patients had a clinical response. Maintenance therapy was started in 45 cases. After a median of 19 months of Anti-TNFα, 24 patients had a clinical remission (with radiological remission in 20), 17 a partial clinical response, and 4 were in failure. After clinico-radiologic remission setons were removed in all patients, 46% of patients who stopped Anti-TNFα treatment after clinico-radiologic remission relapsed. Absence of rectal involvement and Clinical remission after induction were the independent predictive factors of achieving a clinical remission under maintenance therapy with Anti-TNFα (p=0.016) and clinico-radiological remission (p=0.028). An Anti-TNFα based treatment combined with long term loose seton drainage have contributed to the high rates of both clinical and radiological responses in this study. Obtaining a "deep" clinico-radiological remission should be the target of the treatment. Stopping the Anti-TNFα should be avoided even after obtaining such response.


Marriage and cohabitation in the United States: A statistical portrait based on cycle 6 (2002) of the National Survey of Family Growth.
This report provides an overview of marital and cohabiting relationships in the United States among men and women aged 15-44 in 2002, by a variety of characteristics. National estimates are provided that highlight formal and informal marital status, previous experience with marriage and cohabitation, the sequencing of marriage and cohabitation, and the stability of cohabitations and marriages. The analyses presented in this report are based on a nationally representative sample of 12,571 men and women aged 15-44 living in households in the United States in 2002, based on the National Survey of Family Growth, Cycle 6. Over 40% of men and women aged 15-44 were currently married at the date of interview, compared with about 9% who were currently cohabiting. Men and women were, however, likely to cohabit prior to becoming married. Marriages were longer lasting than cohabiting unions; about 78% of marriages lasted 5 years or more, compared with less than 30% of cohabitations. Cohabitations were shorter-lived than marriages in part because about half of cohabitations transitioned to marriage within 3 years. Variations--often large variations-in marital and cohabiting relationships and durations were found by race and Hispanic origin, education, family background, and other factors.


Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance.
Insulin resistance is instrumental in the pathogenesis of type 2 diabetes mellitus and the Insulin Resistance Syndrome. While insulin resistance involves decreased glucose transport activity in skeletal muscle, its molecular basis is unknown. Since muscle GLUT4 glucose transporter levels are normal in type 2 diabetes, we have tested the hypothesis that insulin resistance is due to impaired translocation of intracellular GLUT4 to sarcolemma. Both insulin-sensitive and insulin-resistant nondiabetic subgroups were studied, in addition to type 2 diabetic patients. Biopsies were obtained from basal and insulin-stimulated muscle, and membranes were subfractionated on discontinuous sucrose density gradients to equilibrium or under nonequilibrium conditions after a shortened centrifugation time. In equilibrium fractions from basal muscle, GLUT4 was decreased by 25-29% in both 25 and 28% sucrose density fractions and increased twofold in both the 32% sucrose fraction and bottom pellet in diabetics compared with insulin-sensitive controls, without any differences in membrane markers (phospholemman, phosphalamban, dihydropyridine-binding complex alpha-1 subunit). Thus, insulin resistance was associated with redistribution of GLUT4 to denser membrane vesicles. No effects of insulin stimulation on GLUT4 localization were observed. In non-equilibrium fractions, insulin led to small GLUT4 decrements in the 25 and 28% sucrose fractions and increased GLUT4 in the 32% sucrose fraction by 2.8-fold over basal in insulin-sensitive but only by 1.5-fold in both insulin-resistant and diabetic subgroups. The GLUT4 increments in the 32% sucrose fraction were correlated with maximal in vivo glucose disposal rates (r = +0.51, P = 0.026), and, therefore, represented GLUT4 recruitment to sarcolemma or a quantitative marker for this process. Similar to GLUT4, the insulin-regulated aminopeptidase (vp165) was redistributed to a dense membrane compartment and did not translocate in response to insulin in insulin-resistant subgroups. In conclusion, insulin alters the subcellular localization of GLUT4 vesicles in human muscle, and this effect is impaired equally in insulin-resistant subjects with and without diabetes. This translocation defect is associated with abnormal accumulation of GLUT4 in a dense membrane compartment demonstrable in basal muscle. We have previously observed a similar pattern of defects causing insulin resistance in human adipocytes. Based on these data, we propose that human insulin resistance involves a defect in GLUT4 traffic and targeting leading to accumulation in a dense membrane compartment from which insulin is unable to recruit GLUT4 to the cell surface.


Environmental complexity influences association network structure and network-based diffusion of foraging information in fish shoals.
Socially transmitted information can significantly affect the ways in which animals interact with their environments. We used network-based diffusion analysis, a novel and powerful tool for exploring information transmission, to model the rate at which sticklebacks (Gasterosteus aculeatus) discovered prey patches, comparing shoals foraging in open and structured environments. We found that for groups in the open environment, individuals tended to recruit to both the prey patch and empty comparison patches at similar times, suggesting that patch discovery was not greatly affected by direct social transmission. In contrast, in structured environments we found strong evidence that information about prey patch location was socially transmitted and moreover that the pathway of information transmission followed the shoals' association network structures. Our findings highlight the importance of considering habitat structure when investigating the diffusion of information through populations and imply that association networks take on greater ecological significance in structured than open environments.


Japanese guidelines for atopic dermatitis 2020.
Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.


In situ localization of tissue factor in human atherosclerotic plaques by binding of digoxigenin-labeled factors VIIa and X.
The mechanism responsible for the thrombotic complications of atherosclerotic plaques is not well understood. Although a role for tissue factor (TF) has been hypothesized, there are scant data on the presence, location, quantity, and activity of TF in atherosclerotic plaques. The purpose of this study was to show the localization of TF in human atherosclerotic plaques. Digoxigenin-labeled factors VIIa and X were used to demonstrate their specific binding sites in formalin-fixed, paraffin-embedded human arteries by incubation of sections with the labeled factor and localization of TF:factor(s) complexes by immunohistochemical staining for digoxigenin. In sections of atherosclerotic plaques, diffuse staining was most intense in the relatively acellular, lipid-rich core but was also present intracellularly in macrophages and smooth muscle cells and, to a lesser extent, in the relatively acellular fibrous tissue of the plaque. Endothelial cells overlying plaques and occasional medial smooth muscle cells stained positively as well. The adventitia routinely stained for TF in both normal and diseased artery segments. Staining for labeled factor VIIa was blocked when sections were preincubated with a 10-fold excess of unlabeled factor VIIa or with a polyclonal antihuman TF antibody. Binding of labeled factors VIIa and X was Ca(2+)-dependent. In conclusion, binding of digoxigenin-labeled factors VIIa and X shows that the lipid rich core of atherosclerotic plaques contains high levels of extracellular TF. This location may be responsible for the rapid initiation of thrombosis when lipid rich atherosclerotic plaques rupture and the core contents are exposed to flowing blood.


Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria.
To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy. Randomised follow up study of normotensive diabetics with persistent microalbuminuria (30-300 mg/24 hours) treated with enalapril or its matched placebo for one year. Double blind for first six months, single blind for last six months. Diabetic clinic in tertiary referral centre. Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria. Treatment group was given enalapril 20 mg daily and controls matched placebo. Patients were given antihypertensive treatment after one year. Albumin excretion, arterial pressure, and renal function. In last three months of trial three of 10 patients taking placebo had diabetic nephropathy (albumin excretion greater than 300 mg/24 hours). No patients taking enalapril developed nephropathy and five showed normal albumin excretion (less than 30 mg/24 hours) (p = 0.005, Mann-Whitney test). Mean arterial pressure was reduced by enalapril throughout study (p less than 0.005) but increased linearly with placebo (p less than 0.05). Albumin excretion decreased linearly with enalapril but not placebo. An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure (r = 0.709, p less than 0.05, Spearman's rank test). With enalapril total renal resistances and fractional albumin clearances improved progressively (time effect, p = 0.0001). Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria. This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure. Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs.


Modeling Electrical Switching of Nonvolatile Phase-Change Integrated Nanophotonic Structures with Graphene Heaters.
Progress in integrated nanophotonics has enabled large-scale programmable photonic integrated circuits (PICs) for general-purpose electronic-photonic systems on a chip. Relying on the weak, volatile thermo-optic, or electro-optic effects, such systems usually exhibit limited reconfigurability along with high-energy consumption and large footprints. These challenges can be addressed by resorting to chalcogenide phase-change materials (PCMs) such as Ge2Sb2Te5 (GST) that provide a substantial optical contrast in a self-holding fashion upon phase transitions. However, current PCM-based integrated photonic applications are limited to single devices or simple PICs because of the poor scalability of the optical or electrical self-heating actuation approaches. Thermal-conduction heating via external electrical heaters, instead, allows large-scale integration and large-area switching, but fast and energy-efficient electrical control is yet to be achieved. Here, we model electrical switching of GST-clad-integrated nanophotonic structures with graphene heaters based on the programmable GST-on-silicon platform. Thanks to the ultra-low heat capacity and high in-plane thermal conductivity of graphene, the proposed structures exhibit a high switching speed of ∼80 MHz and a high energy efficiency of 19.2 aJ/nm3 (6.6 aJ/nm3) for crystallization (amorphization) while achieving complete phase transitions to ensure strong attenuation (∼6.46 dB/μm) and optical phase (∼0.28 π/μm at 1550 nm) modulation. Compared with indium tin oxide and silicon p-i-n heaters, the structures with graphene heaters display two orders of magnitude higher figure of merits for heating and overall performance. Our work facilitates the analysis and understanding of the thermal-conduction heating-enabled phase transitions on PICs and supports the development of future large-scale PCM-based electronic-photonic systems.


The effect of nutritional counselling on diet and plasma EFA status in multiple sclerosis patients over 3 years.
The dietary intake of 83 people with multiple sclerosis (MS) was assessed by the 7-day weighed intake method prior to dietary advice and at 6-monthly intervals thereafter up to 36 months. The P:S ratio of the diet increased from an initial value of 0.8 to 1.5 after 6 months and 1.34 at 36 months. Biochemical investigation of plasma essential fatty acid (EFA) status specifically linoleic, eicosapentanoic and docosahexanoic acids showed significant correlations with diet. Concurrent 6-monthly neurological and physiotherapy assessments were also carried out, the neurological results are discussed in relation to a nutrient scoring system.


e-PainSupport: A Digital Pain Management Application for Home Hospice Care.
e-PainSupport is a digital pain management application (app) designed to facilitate better pain management in hospice. Early testing revealed caregivers found it was easy to use and successful in communicating patient pain and caregiver administration of analgesics to hospice nurses. However, caregiver knowledge of analgesic management remained low. The purpose of this study was to enhance e-PainSupport by (a) adapting and integrating an evidence-based pain educational intervention; (b) increasing ease of accessing and navigating the app; and (c) facilitating app communication with agency electronic health records (EHRs). An advisory board method, including two key stakeholder groups (an expert panel and a caregiver advisory board), guided the adaptation of an evidence-based pain educational intervention. Further, stakeholders recommended format changes to increase app usability. Study staff worked with four hospice agencies to facilitate app communication with EHRs. While modification to the e-PainSupport app to integrate a pain educational intervention and facilitate usability was successful, EHR integration was challenging. Future evaluation is needed to evaluate the effects of e-PainSupport on pain intensity among home hospice patients.


Solution titration by wall deprotonation during capillary filling of silicon oxide nanochannels.
This paper describes a fundamental challenge when using silicon oxide nanochannels for analytical systems, namely the occurrence of a strong proton release or proton uptake from the walls in any transient situation such as channel filling. Experimentally, when fluorescein solutions were introduced into silicon oxide nanochannels through capillary pressure, a distinct bisection of the fluorescence was observed, the zone of the fluid near the entrance fluoresced, while the zone near the meniscus, was dark. The ratio between the zones was found to be constant in time and to depend on ionic strength, pH, and the presence of a buffer and its characteristics. Theoretically, using the Gouy-Chapman-Stern model of the electrochemical double layer, we demonstrate that this phenomenon can be effectively modeled as a titration of the solution by protons released from silanol groups on the walls, as a function of the pH and ionic strength of the introduced solution. The results demonstrate the dominant influence of the surface on the fluid composition in nanofluidic experiments, in transient situations such as filling, and changes in solvent properties such as the pH or ionic strength. The implications of these fundamental properties of silicon oxide nanochannels are important for analytical strategies and in particular the analysis of complex biological samples.


The POU homeobox protein Oct-1 regulates radial glia formation downstream of Notch signaling.
Radial glia cells function as guide cells for neuronal migration and a source of neural progenitor cells, and play a crucial role for the development of the central nervous system. To date, several signals have been demonstrated to promote the formation of radial glia cells and Notch signaling is one such signal. However, the mechanism of the signaling hierarchy of radial glia developmental cascade promoted by Notch signaling still remains incomplete. Here we show that Notch signaling promotes Xenopus radial glia formation and that the Notch activation is sufficient for radial glia formation prior to neural tube closure. Moreover, we have identified Oct-1 (POU2f1), a POU transcription factor, as a downstream target of Notch signaling by microarray based screen. We demonstrate that the expression of Oct-1 in the brain is regulated by Notch signaling and that Oct-1 is sufficient and necessary for radial glia formation. Together, Oct-1 is a downstream effector of Notch signaling during radial glia formation.


TDIOT: Target-Driven Inference for Deep Video Object Tracking.
Recent tracking-by-detection approaches use deep object detectors as target detection baseline, because of their high performance on still images. For effective video object tracking, object detection is integrated with a data association step performed by either a custom design inference architecture or an end-to-end joint training for tracking purpose. In this work, we adopt the former approach and use the pre-trained Mask R-CNN deep object detector as the baseline. We introduce a novel inference architecture placed on top of FPN-ResNet101 backbone of Mask R-CNN to jointly perform detection and tracking, without requiring additional training for tracking purpose. The proposed single object tracker, TDIOT, applies an appearance similarity-based temporal matching for data association. To tackle tracking discontinuities, we incorporate a local search and matching module into the inference head layer that exploits SiamFC. Moreover, to improve robustness to scale changes, we introduce a scale adaptive region proposal network that enables to search for the target at an adaptively enlarged spatial neighborhood specified by the trace of the target. In order to meet long term tracking requirements, a low cost verification layer is incorporated into the inference architecture to monitor presence of the target based on its LBP histogram model. Performance evaluation on videos from VOT2016, VOT2018, and VOT-LT2018 datasets demonstrate that TDIOT achieves higher accuracy compared to the state-of-the-art short-term trackers while it provides comparable performance in long term tracking. We also compare our tracker on LaSOT dataset where we observe that TDIOT provides comparable performance with other methods that are trained on LaSOT. The source code and TDIOT output videos are accessible at https://github.com/msprITU/TDIOT.


X-ray luminescence optical tomography imaging: experimental studies.
We present a hybrid imaging modality, x-ray luminescence optical tomography (XLOT), in which collimated x-ray beams are used to excite phosphor-based contrast agents. Images are reconstructed from the optical signals, using the known x-ray beam location and spatial extent as priors. We demonstrate XLOT using phantom experiments with deep targets and show that the reconstructed signal varies by <12% when the depth changes from 4.2 to 7.7 mm. For simple source distributions, we find as few as two orthogonal projection measurements are sufficient for XLOT reconstruction.


Association of chondromodulin-II Val58Ile polymorphism with radiographic joint destruction in rheumatoid arthritis.
Chondromodulin-II (ChM-II) is a cartilage-derived protein involved in cartilage and bone repair. A study of Japanese patients with rheumatoid arthritis (RA) implicated an association between a 172G --> A (Val58Ile) polymorphism and radiographic damage. We analyzed ChM-II for polymorphisms and investigated the association with radiographically assessed joint destruction in German patients with RA. Possible interactions with the shared epitope (SE) were examined. DNA samples from 204 patients with RA, 81 patients with osteoarthritis, and 116 patients with gout, serving as controls, were sequenced. Radiographic damage was assessed by modified Larsen score. Allele and genotype frequencies between groups were compared by Cochrane-Armitage trend tests. Five missense mutations, one silent mutation, and 5 intronic polymorphisms were found. Allele and genotype frequencies were similar in both disease groups. Larsen scores were significantly higher in RA patients carrying the 172AA (Ile/Ile) genotype (Larsen 96.8), than in RA patients with the 172GA (Val/Ile; Larsen 69.5) or 172GG (Val/Val; Larsen 54.8; p = 0.001) genotypes. Odds ratios to develop more severe radiographic joint damage (Larsen score > 90; above 75th percentile) were 4 and 15.5 for the 172GA and 172AA genotypes, respectively. Presence of a 172A allele increased the risk for enhanced radiographic damage 3-fold. SE and ChM-II 172A alleles emerged as 2 independent risk factors. A potentiated interaction of these risk alleles could not be verified. Our data indicate that ChM-II Val58Ile polymorphism is associated with radiographic progression of joint destruction, particularly in German patients with RA negative for SE.


The opportunity costs of informal care: does gender matter?
In this paper, we investigate the costs borne by both male and female carers in terms of their forgone formal employment opportunities. Traditionally, informal care was supplied by women but nowadays women are not only more likely to work, but also likely to be significant contributors to family finances. For women, this implies that the size of any forgone earnings cost of informal care is increasing. At the same time, population ageing is making for increasing numbers requiring care. From a policy perspective it is therefore helpful to consider a less traditional but nevertheless important source of informal care, men. We find that both male and female carers bear indirect costs in that they are less likely to be in paid work than otherwise similar non-carers and when they are in paid work they earn significantly less. However, we find that the motivation for lower employment participation is not the same for men as it is for women.


Targeting UBR5 inhibits postsurgical breast cancer lung metastases by inducing CDC73 and p53 mediated apoptosis.
UBR5 is a HECT domain E3 ubiquitin ligase that is frequently amplified in breast, ovarian and prostate cancers. Heightened UBR5 expression plays a profound role in tumor growth through immune-dependent mechanisms; however, its mode of action in driving tumor metastasis has not been definitively delineated. Herein, we used a tetracycline (Tet)-inducible RNAi-mediated expression silencing cell system to investigate how UBR5 enables postsurgical mammary tumor metastatic growth in mouse lungs without the continuous influence of the primary lesion. In vitro, Ubr5 knockdown induces morphological and molecular changes characteristic of epithelial-mesenchymal transition (EMT). In vivo, UBR5 promotes lung metastasis in an E3 ubiquitin ligase-dependent manner. Moreover, doxycycline-induced UBR5 expression knockdown in metastatic cells in the lungs, following removing the primary tumors, resulted in increased apoptosis, decreased proliferation and prolonged survival, whereas silencing the expression of cell division cycle 73 (CDC73), a tumor suppressor and E3 ligase substrate of UBR5, reversed these effects. Transcriptome analyses revealed a prominent role of the p53 pathway in dovitinib-induced apoptosis of tumor cells differentially regulated by UBR5 and CDC73. In human triple-negative breast cancer (TNBC) patient specimens, a strong inverse correlation was observed between UBR5 and CDC73 protein levels, with reduced CDC73 expression at metastatic sites compared to primary lesions. Furthermore, a xenograft model of human TNBC recapitulated the metastatic properties and characteristics of the unique UBR5-CDC73 functional antagonism. This study reveals the novel and critical roles and intricate relationships of UBR5, CDC73 and p53 in postsurgical breast cancer metastasis and indicates the potential of targeting this pathway in cancer therapy.


Initiation of direct oral anticoagulants versus warfarin for venous thromboembolism: impact on time to hospital discharge.
The objective of this project was to compare the time from initiation of oral anticoagulation to hospital discharge between warfarin and direct oral anticoagulants (DOACs) for the treatment of acute venous thromboembolism (VTE). This retrospective observational study was done at a single VA medical center. A total of 107 patients were included, with 42 patients (39%) in the DOAC group, which included rivaroxaban, dabigatran, and apixaban, and 65 patients (61%) in the warfarin group. Variables collected through chart review included comorbid conditions, time from initiation of oral anticoagulation to discharge, emergency department (ED) visits and readmission within 30 or 90 days, and bleeding events. The DOAC group had a shorter time to discharge compared to the warfarin group (28 vs. 114 h, p < 0.001). There were similar 30 and 90-day hospital readmission rates and/or ED visits for DOACs (23.8 and 33.3%) compared to warfarin (18.5 and 30.8%), including those related to bleeding of any severity (11.9% for DOACs vs. 9.2% for warfarin; p = 0.75). There was one major bleeding event in the DOAC group and two in the warfarin group. The use of DOACs for the treatment of acute VTE in hospitalized patients was associated with shorter time to hospital discharge when compared to warfarin.


The Cell Wall-Derived Xyloglucan Is a New DAMP Triggering Plant Immunity in Vitis vinifera and Arabidopsis thaliana.
Damage-associated molecular patterns (DAMPs) are endogenous molecules that can activate the plant innate immunity. DAMPs can derive from the plant cell wall, which is composed of a complex mixture of cellulose, hemicellulose, and pectin polysaccharides. Fragments of pectin, called oligogalacturonides (OG), can be released after wounding or by pathogen-encoded cell wall degrading enzymes (CWDEs) such as polygalacturonases (PGs). OG are known to induce innate immune responses, including the activation of mitogen-activated protein kinases (MAPKs), production of H2O2, defense gene activation, and callose deposition. Thus, we hypothesized that xyloglucans (Xh), derived from the plant cell wall hemicellulose, could also act as an endogenous elicitor and trigger a signaling cascade similar to OG. Our results indicate that purified Xh elicit MAPK activation and immune gene expression in grapevine (Vitis vinifera) and Arabidopsis (Arabidopsis thaliana) to trigger induced resistance against necrotrophic (Botrytis cinerea) or biotrophic (Hyaloperonospora arabidopsidis) pathogens. Xh also induce resveratrol production in grapevine cell suspension and callose deposition in Arabidopsis which depends on the callose synthase PMR4. In addition, we characterized some signaling components of Xh-induced immunity using Arabidopsis mutants. Our data suggest that Xh-induced resistance against B. cinerea is dependent on the phytoalexin, salicylate, jasmonate, and ethylene pathways.


Archaeal TFEα/β is a hybrid of TFIIE and the RNA polymerase III subcomplex hRPC62/39.
Transcription initiation of archaeal RNA polymerase (RNAP) and eukaryotic RNAPII is assisted by conserved basal transcription factors. The eukaryotic transcription factor TFIIE consists of α and β subunits. Here we have identified and characterised the function of the TFIIEβ homologue in archaea that on the primary sequence level is related to the RNAPIII subunit hRPC39. Both archaeal TFEβ and hRPC39 harbour a cubane 4Fe-4S cluster, which is crucial for heterodimerization of TFEα/β and its engagement with the RNAP clamp. TFEα/β stabilises the preinitiation complex, enhances DNA melting, and stimulates abortive and productive transcription. These activities are strictly dependent on the β subunit and the promoter sequence. Our results suggest that archaeal TFEα/β is likely to represent the evolutionary ancestor of TFIIE-like factors in extant eukaryotes.


Remote Stewardship for Medically Underserved Nurseries: A Stepped-Wedge, Cluster Randomized Study.
Antibiotic overuse is associated with adverse neonatal outcomes. Many medically underserved centers lack pediatric antibiotic stewardship program (ASP) support. Telestewardship may mitigate this disparity. Authors of this study aimed to determine the effectiveness and safety of a nursery-specific ASP delivered remotely. Remote ASP was implemented in 8 medically underserved newborn nurseries using a stepped-wedge, cluster-randomized design over 3 years. This included a 15-month baseline period, a 9-month "step-in" period using random nursery order, and a 12-month postintervention period. The program consisted of education, audit, and feedback; and 24/7 infectious diseases provider-to-provider phone consultation availability. Outcomes included each center's volume of antibiotic use and the proportion of infants exposed to any antibiotics. Safety measures included length of stay, transfer to another facility, sepsis, and mortality. During the study period, there were 9277 infants born (4586 preintervention, 4691 postintervention). Infants exposed to antibiotics declined from 6.2% pre-ASP to 4.2% post-ASP (relative risk 0.68 [95% confidence interval, 0.63% to 0.75%]). Total antibiotic use declined from 117 to 84.1 days of therapy per 1000 patient-days (-28% [95% confidence interval -22% to -34%]. No safety signals were observed. Most provider-to-provider consultations were <5 minutes in duration and occurred during normal business hours. The number of infants exposed to antibiotics and total antibiotic use declined in medically underserved nurseries after implementing a remote ASP. No adverse safety events were seen, and the remote ASP time demands were manageable. Remote stewardship may be a safe and effective strategy for optimizing antibiotic use in medically underserved newborn nurseries.


Successful treatment with praziquantel of six patients infected with the African lung fluke, Paragonimus uterobilateralis.
Six cases of human paragonimiasis (Paragonimus uterobilateralis) are documented from Liberia and Guinea. These are the first cases reported from these countries. Paragonimiasis should be considered in the differential diagnosis of any West African patient who presents with hemoptysis. Praziquantel was used successfully to treat these patients, and may be the drug of choice for P. uterobilateralis infections.


Discussions on the hepatic well-stirred model: Re-derivation from the dispersion model and re-analysis of the lidocaine data.
Roberts and Rowland explained the well-stirred model as an extreme case of the dispersion model when the dispersion number is infinity. However, the inconsistency within and discrepancy between the theoretical explanation and experimental observations of the well-stirred model are discovered. In this paper, the well-stirred model is examined from both mathematical and physiological points of view. The well-stirred model is re-derived from the convection-elimination equation using the finite difference method. The well-stirred model is a subset of the parallel-tube model when the dispersion number is zero and concentration gradient is ignored. The relative errors and sensitivities of the well-stirred and the parallel-tube models are compared using numerical simulations. The well-stirred model should not be used to estimate in vivo apparent intrinsic clearance from hepatic extraction ratio for high extraction ratio drugs and predicting availability is not recommended for high extraction ratio drugs with either the well-stirred or the parallel-tube models. Based on our theoretical derivation and numerical simulations, we found lidocaine data analysis in Pang and Rowland's 1977 paper was based on an unfair comparison of these two models at two different efficiency number ranges. The high sensitivity of the parallel-tube model at a relatively lower efficiency number range versus the lack of sensitivity of the well-stirred model at an extremely high efficiency number range leads one to believe that the well-stirred model fit the data of high extraction ratio drugs such as lidocaine better. However, the intrinsic clearance values estimated by the parallel-tube model are much more consistent with both in vitro data and those estimated by the dispersion model than those by the well-stirred model. In addition, a key assumption used in the data analysis that the intrinsic clearance is independent of changes in blood flow may not be true. Both theoretical discussions and experimental results indicate that apparent intrinsic clearance and intrinsic clearance could be affected by blood flow and protein binding. Moreover, the lidocaine data analysis in 1977 paper could be control condition dependent and misleading when it is applied to data from other drugs, such as diazepam and diclofenac. The distinction between the well-stirred and parallel-tube models is a result of the mathematical treatment of concentration gradient rather than the flow pattern or extent of physical mixing. The well-stirred model is not likely better than the parallel-tube model. One should be cautious of using the well-stirred model for comparing in vitro intrinsic clearance and estimated in vivo "intrinsic clearance" for high clearance drugs.


Inhibition of Myosin ATPase activity by halogenated pseudilins: a structure-activity study.
Myosin activity is crucial for many biological functions. Strong links have been established between changes in the activity of specific myosin isoforms and diseases such as cancer, cardiovascular failure, and disorders of sensory organs and the central nervous system. The modulation of specific myosin isoforms therefore holds a strong therapeutic potential. In recent work, we identified members of the marine alkaloid family of pseudilins as potent inhibitors of myosin-dependent processes. Here, we report the crystal structure of the complex between the Dictyostelium myosin 2 motor domain and 2,4-dichloro-6-(3,4,5-tribromo-1H-pyrrole-2-yl)phenol (3). Detailed comparison with previously solved structures of the myosin 2 complex with bound pentabromopseudilin (2a) or pentachloropseudilin (4a) provides insights into the molecular basis of the allosteric communication between the catalytic and the allosteric sites. Moreover, we describe the inhibitory potency for a congeneric series of halogenated pseudilins. Insight into their mode of action is gained by applying a combination of experimental and computational approaches.


Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization.
We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3,000 study participants. The model and scripts described here are freely available through CentileBrain ( https://centilebrain.org/ ).


Streptomyces yangpuensis sp. nov., isolated from soil.
A novel Gram-stain-positive strain with sandy aerial mycelium and golden yellow substrate mycelium, designated fd2-tbT, was isolated from a soil sample collected in Shanghai, China, and its taxonomic status was established by phylogenetic analysis. 16S rRNA gene sequence analysis showed that strain fd2-tbT belonged to the genus Streptomyces and was related to Streptomyces amritsarensis JCM 19660T (99.9 % 16S rRNA gene sequence similarity), Streptomyces flavotricini NBRC 12770T (99.9 %), Streptomyces polychromogenes NBRC 13072T (99.8 %), Streptomyces racemochromogenes NRRL B-5430T (99.7 %), Streptomyces globosus LMG 19896T (99.5 %), Streptomyces toxytricini NBRC 12823T (99.5 %) and Streptomyces katrae NBRC 13447T (99.3 %). The cell wall of strain fd2-tbT contained ll-diaminopimelic acid, and whole-cell sugars were identified as glucose and ribose. The menaquinones MK-9(H4), MK-9(H6) and MK-9(H8) were also detected. In addition, the polar lipids diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, as well as five unidentified phospholipids, were detected. Major cellular fatty acids were identified as anteiso-C15 : 0, iso-C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and C16 : 0. DNA-DNA hybridization experiments showed that strain fd2-tbT exhibited 36.5 ± 0.6 %, 43.5 ± 2.0 %, 11.1 ± 1.3 %, 10.3 ± 3.1 %, 9.8 ± 1.9 %, 48.9 ± 3.9 % and 16.3 ± 1.7 % relatedness to S. amritsarensis JCM 40119660T, S. flavotricini NBRC 12770T, S. polychromogenes NBRC 13072T, S. racemochromogenes NRRL B-5430T, S. globosus LMG 19896T, S. toxytricini NBRC 12823T and S. katrae NBRC 13447T, respectively. Based on these analyses as well as some phenotypic differences, strain fd2-tbT is considered to represent a novel species of the genus Streptomyces, for which the name Streptomyces yangpuensis sp. nov. is proposed. The type strain is fd2-tbT ( = DSM 100336T = CGMCC 4.7256T).


Workforce safety in the remote health sector of Australia: a scoping review.
To scope the evidence surrounding workplace health and safety risks for the remote health workforce in Australia and to collate the recommendations to address those risks. A five-stage scoping review framework refined by Cooper et al was used for this review. Informit Health Collection, Ovid Emcare, Medline, Web of Science Core Collection, ProQuest and the grey literature were searched in October 2020 using a combination of key words derived from the eligibility criteria. No date restriction was placed on the search. Title and abstract screening, full-text review and data extraction were performed by three reviewers. Data were analysed by the lead author using qualitative thematic analysis. Articles were eligible for inclusion if they were published research or industry reports, focused on safety for the remote health workforce in Australia, identified hazards/safety risks or recommendations to reduce risk, and were written in English. The search yielded 312 articles, of which 18 met the inclusion criteria. A wide range of hazards/safety risks and recommendations were identified within the literature, which related to safety culture, isolation, safe environment, and education and training. Some recommendations, such as the use of a risk management approach, good post-incident support, safer clinics and accommodation, and improved access to education and training, had been discussed in the literature for over a decade, with a high level of agreement regarding their importance. Two articles briefly evaluated the impact of some recommendations. While many recommendations have been developed to improve the safety of the remote health workforce in Australia, there is little evidence of their implementation and evaluation. As many remote health professionals report ongoing or worsening workplace safety issues, there is an urgent need for the implementation and evaluation of the workforce safety strategies recommended in the literature and required by legislation.


Comparative Effects of 4 Single-Leg Squat Exercises in Subjects With Gluteus Medius Weakness.
Of the weight-bearing exercises, single-leg squats (SLSs) represent one of the most commonly used hip-strengthening exercises that require more gluteus medius (GMED) activity. To date, no studies have investigated how the 4 SLS exercises affect muscle imbalance of GMED, tensor fasciae latae (TFL), and adductor longus (AL), and kinematics of hip. To investigate the hip muscle activities, onset time, and kinematics during 4 different SLS exercises (unilateral squat, unilateral wall-squat [UWS], lateral step-down, and front step-down) in subjects with GMED weakness. Repeated-measures experimental design. Research laboratory. Twenty-two subjects (11 males and 11 females) participated in this study and were compared using 1-way repeated-measures analysis of variance. Surface electromyography was used to measure the muscle activities and onset time of the GMED, TFL, and AL, and 3-dimensional motion tracking system was used to measure the hip adduction and internal/external rotation angles during SLS exercises. One-way repeated-measures analysis of variance was used at a significance level of P < .05. The UWS produced higher GMED/TFL activity ratio and lower GMED/TFL onset time ratio than in the other 3 exercises (P < .05). No difference in GMED/AL activity ratio and GMED/AL onset time ratio was observed. The hip adduction angle was greater in UWS than in the other 3 exercises (P < .05). As for the hip internal/external rotation, lateral step-down exhibited higher hip internal rotation angle than front step-down (P < .05). The UWS may be recommended as an effective exercise for the subjects with GMED weakness, but they should take care to avoid excessive hip adduction during the exercise.


Atropisomeric amides as chiral ligands: using (-)-sparteine-directed enantioselective silylation to control the conformation of a stereogenic axis
An enantiomerically pure (1-trimethylsilyl)ethyl group, constructed by a (-)-sparteine-directed enantioselective quench of a laterally lithiated tertiary aromatic amide, exerts powerful thermodynamic control over the conformation of the adjacent tertiary amide substituent. Ortholithiation and functionalization of the amide in the 6-position allows the single amide conformer to be trapped as an enantiomerically and diastereoisomerically pure amide atropisomer. Protodesilylation of the amide gives functionalized atropisomeric amides with a stereogenic axis of single absolute configuration, whose barriers to racemization have been determined by polarimetry. Enantiomerically pure amides bearing phosphine substituents are effective ligands in a Pd-catalyzed allylic substitution reaction-the first use of a nonbiaryl atropisomer as a chiral ligand-and give products with 90% ee. The rate of racemization of the phosphine-substituted amide is powerfully influenced by the presence of palladium.


Students in Danger: Binge Drinking Behaviour and Associated Factors in Hungary.
Among young adults, high rates of binge drinking were observed in certain European countries. Binge drinking is associated with several health problems (unplanned pregnancy, HIV infections, problems with memory, and injuries). The aim of this questionnaire-based study was to measure the frequency of binge drinking and its association with sociodemographic, familial, lifestyle factors and school performance among secondary and university students (n=2449) in Csongrád County, Hungary. In this cross-sectional study the students' sociodemographic data, parents' educational and economic level, and students' academic performance and self-reported use of tobacco, drugs, and alcohol were collected by a questionnaire. Descriptive statistics and multivariable binary logistic regression analyses were applied using SPSS 24.0 software. Altogether 2449 Hungarian secondary school students and university students participated in the study. Nearly one-third of the students were classified as binge drinkers, significantly more male university students. Tobacco or illicit drug use resulted in higher odds of being a binge drinker in both subgroups. Poor school performance and binge drinking were significantly correlated especially among secondary school students. Targeting alcohol, tobacco, and illicit drug use together, including education, parent interventions, and public health policies, are crucial in the prevention of possible serious consequences.


Is the daily use of vacuum erection device for a month before penile prosthesis implantation beneficial? a randomized controlled trial.
Patient concerns about penile length after penile prosthesis (PP) implantation for erectile dysfunction (ED) have significant impact on patients and their partners. In addition, corporal fibrosis is associated with difficult PP implantation. The preoperative use of vacuum erectile devices (VED) is an uncommon physical treatment for such concerns. Therefore, the current randomized controlled study assessed two outcomes: whether pre-operative VED use for a month before surgery would significantly increase flaccid stretched penile length (SPL) on the day of surgery, and facilitate easier corporal dilatation intraoperatively. Fifty-one patients scheduled for PP implantation for ED were randomized to either intervention group (pre-operative VED use; 10-15 min/day for ≥30 days; Group A; n = 25), or control group (no intervention; Group B; n = 26). A research assistant (blinded to the treatment assignments) recorded SPL at baseline (initial consultation) and on day of surgery. The surgeons performing the PP implantation (also blinded to the treatment assignments) provided subjective assessments of the ease of corporal dilatation. Baseline patient characteristics, demographics, and comorbidities were the same in both groups. Baseline measurements (SPL-1) were 10.71 ± 1.28 and 10.87 ± 1.26 cm in Group A and Group B, respectively; and the day of surgery measurements (SPL-2) were 11.50 ± 1.33 and 11.06 ± 1.34 cm in Group A and Group B, respectively. In terms of outcomes: mean SPL increase in Group A was significantly more by a mean of 0.80 ± 0.38 cm (p < 0.05) compared to Group B; and surgeons' subjective report of surgical ease indicated smoother corporal dilatation for Group A compared to Group B. VED use (10-15 min/day during the month prior to PP implantation) was associated with significantly increased SPL on day of surgery, and facilitated easier corporal dilatation intraoperatively. Future studies should examine the long-term outcomes of penile prosthesis implantation after pre-operative use of vacuum erectile devices.


The cancer-natural killer cell immunity cycle.
Immunotherapy with checkpoint blockade induces rapid and durable immune control of cancer in some patients and has driven a monumental shift in cancer treatment. Neoantigen-specific CD8+ T cells are at the forefront of current immunotherapy strategies, and the majority of drug discovery and clinical trials revolve around further harnessing these immune effectors. Yet the immune system contains a diverse range of antitumour effector cells, and these must function in a coordinated and synergistic manner to overcome the immune-evasion mechanisms used by tumours and achieve complete control with tumour eradication. A key antitumour effector is the natural killer (NK) cells, cytotoxic innate lymphocytes present at high frequency in the circulatory system and identified by their exquisite ability to spontaneously detect and lyse transformed or stressed cells. Emerging data show a role for intratumoural NK cells in driving immunotherapy response and, accordingly, there have been renewed efforts to further elucidate and target the pathways controlling NK cell antitumour function. In this Review, we discuss recent clinical evidence that NK cells are a key immune constituent in the protective antitumour immune response and highlight the major stages of the cancer-NK cell immunity cycle. We also perform a new analysis of publicly available transcriptomic data to provide an overview of the prognostic value of NK cell gene expression in 25 tumour types. Furthermore, we discuss how the role of NK cells evolves with tumour progression, presenting new opportunities to target NK cell function to enhance cancer immunotherapy response rates across a more diverse range of cancers.


Neutral detergent fiber, hemicellulose and cellulose digestibility in human subjects.
The fate of dietary fiber and its components was examined in seven women consuming low cellulose (LC) and high cellulose (HC) diets, each for about 1 month. The diets were of constant daily composition and differed only in that the HC diet contained an additional 16 g/day non-nutritive fiber (Solka Floc), which increased the neutral detergent fiber (NDF) of the diet from 9.5 to 23.5 g/day and Crampton and Maynard cellulose from 5.4 to 19.3 g/day. When apparent fiber digestibilities during 5-day periods were determined, both NDF and cellulose digestibilities varied greatly and inconsistently in each subject throughout both diet periods. Therefore, samples were pooled to form a single 20-30 day composite for each subject during each diet. Mean apparent NDF digestibility, after correcting for protein contamination in fecal NDF, was 70.4 +/- 7.3% during the LC diet and decreased to 23.0 +/- 15.0% during the HC diet. Cellulose digestibility was 69.7 +/- 10.7% without and 15.7 +2- 17.4% with the added cellulose. Hemicellulose was calculated as NDF minus cellulose. When the fecal NDF was corrected for protein contamination, hemicellulose digestibility averaged 71.7 +/- 5.4% during the LC diet and 51.0 +/- 7.9% during the HC diet. In a separate experiment, 16 g/day Solka Floc was ingested with a semi-purified liquid diet and only 8% of the cellulose was digested. These results suggest that more than half of the fiber in a LC diet containing fruits, vegetables and refined grains is degraded, while the apparent digestibility of refined cellulose is minimal.


Maternal and Neonatal Outcomes of Gunshot Wounds in Pregnancy: A Systematic Review of Case Reports.
A systematic review was performed to compare adverse maternal and neonatal outcomes among pregnant patients with gunshot wounds (GSW) to the abdominopelvic vs other region(s) at > 20 weeks gestation. A search of Medline Ovid, Elsevier Embase, EBSCO CINAHL, and Cochrane Library in July 2022 and reference searches resulted in 1742 studies, which were screened. The 41 included studies reported outcomes for 59 pregnant patients with GSW, of which 31 (52.5%) had an isolated abdominopelvic GSW and 28 (47.5%) had an extremity, thorax, head/neck, back/spine, poly-site, or other/unknown GSW. Stillbirth occurred in 26.7% of abdominopelvic GSW and 26% of non-abdominopelvic GSW. Maternal death occurred in 3.7% of abdominopelvic GSW and 10.7% of non-abdominopelvic GSW. Neonatal death occurred in 9.1% of abdominopelvic GSW and 5.3% of non-abdominopelvic GSW. Further research is needed to standardize the approach for the evaluation and management of patients with GSW in pregnancy.


An examination of the inhibitory effects of N-iodoacetylglucosamine on Escherichia coli and isolation of resistant mutants.
1. After incubation of Escherichia coli with N-iodo[1,2-(14)C(2)]acetylglucosamine, 95-99% of the (14)C taken up by whole cells is located in a cold-trichloroacetic acid-soluble fraction. Two major components of this fraction are S-carboxymethylcysteine and S-carboxymethylglutathione. The same compounds accumulate during incubation with iodo[(14)C]acetate but not with iodo[(14)C]acetamide. The amount of (14)C associated with a cold-trichloroacetic acid-insoluble fraction are comparable for all three alkylating agents. After incubation with iodo[(14)C]acetamide, 50% of the label bound to whole cells is recoverable in a cold-trichloroacetic acid-insoluble fraction. 2. Uptake and incorporation of (14)C from [U-(14)C]glycerol is blocked at an early stage by N-iodoacetylglucosamine. No specific inhibition of macromolecular synthesis could be demonstrated. 3. Mutants selected for resistance to iodoacetate are partially resistant to iodoacetate and N-iodoacetylglucosamine, but show no resistance to iodoacetamide. 4. Mutants selected for resistance to N-iodoacetylglucosamine are not resistant to iodoacetate or iodoacetamide, and are defective in their ability to grow on N-acetylglucosamine. Resistance to N-iodoacetylglucosamine is not absolute, and depends on the presence of glucose or certain other sugars; there is no resistance during growth on maltose, glycerol or succinate. 5. Absolute resistance can be achieved by selecting for a second mutation conferring resistance during growth on maltose; double mutants isolated by this procedure are unable to grow on N-acetylglucosamine and grow poorly on glucosamine. Resistant single mutants have a slightly diminished uptake of N-acetyl[1-(14)C]glucosamine, but in resistant double mutants the uptake of both [1-(14)C]glucosamine and N-acetyl[1-(14)C]glucosamine is severely diminished. 6. These observations are consistent with the presence of two permeases for N-acetylglucosamine, one that also permits uptake of glucosamine and another that allows entry of methyl 2-acetamido-2-deoxy-alpha-d-glucoside. N-Iodoacetylglucosamine can gain entry to the cell by both permeases.


Photobiomodulation therapy associated with supervised therapeutic exercises for people with knee osteoarthritis: a randomised controlled trial protocol.
Physical exercise, a cornerstone of the conservative management of knee osteoarthritis (KOA), is exhaustively recommended by important clinical guidelines. A strength therapeutic exercise program (STEP) relieves pain, improves physical function and ultimately ameliorates quality of life (QoL). Furthermore, photobiomodulation (PBM) has been used as an adjunct treatment for people with KOA; however, there are still controversial recommendations regarding its use on this population. Thus, we hypothesised that PBM, when associated with a STEP protocol on patients with KOA, could induce better clinical outcomes than a STEP protocol alone. The study is a 6-month triple-blind placebo-controlled randomised clinical trial with intention-to-treat analysis. The trial will include 120 people with clinic and radiographic signs of KOA. The intervention consists of a supervised STEP and PBM protocols conducted over an 8-week intervention period. Assessments are performed at baseline, right after treatment, and 3-month and 6-month follow-up periods. The primary clinical outcome is pain intensity according to a 10 cm Visual Analogue Scale. Secondary outcomes are the global Western Ontario & McMaster Universities Osteoarthritis Index; QoL assessed by the 36-item Short-Form health survey questionnaire; and performance-based physical parameters assessed by the 30 s chair stand test; the stair climb test; and the 40 m fast-paced walk test. The trial was approved by the Human Research Ethics Committee of the Federal University of São Carlos, São Paulo, Brazil (REC no 2.016.122). Results will be published in peer-reviewed journals. Brazilian Clinical Trials Registry (U1111-1215-6510).


Sclerosing inflammatory pseudotumor of the eye.
We report the clinical course and pathologic findings in a case of intraocular sclerosing inflammatory pseudotumor in a 21-year-old man. The patient initially had a unilateral right interstitial keratitis, scleritis, uveitis, ciliary body mass, and retinal detachment. Scleral and vitreous biopsy specimens revealed an inflammatory process. The eye was eventually enucleated despite therapy with high doses of prednisone and ciprofloxacin hydrochloride. Histologic examination of the globe showed nongranulomatous, acute (neutrophils) and chronic (lymphocytes and histiocytes) inflammation with proliferation of fibrous tissue within the vitreous cavity, uvea, sclera, and contiguous orbital fibroadipose tissue. The contralateral eye later developed a similar mass that resolved following aggressive and prolonged immunosuppressive therapy with retention of 20/16 visual acuity.


Preoperative gait patterns and BMI are associated with tibial component migration.
There is no standard for patient triage in total knee arthroplasty (TKA) based on joint functional characteristics. This is largely due to the lack of objective postoperative measurement of success in TKA in terms of function and longevity, and the lack of knowledge of preoperative metrics that influence outcome. We examined the association between the preoperative mechanical environment of the patients knee joint during gait and the post-TKA stability of the tibial component as measured with radiostereometric analysis (RSA). 37 subjects were recruited out of a larger randomized RSA trial. 3-dimensional gait analysis was performed in the preoperative week. Longitudinal RSA data were gathered postoperatively at 6 months and 1 year. We found a statistically significant association between the pattern of the knee adduction moment during gait preoperatively and the total migration of the implant at 6 months postoperatively. A substantial proportion of the variability in the total postoperative tibial component migration (R(2) = 0.45) was explained by a combination of implant type, preoperative knee joint loading patterns during gait, and body mass index at 6 months postoperatively. The relationships did not remain statistically significant at 1 year postoperatively. Our findings support the hypothesis that preoperative functional characteristics of patients, and particularly joint loading patterns during activities of daily living, are important for outcome in TKA. This represents a first step in the development of predictive models of objective TKA outcome based on preoperative patient characteristics, which may lead to better treatment strategies. ClinicalTrials.gov (NCT00405379).


Modeling and subjective assessment of cell discard in ATM video.
Measurements of subjective picture impairment as a function of network loading in a simulated ATM network are reported. The simulation indicated that cells tend to be discarded in bursts, the frequency and severity of which can be related to the loading by a threshold model. The effect of the discards on broadcast-style video, coded using a single-layer H.261-type method, was found to be a function of scene content and movement at the instant of occurrence. If the visibility of cell discards is maintained at or below threshold in worst-case scenes, the study indicated that network loadings around 55% for a multiplex of 16 video sources and around 70% for a multiplex of 48 video sources are achievable.


Responses of the normal rat kidney to sequential ischemic events.
This study was undertaken to help define how one episode of renal ischemia, insufficient to cause acute renal failure, influences the susceptibility of the kidney to a second more severe ischemic event. Female Sprague-Dawley rats underwent either 15 min of bilateral renal artery occlusion (RAO) or sham RAO. They were subjected 30 min, 3.5 h, or 24 h later to 25 min of RAO. Renal function (GFR, BUN, creatinine), histology, and adenine nucleotide concentrations were compared before and after the 25-min ischemic event. Only the rats with a 30-min hiatus between the 15- and 25-min bouts of RAO had significantly worse renal failure than controls subjected to a single 25-min ischemic event. Three findings were noted only in the rats with increased susceptibility: tubular cell swelling and luminal membrane injury prior to 25 min of RAO and a relative failure of ATP formation immediately following 25 min of RAO. Susceptibility to 25 min of RAO did not correlate with preischemia ATP content. prior mild ischemic injury transiently lowers renal resistance to a second ischemic event. Normal resistance is rapidly restored once improvements in prior cell membrane injury, cell volume regulation, and cellular energetics occur. However, resistance to additional ischemia can be normal despite persisting depressions in renal ATP content.


The acceptability of an investigational vaginal microbicide, PRO 2000 Gel, among women in a phase I clinical trial.
Vaginal microbicides will provide a woman-initiated prevention strategy that could substantially reduce rates of HIV infection. The acceptability of microbicides will greatly influence the use and, hence, effectiveness of such products. In this study, the acceptability of an investigational microbicide, PRO 2000 Gel (Indevus Pharmaceuticals, Inc., Lexington, MA), was assessed, and women's opinions about microbicides and their potential for real world use were gathered. Quantitative and qualitative data were collected from 30 U.S. and 33 South African women. All sexually active HIV-uninfected women and all sexually abstinent HIV-infected women participating in this phase I clinical trial stated in a survey that they would use PRO 2000 Gel if they had reason to be concerned about HIV and the product were available. Qualitative data, however, provided insight into the nuances of acceptability ratings. Women rated product safety, ease of use, and positive effects on sexual pleasure among the most important characteristics of acceptable microbicides. Opinions regarding product leakage, contraceptive capability, and the ability to be used without partners noticing, as well as characteristics of the product itself, varied substantially based on the context of sex and perceptions of risk within each individual woman's life. As microbicide development continues and the first investigational products move into efficacy trials, the needs and preferences of those women who constitute the potential users of microbicides become paramount. Providing woman-initiated microbicides that are safe, easy to use, and pleasurable will be key to the impact these products will have on the AIDS epidemic worldwide.


Changes in plasma motilin concentration in response to manipulation of intragastric and intraduoduenal contents in man.
Immunoreactive plasma motilin concentrations were studied following a variety of stimuli in 24 healthy fasting subjects. Plasma motilin was measured by a radioimmunoassay using antibody GP 71 (J. C. Brown) and natural porcine motilin as standard. Basal motilin levels ranged from undetectable to 365 pg/mL. Antral and intraduodenal infusion of 50 mL o.1 N HCl (pH 1.2) at 5 mL/min failed to alter significantly plasma motilin levels but duodenal acid infusions at 17 mL/min caused a significant increase (70.8 +/- 29.5 pg/mL, mean +/- SEM; n = 6), maximal at 40 min. Duodenal alkalinization with 50 mL 0.3 M Tris buffer (pH 8.0) infused at 5 mL/min produced no change in plasma motilin. A mixed meal did not affect plasma motilin levels. Ingestion of 60 g fat significantly increased plasma motilin (n = 13; maximal increase 150.3 +/- 43.3 pg/mL at 30 min) but duodenal infusions of fat failed to increase plasma motilin levels. These results suggest that motilin secretion induced by fat requires that the fat be present initially within the stomach for secretion to occur. We conclude that ingested fat is a potent stimulus of motilin release. As duodenal acidification (50 mL 0.1 N HCl over 10 min) induces duodenal activity resembling migrating motor complexes but does not release motilin, our data argue against the release of motilin following duodenal acidification as a trigger for the initiation of these complexes in man.


Studies on biological effects of ion beams on lethality, molecular nature of mutation, mutation rate, and spectrum of mutation phenotype for mutation breeding in higher plants.
Recently, heavy ions or ion beams have been used to generate new mutants or varieties, especially in higher plants. It has been found that ion beams show high relative biological effectiveness (RBE) of growth inhibition, lethality, and so on, but the characteristics of ion beams on mutation have not been clearly elucidated. To understand the effect of ion beams on mutation induction, mutation rates were investigated using visible known Arabidopsis mutant phenotypes, indicating that mutation frequencies induced by carbon ions were 20-fold higher than by electrons. In chrysanthemum and carnation, flower-color and flower-form mutants, which are hardly produced by gamma rays or X rays, were induced by ion beams. Novel mutants and their responsible genes, such as UV-B resistant, serrated petals and sepals, anthocyaninless, etc. were induced by ion beams. These results indicated that the characteristics of ion beams for mutation induction are high mutation frequency and broad mutation spectrum and therefore, efficient induction of novel mutants. On the other hand, PCR and sequencing analyses showed that half of all mutants induced by ion beams possessed large DNA alterations, while the rest had point-like mutations. Both mutations induced by ion beams had a common feature that deletion of several bases were predominantly induced. It is plausible that ion beams induce a limited amount of large and irreparable DNA damage, resulting in production of a null mutation that shows a new mutant phenotype.


Exploring important influences on the healthfulness of prostate cancer survivors' diets.
A cancer diagnosis is often conceptualized as a teachable moment when individuals might be motivated to make lifestyle changes. Many prostate cancer survivors, however, do not adhere to dietary guidelines. In this article, we explore how cancer affected prostate cancer survivors' diets and identify important influences on diet. Twenty prostate cancer survivors completed three 24-hour dietary recalls and an in-depth dietary interview. We analyzed interviews using a constant comparison approach, and dietary recall data quantitatively to assess quality and qualitatively to identify food choice patterns. Most men reported not making dietary changes following their cancer diagnosis but did express an interest in healthy eating, primarily to facilitate weight loss. Men portrayed barriers to healthy eating that often outweighed their motivation to eat healthy. Public health programs should consider alternative ways of framing healthy eating programs for prostate cancer survivors that might be more effective than a cancer-specific focus.


Modelling the relationship between peripheral blood pressure and blood volume pulses using linear and neural network system identification techniques.
The relationships between peripheral blood pressure and blood volume pulse waveforms can provide valuable physiological data about the peripheral vascular system, and are the subject of this study. Blood pressure and volume pulse waveforms were collected from 12 normal male subjects using non-invasive optical techniques, finger arterial blood pressure (BP, Finapres: Datex-Ohmeda) and photoelectric plethysmography (PPG) respectively, and captured to computer for three equal (1 min) measurement phases: baseline, hand raising and hand elevated. This simple physiological challenge was designed to induce a significant drop in peripheral blood pressure. A simple first order lag transfer function was chosen to study the relationship between blood pressure (system input) and blood volume pulse waveforms (system output), with parameters describing the dynamics (time constant, tau) and input-output gain (K). Tau and K were estimated for each subject using two different system identification techniques: a recursive parameter estimation algorithm which calculated tau and K from a linear auto-regressive with exogenous variable (ARX) model, and an artificial neural network which was trained to learn the non-linear process input-output relationships and then derive a linearized ARX model of the system. The identification techniques allowed the relationship between the blood pressure and blood volume pulses to be described simply, with the neural network technique providing a better model fit overall (p < 0.05, Wilcoxon). The median falls in tau following the hand raise challenge were 26% and 31% for the linear and neural network based techniques respectively (both p < 0.05, Wilcoxon). This preliminary study has shown that the time constant and gain parameters obtained using these techniques can provide physiological data for the clinical assessment of the peripheral circulation.


Formononetin promotes cell cycle arrest via downregulation of Akt/Cyclin D1/CDK4 in human prostate cancer cells.
Formononetin is an O-methylated isoflavone isolated from the root of Astragalus membranaceus. It has already been reported that formononetin could inhibit cell proliferation and induce cell apoptosis in several cancers, including prostate cancer. This study aimed to further investigate whether cell cycle arrest is involved in formononetin-mediated antitumor effect in human prostate cancer cells, along with the underlying molecular mechanism. Human prostate cancer cells PC-3 and DU145 were respectively treated with various concentrations of formononetin. The inhibitory effect of formononetin on proliferation of prostate cancer cells was determined using MTT assays and flow cytometry. Next, formononetin-induced alterations in cyclin D1, CDK4 and Akt expression in PC-3 cells were detected by real-time PCR and western blot. Formononetin dose-dependently inhibited prostate cancer cell proliferation via the induction of cell cycle arrest at G0/G1 phase in vitro, which was more evident in PC-3 cells. Meanwhile, concomitant with reduced phosphorylation of Akt in PC-3 cells, formononetin remarkably downregulated expression levels of cyclin D1 and CDK4 in a dose-dependent manner. More interestingly, in the in vivo studies, formononetin showed a noticeable inhibition of tumor growth in recipient mice. Formononetin could exhibit inhibitory activity against human prostate cancer cells in vivo and in vitro, which is associated with G1 cell cycle arrest by inactivation of Akt/cyclin D1/CDK4. Therefore, formononetin may be used as a candidate agent for clinical treatment of prostate cancer in the future.


Cell-cooling in flow cytometry by Peltier elements.
We have built a cooling device for cell suspensions in flow cytometry that makes use of the Peltier effect (Barnard RD, Thermo electricity in Metals and Alloys, Taylor and Francis, London; Siemens-Z 34:383-88, 1963). The prototype described here is used for cooling collection tubes during long-duration cell sorting and is capable of maintaining a temperature of 2-5 degrees C in a cell suspension of up to 3 ml. In general, Peltier element-based cooling is useful for equilibrating the temperature of small volumes of fluids. Furthermore, Peltier element-based cooling devices are easy to build and handle.


Thermodynamic-based retention time predictions of endogenous steroids in comprehensive two-dimensional gas chromatography.
This work evaluates the application of a thermodynamic model to comprehensive two-dimensional gas chromatography (GC × GC) coupled with time-of-flight mass spectrometry for anabolic agent investigation. Doping control deals with hundreds of drugs that are prohibited in sports. Drug discovery in biological matrices is a challenging task that requires powerful tools when one is faced with the rapidly changing designer drug landscape. In this work, a thermodynamic model developed for the prediction of both primary and secondary retention times in GC × GC has been applied to trimethylsilylated hydroxyl (O-TMS)- and methoxime-trimethylsilylated carbonyl (MO-TMS)-derivatized endogenous steroids. This model was previously demonstrated on a pneumatically modulated GC × GC system, and is applied for the first time to a thermally modulated GC × GC system. Preliminary one-dimensional experiments allowed the calculation of thermodynamic parameters (ΔH, ΔS, and ΔC p ) which were successfully applied for the prediction of the analytes' interactions with the stationary phases of both the first-dimension column and the second-dimension column. The model was able to predict both first-dimension and second-dimension retention times with high accuracy compared with the GC × GC experimental measurements. Maximum differences of -8.22 s in the first dimension and 0.4 s in the second dimension were encountered for the O-TMS derivatives of 11β-hydroxyandrosterone and 11-ketoetiocholanolone, respectively. For the MO-TMS derivatives, the largest discrepancies were from testosterone (9.65 ) for the first-dimension retention times and 11-keto-etiocholanolone (0.4 s) for the second-dimension retention times.


Enhancing fluoride removal from wastewater using Al/Y amended sludge biochar.
This study explored the potential of utilizing aluminum and yttrium amended (Al/Y amended) sewage sludge biochar (Al/Y-CSBC) for efficient fluoride removal from wastewater. The adsorption kinetics of fluoride on bimetallic modified Al/Y-CSBC followed the pseudo-second-order model, while the adsorption isotherm conformed to the Freundlich equation. Remarkably, the material exhibited excellent fluoride removal performance over a wide pH range, achieving a maximum adsorption capacity of 62.44 mg·g-1. Moreover, Al/Y-CSBC demonstrated exceptional reusability, maintaining 95% removal efficiency even after six regeneration cycles. The fluoride adsorption mechanism involved ion exchange, surface complexation, and electrostatic adsorption interactions. The activation and modification processes significantly increased the specific surface area of Al/Y-CSBC, leading to a high isoelectric point (pHpzc = 9.14). The incorporation of aluminum and yttrium metals exhibited a novel approach, enhancing the adsorption capacity for fluoride ions due to their strong affinity. Furthermore, the dispersing effect of biochar played a crucial role in improving defluoridation efficiency by enhancing accessibility to active sites. These findings substantiate the significant potential of Al/Y-CSBC for enhanced fluoride removal from wastewater.


Myocarditis.
Myocarditis is an uncommon, potentially life-threatening disease that presents with a wide range of symptoms in children and adults. Viral infection is the most common cause of myocarditis in developed countries, but other etiologies include bacterial and protozoal infections, toxins, drug reactions, autoimmune diseases, giant cell myocarditis, and sarcoidosis. Acute injury leads to myocyte damage, which in turn activates the innate and humeral immune system, leading to severe inflammation. In most patients, the immune reaction is eventually down-regulated and the myocardium recovers. In select cases, however, persistent myocardial inflammation leads to ongoing myocyte damage and relentless symptomatic heart failure or even death. The diagnosis is usually made based on clinical presentation and noninvasive imaging findings. Most patients respond well to standard heart failure therapy, although in severe cases, mechanical circulatory support or heart transplantation is indicated. Prognosis in acute myocarditis is generally good except in patients with giant cell myocarditis. Persistent, chronic myocarditis usually has a progressive course but may respond to immunosuppression.


The road to green innovation in agriculture: the impact of green agriculture demonstration zone on corporate green innovation.
Agricultural green transformation is crucial for addressing environmental issues like pollution and soil degradation. However, limited attention has been given to its determinants in the existing literature. This study extends the "Porter hypothesis" in agricultural economics and discusses the institutional factors influencing green transformation in Chinese agricultural enterprises from the perspective of environmental regulations. Using data from 2007 to 2020, we examine the impact of the green agriculture demonstration zone (GADZ) policy on green innovation in Chinese A-share listed agribusinesses. The results show that the policy significantly improves green innovation, leading to a 9.9% increase in patent applications. We also find that the GADZ promotes green innovation in agricultural businesses through two economic mechanisms, reducing financial risks and enhancing media attention. In addition, the policy's effect is influenced by property rights, information disclosure quality, and financial resources. Our findings offer valuable insights for promoting green innovation and high-quality agricultural development in emerging economies.


Eco-evolutionary processes underlying early warning signals of population declines.
Environmental change can impact the stability of ecological systems and cause rapid declines in populations. Abundance-based early warning signals have been shown to precede such declines, but detection prior to wild population collapses has had limited success, leading to the development of warning signals based on shifts in distribution of fitness-related traits such as body size. The dynamics of population abundances and traits in response to external environmental perturbations are controlled by a range of underlying factors such as reproductive rate, genetic variation and plasticity. However, it remains unknown how such ecological and evolutionary factors affect the stability landscape of populations and the detectability of abundance and trait-based early warning signals. Here, we apply a trait-based demographic approach and investigate both trait and population dynamics in response to gradual and increasing changes in the environment. We explore a range of ecological and evolutionary constraints under which stability of a population may be affected. We show both analytically and with simulations that strength of abundance- and trait-based warning signals are affected by ecological and evolutionary factors. Finally, we show that combining trait- and abundance-based information improves our ability to predict population declines. Our study suggests that the inclusion of trait dynamic information alongside generic warning signals should provide more accurate forecasts of the future state of biological systems.


Large scale combustion synthesis of single-walled carbon nanotubes and their characterization.
Since its invention in 1991, premixed combustion synthesis of fullerenic materials has been established as the major industrial process for manufacturing of these materials. Large-scale production of fullerenes such as C60, C70 and C84 has been implemented. More recently, combustion technology has been extended to the targeted synthesis of single-walled carbon nanotubes (SWCNT). Addition of catalyst precursor and operation at well-controlled fuel-rich but non-sooting conditions are required. Extensive parametric studies have allowed for the optimization of the formation of high-quality SWCNT. Purification techniques previously reported in the literature have been adjusted and used successfully for the nearly complete removal of metal and metal oxide. Material has been characterized using Raman spectroscopy, scanning (SEM) and transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Correlations between process conditions and nanotube properties such as length have been established. Product reproducibility and process scalability of the combustion process have been demonstrated. Sample preparation was found to affect significantly the apparent characteristics of nanotubes as seen in electron microscopy images.


Plate-Based Assays for the Characterization of Mitochondrial and Cellular Phenotypes.
The mitochondria are essential to eukaryotic life, acting as key drivers of energy generation while also being involved in the regulation of many cellular processes including apoptosis, cell proliferation, calcium homeostasis, and metabolism. Mitochondrial diseases which disrupt these processes lead to a diverse range of pathologies and lack consistency in symptom presentation. In disease, mitochondrial activity and energy homeostasis can be adapted to cellular requirements, and studies using Dictyostelium and human lymphoblastoid cell lines have shown that such changes can be facilitated by the key cellular and energy regulators, TORC1 and AMPK. Fluorescence-based assays are increasingly utilized to measure mitochondrial and cell signalling function in mitochondrial disease research. Here, we describe a streamlined method for the simultaneous measurement of mitochondrial mass, membrane potential, and reactive oxygen species production using MitoTracker Green™ FM, MitoTracker Red™ CMXRos, and DCFH-DA probes. This protocol has been adapted for both Dictyostelium and human lymphoblastoid cell lines. We also describe a method for assessing TORC1 and AMPK activity simultaneously in lymphoblastoid cells. These techniques allow for the characterization of mitochondrial defects in a rapid and easy to implement manner.


The habituation of event-related potentials to speech sounds and tones.
We examined the short- and long-term habituation of auditory event-related potentials (ERPs) elicited by tones, complex tones and digitized speech sounds (vowels and consonant-vowel-consonant syllables). Twelve different stimuli equated in loudness and duration (300 msec) were studied. To examine short-term habituation stimuli were presented in trains of 6 with interstimulus intervals of 0.5 or 1.0 sec. The first 4 stimuli in a train were identical standards. On 50% of the trains the standard in the 5th position was replaced by a deviant probe stimulus, and on 20% of the trains the standard in the 6th position was replaced by a target, a truncated standard that required a speeded button press response. Short-term habituation (STH) was complete by the third stimulus in the train and resulted in amplitude decrements of 50-75% for the N1 component. STH was partially stimulus specific in that amplitudes were larger following deviant stimuli in the 5th position than following standards. STH of the N1 was more marked for speech sounds than for loudness-matched tones or complex tones at short ISI. In addition, standard and deviant stimuli that differed in phonetic structure showed more cross-habituation than did tones or complex tones that differed in frequency. This pattern of results suggests that STH is a function of the acoustic resemblance of successive stimuli. The long-term habituation (LTH) of the ERP was studied by comparing amplitudes across balanced 5.25 m stimulus blocks over the course of the experiment. Two types of LTH were observed. The N1 showed stimulus-specific LTH in that N1 amplitudes declined during the presentation of a stimulus, but returned to control levels when a different stimulus was presented in the subsequent condition. In contrast, the P3 elicited by the deviant stimuli showed non-specific LTH, being reduced across successive blocks containing different stimuli. P3s elicited by target stimuli remained stable in amplitude.