Arousal (but not valence) amplifies the impact of salience.
Previous findings indicate that negative arousal enhances bottom-up attention biases favouring perceptual salient stimuli over less salient stimuli. The current study tests whether those effects were driven by emotional arousal or by negative valence by comparing how well participants could identify visually presented letters after hearing either a negative arousing, positive arousing or neutral sound. On each trial, some letters were presented in a high contrast font and some in a low contrast font, creating a set of targets that differed in perceptual salience. Sounds rated as more emotionally arousing led to more identification of highly salient letters but not of less salient letters, whereas sounds' valence ratings did not impact salience biases. Thus, arousal, rather than valence, is a key factor enhancing visual processing of perceptually salient targets.


Cyanotetrazolylborohydride (CTB) anion-based ionic liquids with low viscosity and high energy capacity as ultrafast-igniting hypergolic fuels.
A series of hypergolic cyanotetrazolylborohydride (CTB) anion-based ionic liquids have been synthesized by a straightforward N-hydroboration of tetrazole followed by a salt metathesis reaction, which exhibited remarkably low viscosity (<20 mPa s), high density (often >1.1 g cm-3), and ultra-short ignition delay time (as short as 1.4 ms) upon contact with white fuming nitric acid (WFNA).


Quadriceps muscle weakness influences the gait pattern in women with knee osteoarthritis.
Osteoarthritis is the most prevalent rheumatic disease in the population and is characterized by limitation of main functional activities of daily living, as the gait. Muscle strength is a variable that may be related to performance in daily tasks.Therefore, we to analyze the gait pattern in individuals with knee osteoarthritis (KOA) and to determine associations of gait variables with the level of muscle strength of knee extensors. Sixty-seven female volunteers divided into 2 groups, a KOA group (KOAG, n = 36, 66.69 ± 7.69 years) and control (n = 31, 63.68 ± 6.97 years), participated in the study. The volunteers walked on a 10-m platform at their usual gait speed, using 2 pressure sensors positioned at the base of the hallux and calcaneus. The mean step time, support and double support times, swing time and gait speed were calculated. The evaluation of the quadriceps isometric torque was performed in an extensor chair, with hip and knee flexion at 90°. The procedure consisted of three maximal contractions of knee extension. Peak torque was determined by the highest torque value obtained after the onset of muscle contraction. For statistical analysis, one-way ANOVA and Pearson's correlation were used, with p < 0.05. The KOAG had a 54.76% longer support time, a 13% longer step time (p < 0.001), a 30% decrease in swing time (p < 0.001) and a 10.7% decrease in gait speed (p = 0.001) compared with controls. The quadriceps isometric torque was 34% (p = 0.001) lower in the KOAG. There was a correlation between kinematic variables and quadriceps torque. Weakness of the quadriceps muscle in women with KOA influences gait pattern, resulting in reduced speed associated with a shorter swing time and longer support time.


Two invasive herbivores on a shared host: patterns and consequences of phytohormone induction.
Herbivore-induced changes in host quality mediate indirect interactions between herbivores. The nature of these indirect interactions can vary depending on the identity of herbivores involved, species-specific induction of defense-signaling pathways, and sequence of attack. However, our understanding of the role of these signaling pathways in the success of multiple exotic herbivores is less known. Eastern hemlock (Tsuga canadensis) is attacked by two invasive herbivores [elongate hemlock scale (EHS; Fiorinia externa) and hemlock woolly adelgid (HWA; Adelges tsugae)] throughout much of its range, but prior attack by EHS is known to deter HWA. The potential role of phytohormones in this interaction is poorly understood. We measured endogenous levels of phytohormones in eastern hemlock in response to attack by these invasive herbivores. We also used exogenous application of methyl jasmonate (MJ) and acibenzolar-S-methyl (ASM), a salicylic acid (SA) pathway elicitor, to test the hypothesis that defense-signaling phytohormones typically induced by herbivores could deter HWA. Resistance to adelgid attack was assessed using a behavioral assay. Adelgid feeding significantly elevated both abscisic acid (ABA) and SA in local tissues, while EHS feeding had no detectable effect on either phytohormone. HWA progrediens and sistens crawlers preferred to settle on ASM-treated foliage. In contrast, HWA crawlers actively avoided settlement on MJ-treated foliage. We suggest that induction of ABA- and SA-signaling pathways, in concert with defense-signaling interference, may aid HWA invasion success, and that defense-signaling interference, induced by exotic competitors, may mediate resistance of native hosts.


Morphology of Helicobacter pylori as a result of peptidoglycan and cytoskeleton rearrangements.
Helicobacter pylori is a Gram-negative, microaerophilic bacterium colonising the gastric mucosa. Normally, this bacterium has a spiral shape, which is crucial for proper colonisation of the stomach and cork-screwing penetration of dense mucin covering this organ. However, H. pylori may also form curved/straight rods, filamentous forms and coccoid forms. This morphological variability affects nutrient transport and respiration processes, as well as motility, the ability to form aggregates/biofilms, and resistance to adverse environmental factors. For this reason, a more accurate understanding of the molecular determinants that control the morphology of H. pylori seems to be crucial in increasing the effectiveness of antibacterial therapies directed against this microorganism. This article focuses on the molecular factors responsible for peptidoglycan and cytoskeleton rearrangements affecting H. pylori morphology and survivability. In addition, the existence of proteins associated with modifications of H. pylori morphology as potential targets in therapies reducing the virulence of this bacterium has been suggested.


[The significance of determination of urinary type IV collagen concentrations from a random urine collection in patients with non-insulin dependent diabetes mellitus].
Recently, we have developed a highly sensitive assay system for quantitative measurement of urinary type IV collagen. To obtain a basic evaluation of the assay system we used urine specimens, collected randomly and studied the relation to diabetic nephropathy in patients with non-insulin dependent diabetes mellitus (NIDDM). It was shown that this assay system could measure the samples without concentrating the urine. Urinary sediments which were reported to interfere with the assay could be removed by adding Tris-buffer. In the clinical studies, urinary type IV collagen concentrations were significantly higher in patients with NIDDM regardless of the presence or the absence of albumin. Cases with abnormal values of urinary type IV collagen in the normal albuminuria group were 41.6%, while those with abnormal values of urinary transferrin excretion were 31.0%. Furthermore, among the normal albuminuria group, glycosylated hemoglobin (HbA1c) levels were higher in the groups of abnormal values of urinary type IV collagen than those within the reference values. These results obtained herein suggest that urinary type IV collagen could be a useful marker for the early stage of diabetic nephropathy.


Development of a method for recycling of CRT funnel glass.
Finding better solutions to manage and recycle cathode-ray tube (CRT) glass is crucial for reducing the environmental threats due to the disposal of the glass. In this paper, the results of a laboratory study on developing a method for removing lead from crushed funnel glass surface and re-utilizing the treated glass in cement mortar are presented. The results demonstrate that nitric acid at 3-5% concentration levels can be used to remove most of the lead from the crushed funnel glass surface and render it as non-hazardous waste based on toxicity characteristics leaching procedure (TCLP) testing. It is noted that the particle size of glass and number of treatment cycles are significant factors affecting lead extraction. The study further demonstrated that it is feasible to utilize up to 100% of treated funnel glass as a replacement for natural sand for producing cement mortar.


[Arteriovenous fistulas for hemodialysis--patency rates and complications--a retrospective study].
In this study we investigated 213 forearm-fistulas, 233 elbow-fistulas, 21 bridge-fistulas and 3 axillo-axillary vascular accesses. 129 revisions were necessary to preserve the vascular access. The patency rates of the 170 primary forearm fistulas and the 140 primary elbow fistulas were 45 resp. 54%. We preferred the end-to-end-anastomosis for the forearm position and for the elbow the side-to-end-anastomosis. There were no differences between the type of anastomosis, localization and the second constructions as regards the patency rates. The results of the-end-to-end-fistulas were much better in male than female patients. Besides we had better results after thrombectomy in the elbow position compared to the forearm position. We found that a vein diameter less than 2 mm gave worse results. The most frequent complication of the fistulas was the thrombosis. Autologous and alloplastic transplants (grafts) were only taken if it wasn't possible to create an arteriovenous fistula by the orthotopic vessels.


Modelling the within-host dynamics of the foot-and-mouth disease virus in cattle.
In this paper we investigate the within-host dynamics of the foot-and-mouth disease virus (FMDV) in cattle using previously published data for 8 experimentally infected cows. An 8-compartment, 14-parameter differential equation model was fitted to data collected from each cow every 24 h over the course of an infection on: (i) the concentration of FMDV genomes in the blood, (ii) the concentration of infectious virus in the blood, (iii) antibody levels, and (iv) interferon levels. Model parameters were estimated using maximum-likelihood methods. The likelihood surface was sampled using Markov chain Monte Carlo methods giving credible intervals for each of the model parameters. The model was able to capture the within-host dynamics well for 6 of the infections, with both the innate (type 1 interferon) and antibody responses playing key roles in determining the height and duration of peak levels of virus. There was considerable variation between virus dynamics in individual cattle which was only partly accounted for by inferred differences in the dose of virus received. A better understanding of the within-host dynamics also provides insights into the dynamics of infectiousness and the transmission of virus to new hosts.


Investigation of the ASR family in foxtail millet and the role of ASR1 in drought/oxidative stress tolerance.
Six foxtail millet ASR genes were regulated by various stress-related signals. Overexpression of ASR1 increased drought and oxidative tolerance by controlling ROS homeostasis and regulating oxidation-related genes in tobacco plants. Abscisic acid stress ripening (ASR) proteins with ABA/WDS domains constituted a class of plant-specific transcription factors, playing important roles in plant development, growth and abiotic stress responses. However, only a few ASRs genes have been characterized in crop plants and none was reported so far in foxtail millet (Setaria italic), an important drought-tolerant crop and model bioenergy grain crop. In the present study, we identified six foxtail millet ASR genes. Gene structure, protein alignments and phylogenetic relationships were analyzed. Transcript expression patterns of ASR genes revealed that ASRs might play important roles in stress-related signaling and abiotic stress responses in diverse tissues in foxtail millet. Subcellular localization assays showed that SiASR1 localized in the nucleus. Overexpression of SiASR1 in tobacco remarkably increased tolerance to drought and oxidative stresses, as determined through developmental and physiological analyses of germination rate, root growth, survival rate, relative water content, ion leakage, chlorophyll content and antioxidant enzyme activities. Furthermore, expression of SiASR1 modulated the transcript levels of oxidation-related genes, including NtSOD, NtAPX, NtCAT, NtRbohA and NtRbohB, under drought and oxidative stress conditions. These results provide a foundation for evolutionary and functional characterization of the ASR gene family in foxtail millet.


Is a minimally invasive approach for resection of benign cardiac masses superior to standard full sternotomy?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'is a minimally invasive approach for resection of benign cardiac masses superior to standard full sternotomy?' A total of 50 papers were found using the reported search, of which, 11 represented the best evidence to answer the clinical question. The authors, country, journal, date of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. All 11 papers were retrospective studies, from which 4 were case-control studies comparing the minimally invasive approach with conventional full sternotomy, and 7 were case series. There were two minimally invasive techniques used, a right mini-thoracotomy and a partial hemi-sternotomy, the former being the most commonly used. The resection of benign cardiac masses is a low-risk procedure, with no mortality or conversions to full sternotomy reported. From the 4 case-control studies, cross-clamp time was similar in both groups, and only one report found a prolonged perfusion time with the minimally invasive approach. The incidence of major postoperative complications, including bleeding requiring reoperation (average from case-control studies: 0-4.5 vs 0-5.8%), renal failure (0 vs 0-10%) and prolonged ventilation (6-13 vs 11-19%), for the two approaches was similar. The incidence of postoperative stroke was better for the minimally invasive approach in one study (0 vs 14%, P = 0.023). The main advantages of this technique are shorter intensive care unit (26-31 vs 46-60 h) and hospital stay (3.6-5.2 vs 6.2-7.4 days), the minimally invasive approach being significantly better in one and three reports, respectively. We conclude that minimally invasive resection of a benign cardiac mass using a right mini-thoracotomy approach can be performed with an operative morbidity and mortality at least similar to the standard full sternotomy approach. The information currently available for the minimally invasive approach for the resection of benign cardiac masses is limited and based only on retrospective studies and, therefore, prospective studies are required to confirm the potential benefits of minimally invasive surgery.


Zoonotic mosquito-borne arboviruses: Spillover, spillback, and realistic mitigation strategies.
Emerging zoonotic mosquito-borne viruses pose increasing health threats because of growing mosquito population, geographic expansions, and control challenges. We emphasize the need for global preparedness to effectively mitigate the health, societal, and economic impacts of spillover by these viruses through proactive measures of prediction, surveillance, prevention, and treatment.


In Situ Engineering of Inorganic-Rich Solid Electrolyte Interphases via Anion Choice Enables Stable, Lithium Anodes.
The discovery of liquid battery electrolytes that facilitate the formation of stable solid electrolyte interphases (SEIs) to mitigate dendrite formation is imperative to enable lithium anodes in next-generation energy-dense batteries. Compared to traditional electrolyte solvents, tetrahydrofuran (THF)-based electrolyte systems have demonstrated great success in enabling high-stability lithium anodes by encouraging the decomposition of anions (instead of organic solvent) and thus generating inorganic-rich SEIs. Herein, by employing a variety of different lithium salts (i.e., LiPF6, LiTFSI, LiFSI, and LiDFOB), we demonstrate that electrolyte anions modulate the inorganic composition and resulting properties of the SEI. Through novel analytical ToF-SIMS methods, such as hierarchical clustering of depth profiles and compositional analysis using integrated yields, we examine the chemical composition and morphology of the SEIs generated from each electrolyte system. Notably, the LiDFOB electrolyte provides an exceptionally stable system to enable lithium anodes, delivering > 1500 cycles at a current density of 0.5 mAh g-1 and a capacity of 0.5 mAh g-1 in symmetrical cells. Furthermore, Li//LFP cells using this electrolyte demonstrate high-rate, reversible lithium storage, supplying 139 mAh g(LFP) -1 at C/2 (∼ 0.991 mAh cm-2 , @ 0.61 mA cm-2 ) with 87.5% capacity retention over 300 cycles (average Coulombic efficiency >99.86%). This article is protected by copyright. All rights reserved.


Poisoning in the United States: 2012 emergency medicine report of the National Poison Data System.
Deaths from drug overdose have become the leading cause of injury death in the United States, where the poison center system is available to provide real-time advice and collect data about a variety of poisonings. In 2012, emergency medical providers were confronted with new poisonings, such as bath salts (substituted cathinones) and Spice (synthetic cannabinoid drugs), as well as continued trends in established poisonings such as from prescription opioids. This article addresses current trends in opioid poisonings; new substances implicated in poisoning cases, including unit-dose laundry detergents, bath salts, Spice, and energy drinks; and the role of poison centers in public health emergencies such as the Fukushima radiation incident.


Radon as a risk factor of lung cancer
Radon is the second leading cause of lung cancer after smoking. Indoor radon concentration poses a significant and potentially subject to the prevention risk factor of lung cancer development. The paper present the history of studies assessing occupational and indoor radon exposure and an impact of international organizations for raise public and political awareness about the consequences of long term exposure to residential radon, resulting in the European Directive 2013/59/Euratom of 5 December 2013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation.


Two novel Ln8 clusters bridged by CO32- effectively convert CO2 into oxazolidinones and cyclic carbonates.
It is difficult and challenging to design and construct high-nuclearity Ln(III)-based clusters due to the high coordination numbers and versatile coordination geometries of Ln(III) ions. Herein, two novel octanuclear Ln(III)-based clusters [Ln8(H2L-)4(HL2-)4(NO3)6 (CO3)2](NO3)2·2CH3CN (Ln = Nd (1) and Sm (2)) have been synthesized under solvothermal conditions. The X-ray single analysis reveals that both 1 and 2 are octanuclear structures and the eight central Ln(III) ions are bridged by two CO32- anions. Catalytic study revealed that 1 and 2 can effectively catalyze the cycloaddition reaction of CO2 and aziridines or epoxides simultaneously under mild conditions. What is more, cluster 1, as a heterogeneous catalyst, can be reused at least three times without obvious loss in catalytic activity for coupling of CO2 and epoxides. To our knowledge, cluster 1 is the first Ln(III)-based cluster catalyst used for the conversion of CO2 with aziridines or epoxides simultaneously. This work provides a successful strategy to integrate high-nuclear Ln(III)-based clusters for CO2 conversion, which may open a new space for the construction of multifunctional high-nuclear Ln(III)-based clusters as efficient catalysts for CO2 conversion.


Elongation of the developing spinal cord is driven by Oct4-type transcription factor-mediated regulation of retinoic acid signaling in zebrafish embryos.
Elongation of the spinal cord is dependent on neural development from neuromesodermal progenitors in the tail bud. We previously showed the involvement of the Oct4-type gene, pou5f3, in this process in zebrafish mainly by dominant-interference gene induction, but, to compensate for the limitation of this transgene approach, mutant analysis was indispensable. pou5f3 involvement in the signaling pathways was another unsolved question. We examined the phenotypes of pou5f3 mutants and the effects of Pou5f3 activation by the tamoxifen-ERT2 system in the posterior neural tube, together confirming the involvement of pou5f3. The reporter assays using P19 cells implicated tail bud-related transcription factors in pou5f3 expression. Regulation of tail bud development by retinoic acid (RA) signaling was confirmed by treatment of embryos with RA and the synthesis inhibitor, and in vitro reporter assays further showed that RA signaling regulated pou5f3 expression. Importantly, the expression of the RA degradation enzyme gene, cyp26a1, was down-regulated in embryos with disrupted pou5f3 activity. The involvement of pou5f3 in spinal cord extension was supported by using mutants and the gain-of-function approach. Our findings further suggest that pou5f3 regulates the RA level, contributing to neurogenesis in the posterior neural tube.


A clinical trial of a novel emulsion for potential use as a saliva substitute in patients with radiation-induced xerostomia.
Researchers have recently developed a novel oily formulation for potential use as a saliva substitute for the treatment of dry mouth. The aim of this randomised, crossover study was to compare this new formulation to a currently available saliva substitute and a control of water on measures of mastication, subjective feeling of oral dryness and product acceptability. Forty participants treated with radiotherapy to the head and neck and experiencing xerostomia were invited to participate in the trial. Each participant trialled all three products in a randomised order. The effect of each product was measured using the Test of Masticating and Swallowing Solids (TOMASS), the Shortened Xerostomia Inventory (SXI) and a questionnaire designed to test patient acceptability of each product. Outcome data were gathered in a single session after the first administration of each product to evaluate immediate effects and after 7 days of use to evaluate longer-term effects. Statistical analyses consisted of repeated-measures analysis of variance and mixed models. There was no evidence that application of the three formulations had an effect on any of the TOMASS measures, either immediately or after one week of use (P > 0·05). There was a significant main effect of formulation on the SXI score (P = 0·02). Application of the novel emulsion resulted in a clinically small but significant improvement in SXI score (P < 0·01); however, application of methylcellulose (P = 0·21) and water (P = 0·81) resulted in no significant difference. There was no difference in participant acceptability between the three products (P = 0·32). The novel oily emulsion showed no clinically significant benefit over two existing products for relief of xerostomia. Indeed, none of the three products demonstrated significant change in patient outcomes.


Modelling the contribution of changes in family life to time trends in adolescent conduct problems.
The past half-century has seen significant changes in family life, including an increase in parental divorce, increases in the numbers of lone parent and stepfamilies, changes in socioeconomic well being, and a decrease in family size. Evidence also shows substantial time trends in adolescent mental health, including a marked increase in conduct problems over the last 25 years of the 20th Century in the UK. The aim of this study was to examine how these two sets of trends may be related. To illustrate the complexity of the issues involved, we focused on three well-established family risks for conduct problems: family type, income and family size. Three community samples of adolescents from England, Scotland and Wales were compared: 10,348 16-year olds assessed in 1974 as part of the National Child Development Study, 7234 16-year olds assessed in 1986 as part of the British Cohort Study, and 860 15-year olds assessed in the 1999 British Child and Adolescent Mental Health Survey. Parents completed comparable ratings of conduct problems in each survey and provided information on family type, income and size. Findings highlight important variations in both the prevalence of these family variables and their associations with conduct problems over time, underscoring the complex conceptual issues involved in testing causes of trends in mental health.


The Role of Cannabis within an Emerging Perspective on Schizophrenia.
Background: Approximately 0.5% of the population is diagnosed with some form of schizophrenia, under the prevailing view that the pathology is best treated using pharmaceutical medications that act on monoamine receptors. Methods: We briefly review evidence on the impact of environmental forces, particularly the effect of autoimmune activity, in the expression of schizophrenic profiles and the role of Cannabis therapy for regulating immunological functioning. Results: A review of the literature shows that phytocannabinoid consumption may be a safe and effective treatment option for schizophrenia as a primary or adjunctive therapy. Conclusions: Emerging research suggests that Cannabis can be used as a treatment for schizophrenia within a broader etiological perspective that focuses on environmental, autoimmune, and neuroinflammatory causes of the disorder, offering a fresh start and newfound hope for those suffering from this debilitating and poorly understood disease.


Substituent effects of porphyrins on structures and photophysical properties of amphiphilic porphyrin aggregates.
Substituent effects of porphyrin on the structures and photophysical properties of the J-aggregates of protonated 5-(4-alkoxyphenyl)-10,15,20-tris(4-sulfonatophenyl)porphyrin have been examined for the first time. Selective formation of the porphyrin J-aggregate was attained when suitable length of the alkoxy group was employed for the amphiphilic porphyrin. Namely, a regular leaflike structure was observed for the J-aggregates of protonated 5-(4-octyloxyphenyl)-10,15,20-tris(4-sulfonatophenyl)porphyrin, which was consistent with the results obtained by using the UV-visible absorption and dynamic light-scattering measurements. A bilayer structure in which the hydrophobic alkoxyl groups facing inside the bilayer are interdigitated to each other, whereas the hydrophilic porphyrin moieties are exposed outside, was proposed to explain the unique porphyrin J-aggregate. Fast energy migration and efficient quenching by defect site in the J-aggregates were suggested to rationalize the short lifetimes of the excited J-aggregates.


Influence of age on the transparency of the lens in normals: a population study with help of the Lens Opacity Meter 701.
The Lens Opacity Meter 701 measures the lens density quantifying the back light scatter of the lens. The instrument emits a modulated dark-red beam which runs along the optic axis of the lens. The stray light is converted into an electrical impulse which is displayed and printed using a numerical scale. The lens density in a normal population was investigated with this instrument in order to study the influence of age on the opacification process.


Intermittent hypoxia improves endurance performance and submaximal exercise efficiency.
The purpose of the present study was to elucidate the influence of intermittent hypobaric hypoxia at rest on endurance performance and cardiorespiratory and hematological adaptations in trained endurance athletes. Twelve trained male endurance runners were assigned to either a hypoxic group (n = 6) or a control group (n = 6). The subjects in the hypoxic group were exposed to a simulated altitude of 4500 m for 90 min, three times a week for 3 weeks. The measurements of 3000 m running time, running time to exhaustion, and cardiorespiratory parameters during maximal exercise test and resting hematological status were performed before (Pre) and after 3 weeks of intermittent hypoxic exposure (Post). These measurements were repeated after the cessation of intermittent hypoxia for 3 weeks (Re). In the control group, the same parameters were determined at Pre, Post, and Re for the subjects not exposed to intermittent hypoxia. The athletes in both groups continued their normal training together at sea level throughout the experiment. In the hypoxic group, the 3000 m running time and running time to exhaustion during maximal exercise test improved. Neither cardiorespiratory parameters to maximal exercise nor resting hematological parameters were changed in either group at Post, whereas oxygen uptake (.V(O2)) during submaximal exercise decreased significantly in the hypoxic group. After cessation of intermittent hypoxia for 3 weeks, the improved 3000 m running time and running time to exhaustion tended to decline, and the decreased .V(O2) during submaximal exercise returned to Pre level. These results suggest that intermittent hypoxia at rest could improve endurance performance and submaximal exercise efficiency at sea level in trained endurance athletes, but these improvements are not maintained after the cessation of intermittent hypoxia for 3 weeks.


Design of a cost-effective, hemodynamically adjustable model for resuscitative endovascular balloon occlusion of the aorta (REBOA) simulation.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct technique for salvaging patients with noncompressible torso hemorrhage. Current REBOA training paradigms require large animals, virtual reality simulators, or human cadavers for acquisition of skills. These training strategies are expensive and resource intensive, which may prevent widespread dissemination of REBOA. We have developed a low-cost, near-physiologic, pulsatile REBOA simulator by connecting an anatomic vascular circuit constructed out of latex and polyvinyl chloride tubing to a commercially available pump. This pulsatile simulator is capable of generating cardiac outputs ranging from 1.7 to 6.8 L/min with corresponding arterial blood pressures of 54 to 226/14 to 121 mmHg. The simulator accommodates a 12 French introducer sheath and a CODA balloon catheter. Upon balloon inflation, the arterial waveform distal to the occlusion flattens, distal pulsation within the simulator is lost, and systolic blood pressures proximal to the balloon catheter increase by up to 62 mmHg. Further development and validation of this simulator will allow for refinement, reduction, and replacement of large animal models, costly virtual reality simulators, and perfused cadavers for training purposes. This will ultimately facilitate the low-cost, high-fidelity REBOA simulation needed for the widespread dissemination of this life-saving technique.


Lithothamnion muelleri controls inflammatory responses, target organ injury and lethality associated with graft-versus-host disease in mice.
Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft-versus-host disease (GVHD), using a model of adoptive splenocyte transfer from C57BL/6 donors into B6D2F1 recipient mice. Mice treated with LM showed reduced clinical signs of disease and mortality when compared with untreated mice. LM-treated mice had reduced tissue injury, less bacterial translocation, and decreased levels of proinflammatory cytokines and chemokines (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5)). The polysaccharide-rich fraction derived from LM could inhibit leukocyte rolling and adhesion in intestinal venules, as assessed by intravital microscopy. LM treatment did not impair the beneficial effects of graft-versus-leukaemia (GVL). Altogether, our studies suggest that treatment with Lithothamnion muelleri has a potential therapeutic application in GVHD treatment.


Transcriptional regulation of the human reduced folate carrier A1/A2 promoter: Identification of critical roles for the USF and GATA families of transcription factors.
The human reduced folate carrier (hRFC) gene has a complex regulation involving 6 alternatively spliced non-coding exons and promoters (A1/A2, A, B, C, D, and E). The hRFC-A1/A2 promoter is unique in that it transcribes a novel transcript with an in-frame AUG in non-coding exon A1/A2 that encodes a modified hRFC protein with altered transport function. In this report, we characterize the hRFC-A1/A2 promoter in HepG2 human hepatoma cells. By transfecting HepG2 cells with 5' and 3' deletion constructs, a transcriptionally important 270 bp region was identified. Gel shift assays identified transcription factor binding to three E-box elements and one GATA site within this region. These elements were verified by transfections of mutant constructs into HepG2 cells. Cotransfections in Drosophila Mel-2 cells confirmed promoter activation by USF1 and GATA1. A physical association between USF1 and GATA1 was demonstrated by their co-immunoprecipitation. By real time PCR analysis of transfected HepG2 cells, USF1 and GATA1 increased endogenous hRFC-A1/A2 transcripts. Altogether, our results demonstrate a transcriptionally important region in the hRFC-A1/A2 promoter including E-box and GATA elements, and a transactivation by USF1 and GATA1 proteins. Our results further establish the complexity of hRFC regulation, as a means of ensuring adequate folate cofactor transport for cell proliferation.


Differences in mitral valve geometry between atrial and ventricular functional mitral regurgitation in patients with atrial fibrillation: a 3D transoesophageal echocardiography study.
This study investigated geometric differences in mitral valve apparatus between atrial functional mitral regurgitation (A-FMR) and functional mitral regurgitation (FMR) with left ventricular (LV) dysfunction in patients with atrial fibrillation (AF) using 3D transoesophageal echocardiography (TOE). In total, 135 moderate or greater FMR patients with persistent AF or atrial flutter underwent 3D TOE. Fifty-six patients had A-FMR, defined as preserved LV ejection fraction (LVEF) of ≥50% and normal LV wall motion. Seventy-nine patients had ventricular FMR (V-FMR), defined as LV dysfunction (LVEF of <50%) or LV wall motion abnormality. To evaluate mitral leaflet coaptation, the coapted area was calculated as follows: total leaflet area (TLA) in end-diastole - closed leaflet area in mid-systole. Although annular area (AA) did not significantly differ between the two groups, TLA was significantly smaller in A-FMR than in V-FMR (P = 0.005). TLA/AA, indicating the degree of the leaflet remodelling, was significantly smaller in A-FMR than in V-FMR (P < 0.001). A-FMR had significantly smaller posterior mitral leaflet tethering height and angle measured at three anteroposterior planes (lateral, central, and medial) than V-FMR (all P < 0.001). However, vena contracta width (VCW) measured on long-axis view on TOE and coapted area, which correlated with VCW (r = -0.464, P < 0.001), were similar between the two groups. Mitral leaflet remodelling may be less in A-FMR compared with V-FMR. However, leaflet tethering was smaller in A-FMR than in V-FMR, and this may result in a similar degree of mitral leaflet coaptation and mitral regurgitation severity.


Multimedia clinical simulation based on patient records: authoring, user interface, pedagogy.
As an alternative to available computer-based clinical simulations that mimic patient encounters, we developed a clinical case simulation that more closely resembles the patient record. Our system, implemented in a Macintosh program called Short Rounds, features rapid and customized case authoring by editing a structured text file, a dynamic user interface that presents a case-specific screen layout, and a pedagogical model that is suitable for teaching third-year medical students. We believe this approach allows faculty members to create multimedia case simulations in shorter periods of time than in available clinical simulations.


Hand-held photometer based on liquid-core waveguide absorption detection for nanoliter-scale samples.
This paper reports a fully integrated hand-held photometer based on the liquid-core waveguide (LCW) detection principle for nanoliter-scale samples. All components of the photometer including light-emitting diode (LED) light source, LCW flow cell, photodiode detector, dropper pump, electronic circuit, liquid-crystal display screen, and battery were fully integrated into a small-sized (12 x 4.5 x 2.1 cm) instrument. A bent optical coupler was developed to conduct the detection light into or out of the LCW flow cell through its sidewall. This design allowed the sampling probe, input and output optical couplers, and LCW flow cell to be integrated in a single Teflon AF capillary, which significantly simplified system structure, improved working reliability, and reduced sample consumption. Two UV-LEDs were used as light source in the photometer to achieve dual wavelength detection at 260 and 280 nm, which was applied to assess on-site the quality and quantity of DNA samples. The effective optical path length of the photometer was approximately 15 mm with a sample consumption of only 350 nL. The potential of the photometer applied in point of care testing was also demonstrated in the measurement of total cholesterol in serum samples.


Reconstruction of the ossicular chain with hydroxyapatite implants.
This paper describes the clinical results of the application of dense hydroxyapatite assembly prostheses. A study of 60 patients with hydroxyapatite incus prostheses revealed an air-bone gap closure within 20 dB in 86.6% of the cases, and an air-bone gap closure of less than 10 dB in 60.6%. No improvement was seen in 5% of the patients. The follow-up period varied from 1 to 4 years with an average of 2 years, and the hearing gain remained constant during this period. Hydroxyapatite may be considered a useful material for reconstructive middle ear surgery.


Parents' perceptions of their children's mental health during COVID-19: Evidence from Canada.
This study examined several factors affecting the perception of Canadian parents about their children's mental health during COVID-19. The contribution of this research included fresh evidence from examining the demographic and sociological factors influencing children's well-being during COVID-19 using the Canadian context. We used a cross-sectional dataset from Statistics Canada titled Impacts of COVID-19 on Canadians - Parenting during the Pandemic (2020). We relied on an ordered logit model and computed the respective odds ratios. Our results showed that parents with a university degree and those working from home are less concerned about their children's mental health. Nonetheless, having a disabled child, belonging to a minority, having children aged six-to fourteen-years old, and having lost a job or experienced a drop in working hours increased parents' worry. Additionally, having worries about being connected with family and friends, being concerned about work-life balance, feeling lonely at home, and waiting for the reopening of childcare services all increased the likelihood of parents' anxiety about their child's mental health. When running the analysis by province, we saw that being an immigrant and belonging to a minority increased parents' worry only in Ontario and British Columbia. Policymakers are encouraged to foster working-from-home practices as working from home has been linked to less worry about child mental health, mainly among mothers, as indicated in our gender heterogeneity analysis. In addition, it is advised that families with a disabled child, and families belonging to a minority received additional support. Lastly, policymakers are advised to consider the social cost of preventive measures and incorporate this into any future preventative policymaking as the social impact variables were robust across all models.


Magnetic resonance imaging findings in adult-form myotonic dystrophy type 1.
The adult form of myotonic dystrophy type 1 is a neuromuscular disorder with multisystem involvement, including the central nervous system (CNS). The presenting clinical features of this condition include distal muscle weakness, myotonia, intellectual decline, cataract, frontal baldness and testicular atrophy. Magnetic resonance (MR) imaging shows characteristic white matter changes in the CNS. The clinical presentation, characteristic white matter changes in the brain on MR imaging and electromyographic findings aid in the diagnosis of this disorder.


A survey of neonatal tetanus and perinatal mortality in southern Muslim communities in Thailand.
The objective was to obtain the incidence rate of neonatal tetanus, perinatal mortality rate, and the coverage of health care utilization in the rural Muslim in the lower part of southern Thailand. In a retrospective field study, the rural populations of Narathiwat, Yala and Pattani provinces were studied by cluster sampling technique. The still birth rate and early neonatal mortality rate were 15.3 per 1,000 births and 11.2 per 1,000 live births, respectively. The maternal mortality rate was 1.7 per 1,000 live births. 55% of all pregnancies received 2 injections of tetanus toxoid, 80% of deliveries were performed by traditional birth attendants. The incidence rate of neonatal tetanus was 0.9 per 1,000 live births. The coverage of health service for prevention of perinatal mortality was low and these perinatal and maternal mortality rates were unacceptably high. In contrast, the incidence of neonatal tetanus was not particularly high for unknown reasons.


Estimation of solidification time during casting by use of a heat transfer model.
Time-dependent temperature profiles in dental casting molds were analyzed by an unsteady heat conduction model. The thermal conductivity and initial temperature of the mold greatly affected the heat transfer in the mold. The thermal conductivities of gypsum- and phosphate-bonded investments at high temperatures were accurately measured by means of the hot wire method. From the data obtained, the solidification times of Ag, Ag alloy, and Co-Cr alloy were calculated and compared with the experimental results.


Expression of the MDR1 and MRP genes in patients with lymphoma with primary bone marrow involvement.
Expression of MDR1 and MRP genes in patients with low-grade and high-grade non-Hodgkin's lymphomas with primary bone marrow involvement before and after chemotherapy was investigated. The data demonstrate that overexpression of MDR1 and MRP genes in hematological malignancies elevates in patients after chemotherapy and correlates with poor clinic prognosis and more frequent recurrences of the malignancies.


The Oregon depo-Provera program: a five-year follow-up.
In 1999, the Oregon State Legislature, concerned about the risk certain sexual offenders might pose to their communities upon release from prison, enacted House Bill 2500. This bill required selected offenders to be evaluated prior to their release to determine whether medical treatment with medroxyprogesterone acetate (MPA), also known by its trade name of depo-Provera, was indicated to reduce their risk. The present study reviewed the first 275 men to be evaluated under this program from the years 2000 through 2004. Data were collected on diagnoses and outcome on three groups: men judged to need MPA who eventually went on to actually receive it; men recommended to receive MPA who, for a variety of reasons, did not receive the medication; and men deemed not to need MPA. Outcome measures included recidivism data, including reoffenses, parole violations, and reincarcerations, and whether these were sexual in nature. Data were also collected on employment and whether supervising officers believed the men in each group were doing well. Significant differences emerged among these three groups, with men actually receiving depo-Provera committing no new sexual offenses and also committing fewer overall offenses and violations compared to the other two groups. In addition, almost one third of men judged to need medication but who did not receive it committed a new offense and almost 60% of these were sexual in nature. While generalizations from these types of retrospective and partially subjective findings are inherently limited, the present study lends credence to the belief that, in selected offenders, anti-androgenic medication can be a valuable, if time-limited, addition to a cognitive and behavioral treatment program. Suggestions for more practical and far-reaching implementation of this adjunctive approach are offered.


Unusual ampullary sperm crypts, and behavior and role of the cumulus oophorus, in the oviduct of the least shrew, Cryptotis parva.
The gametes of the least shrew, Cryptotis parva, were studied in regard to their maturation and structure, and with particular emphasis on their behavior in the fallopian tube, from the time of ovulation until the appearance of two-cell embryos beginning some 9 h after ovulation. Cryptotis spermatozoa are organized according to the conventional eutherian mold, with the exception of a barbed perforatorium and an unusual plasma membrane density lent by a bristly coat where it overlies the acrosome rim. In the epididymis they undergo a maturation of the capacity for motility and an -S-S-related stabilization of the nucleus and tail organelles, with the cauda housing only approximately 4-5 million spermatozoa. Mating involves penile locking and also the deposition of a modest vaginal plug that covers the cervix. The short (4-5 mm) fallopian tube has three regions-a simple isthmus, a relatively narrow ampulla populated throughout by ciliated crypts, and a crypt-free terminal infundibulum-the fertilization site. Unlike the situation in most mammals, the tubal isthmus was devoid of spermatozoa in mated females before and after ovulation, which occurred approximately 13 h post-hCG and produced a mean of 5.7 ova. However, the ampulla then housed approximately 1500 active cells in groups within the ciliated crypts, sometimes together with leukocytes but with few spermatozoa above in the infundibulum. Within about 1 h after their ovulation from approximately 400-microm follicles, eggs were penetrated while in the infundibulum despite the nonexpanded hyaluronidase-resistant state of the cumulus oophorus. However, on moving down to the ampulla by 2-4 h after ovulation, the dense cumulus around fertilized eggs appeared to proliferate and began to disperse coincidentally with secretion of a hyaluronidase-sensitive matrix in which hundreds of motile spermatozoa often became enmeshed. This cumulus change also occurred around unfertilized eggs, though more slowly, but not around fertilized or unfertilized eggs cultured in vitro. Thus, cumulus matrix production appeared to be stimulated to an important degree by factors in the oviduct, not by preovulatory gonadotropins as in many mammals. Although cumulus-invested eggs were fertilized readily in vitro, cumulus-free eggs of the same age were never fertilized, and spermatozoa bound to the zona pellucida had intact acrosomes. This and related evidence from other shrews makes it seem likely that the soricid cumulus has an essential role in fertilization and may induce the acrosome reaction.


[Nursing Care of Older People With Clostridium Difficile Infection].
The global incidence of Clostridium difficile infection (CDI) has increased in recent decades. The etiology of CDI includes aging as well as the misuse of antibiotics. This highly infectious disease requires that healthcare workers be vigilant and take isolation precautions, particularly in long-term facilities. CDI contributes to the development of severe diarrhea, which may cause imbalance of electrolytes, malabsorption of nutrients, physical disabilities, and psychosocial impacts in older patients. This article explores the pathophysiology, impacts, treatments (e.g., fecal microbiota transplantation [FMT]), and daily care regimens related to CDI with the goal of helping healthcare workers understand this disease and take action during the early stages of CDI.


A multidisciplinary audit of patients' seating needs.
Although emphasis in the literature may be on the use of pressure-relieving mattresses and specialist beds, seating is also an important part of preserving tissue viability. A collaborative approach within the multidisciplinary team is of value. Equipment is of limited value if not complemented by best practice, carried out by well-educated staff. Patients' views should be elicited.


Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization.
Hypoxia is a common feature of solid tumors. It is closely related to tumor progression. Exosomal microRNAs derived from cancers are considered to be mediators between cancer cells and the tumor microenvironment. In addition, the number of tumor-associated macrophages (TAMs) in the tumor microenvironment has also been demonstrated to correlate with tumor development. However, the relationship between tumor-secreted exosomes and TAM polarization under hypoxic conditions during tumor progression is not clear. Herein, we demonstrated that hypoxia induces the high expression of microRNA-940 (miR‑940) in exosomes derived from epithelial ovarian cancer (EOC). We also found that miR‑940 is highly expressed in exosomes isolated from ascites of EOC patients. Moreover, the overexpression of miR‑940 in macrophages delivered by exosomes stimulated M2 phenotype polarization, while the M2 subtype macrophages promoted EOC proliferation and migration. These results highlight the function of hypoxia in enhancing the high level of expression of miR‑940 in tumor exosomes taken up by macrophages. We also showed that the tumor-promoting function of miR‑940 is mediated by TAM polarization in EOC. These findings show that tumor-derived exosomal miR‑940 induced by hypoxia plays an important role in stimulating TAM polarization in the progression of EOC.


Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt).
Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle.


Family meetings in palliative care: are they effective?
Despite the promotion of family meetings as an essential tool for information sharing and planning in palliative care, minimal evidence exists to show their effectiveness. We sought to rectify this gap in evidence-based practice by evaluating recently developed clinical guidelines for facilitating family meetings. Palliative care nurses were trained to conduct family meetings using the guidelines. To assess the effectiveness of the guidelines, primary family carers who attended a family meeting completed a self-report instrument to measure unmet needs at three time periods: immediately before the meeting (T1), immediately after the meeting (T2) and two days after the meeting (T3). Phone interviews with carers were also conducted at T3. Patients, health professionals and family meeting facilitators were also invited to complete an evaluation form at T2. A focus group was conducted at the end of the project to gain reflections from the family meeting facilitators about their role, re-evaluate the family meeting clinical guidelines and discuss barriers and facilitators for ongoing implementation. Twenty family meetings were conducted at St Vincent's Hospital (Melbourne, Australia). A total of 42 participants were involved, including 20 family carers, 4 patients and 18 health professionals. Family carers reported a statistically significant increase in having their care needs met, from T1 to T2, which was maintained at T3; they also reported that the meetings were useful. Health professionals and patients advised that the meetings were well facilitated. The results from this pilot study indicate that family meetings, conducted using specific clinical practice guidelines, were useful and effective. However, more research is required to confirm these findings. Strategies for implementation and further research are outlined.


X Chromosome Inactivation Timing is Not eXACT: Implications for Autism Spectrum Disorders.
The etiology of autism spectrum disorders (ASD) is complex, involving different combinations of genetic and environmental factors. My lab's approach has been to investigate DNA methylation as a tractable genome-wide modification at the interface of these complex interactions, reflecting past and future events in the molecular pathogenesis of ASD. Since X-linked genes were enriched in DNA methylation differences discovered from cord blood from newborns later diagnosed with ASD, this has prompted me to review and revisit the recent advancements in the field of X chromosome inactivation (XCI), particularly in humans and other primates. In this Perspective, I compare XCI mechanisms in different mammalian species, including the finding of the noncoding transcript XACT associated with X chromosome erosion in human pluripotent stem cells and recent findings from non-human primate post-implantation embryos. I focus on the experimentally challenging peri- and post-implantation stages of human development when the timing of XCI is prolonged and imprecise in humans. Collectively, this research has raised some important unanswered questions involving biased sex ratios in human births and the male bias in the incidence of ASD.


Serological diagnosis of celiac disease.
Celiac disease CD is an inflammatory disease of the small intestine brought about by exposure to gluten in genetically predisposed individuals. Celiac disease most often presents with non specific, or extra-intestinal, manifestations and, consequently, the disease remains under diagnosed. Untreated CD is associated with high morbidity and, therefore, early diagnosis is essential. The availability of non-invasive and relatively cheap serological tests has made it possible to screen large numbers of patients and resulted in increased, and earlier, diagnosis of patients with CD. However, these tests have varying degrees of sensitivities and specificities and the results generated can lead to a lot of confusion with regards to the diagnosis, or exclusion, of CD. In the present review, we discuss in detail these tests and suggest how they can be used in screening patients for CD with the hope that such information will help clinicians to select the right tests and interpret the generated results more effectively, and thus lead to improved identification and treatment of patients with CD.


Comparative Assessment of the Utility of Anthropometric and Bioelectrical Impedance Indices as Potential Predictors of Hypertension within a Ghanaian Adult Population: A Cross-Sectional Study.
Hypertension is an important public health concern that is claiming millions of lives worldwide. In sub-Saharan African countries, where some of the highest prevalence rates are being recorded, sufficient attention has not been given to its control. The aim of this study was to determine the association and predictive potential of different anthropometric and bioelectrical impedance analysis (BIA) measures for hypertension. A total of 812 individuals (204 men and 608 women) were enrolled, and their blood pressure measurement was determined. Direct anthropometric measures (weight, height, waist circumference (WC), and hip circumference) and derived anthropometric measures (body mass index, conicity index, abdominal volume index (AVI), and body adiposity index) were determined. BIA indices investigated included visceral fat level (VF), percentage body fat (%BF), resting metabolic rate (RMR), and skeletal muscle mass. A prevalence of 31.28% was observed for hypertension in the total study population, with males having a slightly higher prevalence than females. Except for the skeletal muscle mass, all the other indices measured showed an increasing trend from normotension to prehypertension and hypertension. Age and visceral fat level showed the highest correlation with systolic blood pressure for both genders. Receiver operator characteristic analysis showed that age was the best predictor of hypertension in both genders, whereas, in predicting prehypertension, RMR was the best predictor in males, and WC was the best predictor in females. VF, WC, and AVI were other good predictors of hypertension in this study population. However, BMI and % BF had a low predictive value for hypertension. The result of this study shows that within this study population in addition to age, measures of central obesity rather than general obesity are the likely drivers of the hypertension epidemic; thus, measures aimed at controlling central obesity may offer some therapeutic and preventive advantage.


Six Hours after Infection, the Metabolic Changes Induced by WSSV Neutralize the Host's Oxidative Stress Defenses.
Levels of intracellular ROS (reactive oxygen species) were significantly increased in hemocytes collected from WSSV-infected shrimp within the first 30-120 min after infection. Measurement of the NADPH/NADP(+) and GSH/GSSG ratios revealed that after a significant imbalance toward the oxidized forms at 2 hpi, redox equilibrium was subsequently restored. Meanwhile, high levels of lactic acid production, elevated NADH/NAD(+) ratios, and metabolic changes in the glycolysis pathway show that the Warburg effect was triggered by the virus. The timing of these changes suggests that WSSV uses this metabolic shift into aerobic glycolysis to counteract the high levels of ROS produced in response to viral infection. We further show that if the Warburg effect is inhibited by chemical inhibition of the PI3K-Akt-mTOR signaling pathway, or if the pentose phosphate pathway is chemically inhibited, then in both cases, the production of intracellular ROS is sustained. We conclude that WSSV uses the PI3K-Akt-mTOR-regulated Warburg effect to restore host redox balance and to counter the ROS produced by the host in response to WSSV infection. We also found that pyruvate kinase activity was inhibited by WSSV. This inhibition is likely to increase the availability of the raw materials essential for WSSV gene expression and replication.


Functional expression of full-length TrkA in the prokaryotic host Magnetospirillum magneticum AMB-1 by using a magnetosome display system.
Tropomyosin receptor kinase A (TrkA), a receptor tyrosine kinase, is known to be associated with various diseases. Thus, TrkA has become a major drug-screening target for these diseases. Despite the fact that the production of recombinant proteins by prokaryotic hosts has advantages, such as fast growth and ease of genetic engineering, the efficient production of functional receptor tyrosine kinase by prokaryotic hosts remains a major experimental challenge. Here, we report the functional expression of full-length TrkA on magnetosomes in Magnetospirillum magneticum AMB-1 by using a magnetosome display system. TrkAwas fused with the magnetosome-localized protein Mms13 and expressed on magnetosome surfaces. Recombinant TrkA showed both nerve growth factor (NGF)-binding and autophosphorylation activities. TrkA expressed on magnetosomes has the potential to be used, not only for further functional analysis of TrkA, but also for ligand screening.


Orbital Venolymphatic Malformation Treated With Sodium Tetradecyl Sulfate: A Case Report.
Orbital and periorbital venolymphatic malformations (VLMs) are benign congenital vascular lesions and constitute 1%-3% of all orbital masses. Widespread facial venous malformations have a high incidence of associated intracranial developmental venous anomalies (DVAs). In such cases, there can be a sudden increase in proptosis following upper respiratory infection or minor trauma. Numerous percutaneous intralesional sclerosing agents like sodium tetradecyl sulfate (STS), bleomycin, doxycycline, ethanol, and OK-432 (Picibanil) have been used for treating VLMs. We hereby report a rare case of retro-orbital VLM treated successfully with STS injection and an isolated dural arterio-venous (AV) fistula in the same patient.


An assistive device for donning compression stockings.
Use of compression stockings has been demonstrated to be effective in helping heal venous leg ulcers and in reducing associated pain. During the past 5 years or more, patients suffering from edema, varices, or ulcers at the Taipei Veterans General Hospital and Taipei Vein Center, Taiwan, have been encouraged to use compression stockings. However, patients frequently reported difficulty donning the stockings, even with the help of a foot slip or slip-on stocking aid. Because a stocking aid did not function effectively above the heel position, the authors re-engineered and fabricated a reusable stocking aid that features a larger donning cup. This new device has been used successfully on at least 90 patients, who report enhanced willingness to use compression therapy and/or improved ease of stocking use as compared to previously used products or not using an assistive device. The design and use of this stocking aid is described.


BASH-deficient mice: limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation, in anti-NP response.
Signaling through the B cell antigen receptor (BCR) induces activation and proliferation of B cells, a response that requires the adaptor protein BASH (also known as BLNK/SLP-65). Although BASH and other molecules, such as Btk, PLCgamma2 and PKCbeta, are known to be essential for T cell-independent immune responses in vivo, their requirement during T cell-dependent immune responses, especially their role in antibody affinity-maturation and memory B cell generation remains unclear. In this study, we examined primary and memory immune responses to the T cell-dependent hapten antigen, (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to chicken gammaglobulin (CGG), in BASH-deficient mice on a C57BL/6 background. In the primary response, NP-specific IgM was barely produced and the typical anti-NP IgG1/lambda production was markedly attenuated, but kappa chain was unexpectedly over-represented in the anti-NP antibodies. In contrast, CGG-specific IgG1 was normally produced. In the memory response, IgG1/lambda antibody with high affinity to NP was produced at normal level in the mutant mice. The frequency and distribution of somatic mutations in the V(H)186.2 genes of the anti-NP IgG1/lambda antibody were also normal. These results indicate that BASH-mediated BCR signaling is dispensable for somatic hypermutation and affinity selection, as well as generation and response of memory B cells. Interestingly, mutated V(H) genes with the same clonal origin were prominent in the anti-NP antibodies of BASH-deficient mice, indicating that a limited number of original clones had been recruited into the memory compartment. Thus, the scarcity of specific clones in the primary repertoire and an impaired primary response is not detrimental to the quality and quantity of a memory response.


Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells.
There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation.


Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis.
Pulsatile secretion of cortisol (F) has not been documented in the newborn infant. Using repeated blood sampling and deconvolution analysis, we investigated F secretion and elimination dynamics in a group of five premature (gestational age, 24-34 weeks) and five term neonates. These infants had required placement of an umbilical arterial cannula for monitoring respiratory status, but were otherwise clinically stable. Blood samples were obtained at 15-min intervals for a 6-h period. All plasma F determinations were 58 nmol/L (2.1 micrograms/dL) or more, and pulsatile F secretion was observed in all infants. No significant differences were noted between the two groups with regard to 6-h mean plasma F concentration [350 +/- 129 (premature) vs. 277 +/- 54 nmol/L (term)], plasma corticosteroid-binding globulin (14 +/- 0 vs. 13 +/- 1 mg/L), F secretory burst frequency (4 +/- 0 vs. 5 +/- 1 bursts/6 h), mass of F secreted per burst [760 +/- 480 vs. 310 +/- 100 nmol/Lv [Lv, liter of F distribution volume)], F production rate (FPR; 2.7 +/- 1.4 vs. 1.1 +/- 0.2 mumol/Lv.6 h), or plasma F half-life (45 +/- 6 vs. 56 +/- 4 min). However, the premature infants had a significantly longer F secretory burst half-duration (63 +/- 18 vs. 6.7 +/- 4.0 min; P < 0.01) and a significantly lower maximal F secretory rate (9.4 +/- 3.4 vs. 100 +/- 26 nmol/Lv.min; P < 0.02) than the term infants. Body surface area and body weight were inversely correlated with F secretory burst half-duration (r = -0.74 and -0.75, respectively); both were also positively correlated with the maximal F secretory rate (r = 0.66 and 0.72). The two most premature infants had significantly greater mean plasma F and FPR than the other three premature and all of the term infants. Extrapolating to 24 h and correcting for the distribution volume of F and body surface area, we estimate FPR to be approximately 17-24 mumol/m2.24 h (6.6-8.8 mg/m2.24 h) for newborn infants of 34 weeks or more gestational age. These values are consistent with newer estimates of FPR in older children and adults determined using either deconvolution analysis or stable isotope dilution methods.


Origin and colocalization of CGRP- and SP-reactive nerves in cat airway epithelium.
A combination of neuroanatomic techniques was used to examine the origin and neuropeptide content of nerve fibers in the airway epithelium of adult cats. By the use of immunocytochemical methods, the peptides substance P (SP) and calcitonin gene-related peptide (CGRP) were colocalized in airway epithelial nerve fibers. Two days after wheat germ agglutinin (WGA) was injected into the nodose ganglion, fibers containing WGA immunoreactivity (IR) were detected in the airway epithelium. SP-like immunoreactivity (LI) and CGRP-LI were demonstrated separately in the WGA-IR fibers, establishing their origin from nerve cell bodies of nodose ganglion. Vagal transection inferior to the nodose ganglion reduced the number of SP- and CGRP-IR fibers by greater than 90% in ipsilateral airways. In contralateral airways, SP-IR fibers were substantially reduced, whereas the effect on CGRP-IR fibers was not statistically significant. Vagotomy superior to the nodose ganglion did not alter the density of peptide-IR fibers. The results prove that SP- and CGRP-IR nerve fibers of cat airway epithelium originate from nerve cell bodies in the nodose ganglion and that SP- and CGRP-like peptides may be stored together in some nerve fibers of the airway epithelium.


Functional Hydride Transfer by a Thiolate-Containing Model of Mono-Iron Hydrogenase featuring an Anthracene Scaffold.
We report the synthesis, X-ray structure and functional biomimetic activity of a model complex of mono-iron hydrogenase (Hmd). To achieve the desired biomimetic fac-CNS(thiolate) ligation motif, an anthracene framework is used to provide the requisite donors in a single chelate. A bulky aryl thiolate (ortho dimethylphenyl) is included to achieve mononuclearity. In addition to exhibiting structural (X-ray) and spectroscopic (NMR, IR) similarity to the enzyme, the complex is competent for H2 activation (heterolysis) and hydride transfer to a model substrate-mimicking the functional behavior of the enzyme in a biomimetic CNS coordination sphere for the first time.


Factors influencing performances and indicating risk of falls using the true Timed Up and Go test time of patients with hip fracture upon acute hospital discharge.
To examine the influence and risk of falls of individual factors on timed up and go test (TUG) times using standardized instructions in patients with hip fracture upon discharge from an acute orthopaedic hip fracture unit. Following instructions, the TUG was performed three times with a rollator (standardized aid), as fast as safely possible. Up to a 1-min rest was given after the first and second TUG trial. Multivariable linear regression analysis was used to investigate the factors influencing TUG-times and corresponding logistic analysis was used to investigate factors indicating risk of falls, using a cut-off of 24 s for TUG. A total of 181 patients (122 women), 60 years or older, with a mean (SD) age of 78.1 (9.1) years were studied. The fastest of three TUG trials performed within a mean of 10.0 (5.2) post-surgery days and used in analyses reached a mean of 25.6 (11.0) s. Multivariable regression analysis showed that greater age (B = 0.24; 2.4s more per decade older), a low pre-fracture function level (New Mobility Score <7 points, B = 6.4s more than high level), having a trochanteric fracture (B = 6.2 s, vs. cervical), and the post-surgery day of testing (B = 0.42, 4.2s per 10 days later) were independently associated with using more time for performing the TUG. Correspondingly, the same four factors indicated an increased risk of falls in the logistic analysis. The linear model explained 28% of the variance on TUG, while the accuracy of the logistic model to predict patients having TUG≥24 s was 69%. The age, pre-fracture function, fracture type and post-surgery day of TUG testing were identified as strong factors influencing TUG performances and TUG-times indicating risk of falls in patients with hip fracture. We suggest that these factors be considered when interpreting TUG test results and in further rehabilitation and fall prevention efforts.


Beetles (Insecta, Coleoptera) associated with pig carcasses exposed in a Caatinga area, Northeastern Brazil.
The species richness, abundance and seasonality of Coleoptera fauna associated with pig carcasses exposed in a Caatinga area were examined. Tray, pitfall and modified Shannon traps were settled together to collect these insects during two seasons (dry and rainy). 4,851 beetles were collected, belonging to 19 families and 88 species. Staphylinidae (2,184) and Histeridae (1,264) were the most abundant families and accounted for 71.1% of the specimens collected. Scarabaeidae (15) showed the highest species richness. The most abundant species were Atheta iheringi Bernhauer, 1908 (Staphylinidae) (1,685), Euspilotus sp. (Histeridae) (461), Stelidota geminata (Say, 1825) (Nitidulidae) (394), Xerosaprinus diptychus (Marseul, 1855) (Histeridae) (331) and Dermestes maculatus De Geer, 1774 (Dermestidae). Amongst these species, X. diptychus showed to be strongly influenced by seasonality, since 96.1% of the specimens were collected during the dry season.


Are papillary microcarcinomas of the thyroid gland revealed by cervical adenopathy more aggressive?
Therapeutic attitudes for papillary thyroid microcarcinoma (PTMC) range from observation alone to aggressive management. Clinicopathologic features, therapeutic options, and follow-up results are described in a series of PTMC revealed by cervical adenopathies. Twelve patients were enrolled in this retrospective study. They were all treated by total/near-total thyroidectomy with dissection of suspect cervical lymph nodes followed by radioactive iodine (RAI) and suppressive L-thyroxine therapies. Mean age at diagnosis was 32 years with a mean elapsed time to diagnosis of 45.3 months. Fine needle aspiration cytology and excisional biopsy of the lymph node led to a diagnosis in all cases. Cervical mass was ipsilateral to primary tumor in six patients (50%). Multifocality, bilaterality, and capsular invasion were encountered in 66.7, 66.7, and 41.7 per cent of patients, respectively. Lymph node involvement was bilateral in seven patients (58.3%) of whom thyroid foci were unilateral in two. No complications of thyroidectomy were encountered. At 60-month-follow up, no recurrence or metastasis was noted. PTMC revealed by cervical lymph node metastasis shows aggressive clinicopathologic features. They must be considered as papillary thyroid cancers and managed by total/near-total thyroidectomy with bilateral lymph node exploration followed by RAI therapy and suppressive L-thyroxine doses.


Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) reveals platelet activation in preeclampsia.
Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) is a membrane protein receptor found in α-granules of megakaryocytes and platelets. Upon platelet activation TLT-1 is rapidly relocated to the surface of platelets. In plasma, a soluble form of TLT-1 (sTLT-1) is present. Plasma levels of sTLT-1 are significantly elevated in thrombotic diseases. In the present study, we investigated to whether TLT-1 reflects platelet activation in pregnant women with preeclampsia. We studied 30 preeclamptic patients who were matched with 30 normotensive pregnant women and 30 non-pregnant controls. Basal TLT-1, P-selectin, and CD63 expressions on platelets were analyzed with the use of flow-cytometry (FCM). Platelet reactivity was induced by thrombin receptor activation peptide and determined by FCM. Plasma concentrations of sTLT-1 and soluble P-selectin (sP-selectin) were measured by an enzyme-linked immunosorbent assay. Results show that basal platelet expression of TLT-1, P-selectin and CD63 were increased in women with preeclampsia (PE) compared with normotensive pregnant women (NP). Platelets from PE women and NP women were more responsive compared to from nonpregnant women controls (NC), and which was demonstrated by increased expression of TLT-1, P-selectin, and CD63 upon stimulation in vitro. Plasma concentration of sTLT-1 was greater in PE women compared to NP women and NC women. Plasma sP-selectin level was higher in pregnant women than in nonpregnant women, but there were no significant differences between PE and NP women. In summary, our results revealed that platelet activation is prominent in preeclampsia, TLT-1 reflects platelet activation and may be a useful indicator for preeclampsia.


Transport phenomena governing nicotine emissions from electronic cigarettes: model formulation and experimental investigation.
Electronic cigarettes (ECIGs) electrically heat and aerosolize a liquid containing propylene glycol (PG), vegetable glycerin (VG), flavorants, water, and nicotine. ECIG effects and proposed methods to regulate them are controversial. One regulatory focal point involves nicotine emissions. We describe a mathematical model that predicts ECIG nicotine emissions. The model computes the vaporization rate of individual species by numerically solving the unsteady species and energy conservation equations. To validate model predictions, yields of nicotine, total particulate matter, PG, and VG were measured while manipulating puff topography, electrical power, and liquid composition across 100 conditions. Nicotine flux, the rate at which nicotine is emitted per unit time, was the primary outcome. Across conditions, the measured and computed nicotine flux were highly correlated (r = 0.85, p<.0001). As predicted, device power, nicotine concentration, PG/VG ratio, and puff duration influenced nicotine flux (p<.05), while water content and puff velocity did not. Additional empirical investigation revealed that PG/VG liquids act as ideal solutions, that liquid vaporization accounts for more than 95% of ECIG aerosol mass emissions, and that as device power increases the aerosol composition shifts towards the less volatile components of the parent liquid. To the extent that ECIG regulations focus on nicotine emissions, mathematical models like this one can be used to predict ECIG nicotine emissions and to test the effects of proposed regulation of factors that influence nicotine flux.


Smoking habits in patients diagnosed with ANCA associated small vessel vasculitis.
To study the prevalence of smoking at onset of symptoms in patients with small vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA). A retrospective study, in 197 patients with ANCA associated vasculitis, of the history of cigarette smoking at onset of symptoms. Prevalence of smoking in patients with ANCA associated vasculitis was compared with age-specific values for the general population in Germany. 27 (14%) patients were smokers at the time of first disease manifestation (p < 0.001, compared with the entire population); 54 (27%) had smoked previously with 1-110 pack-years (median 18) but had stopped > or = 2 years before onset of vasculitis; 116 (59%) patients were lifelong non-smokers. At onset of symptoms, active smokers were younger (median age 42 years) than patients with vasculitis (median 54 years, p < 0.01, Mann-Whitney U test) with a lower percentage of women (15%, p < 0.005, Fisher's exact test) than in the entire group (47%). Smokers, non-smokers, or ex-smokers did not differ in organ manifestation, mortality, and development of end stage renal disease and relapse rate. The proportion of active smokers in the group of patients with ANCA associated vasculitis is significantly lower than in the entire population. Cigarette smoking may be associated with a reduced risk of ANCA associated vasculitis.


In Vivo Molecular Signatures of Cerebellar Pathology in Spinocerebellar Ataxia Type 3.
No treatment exists for the most common dominantly inherited ataxia Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3). Successful evaluation of candidate therapeutics will be facilitated by validated noninvasive biomarkers of disease pathology recapitulated by animal models. We sought to identify shared in vivo neurochemical signatures in two mouse models of SCA3 that reflect the human disease pathology. Cerebellar neurochemical concentrations in homozygous YACMJD84.2 (Q84/Q84) and hemizygous CMVMJD135 (Q135) mice were measured by in vivo magnetic resonance spectroscopy at 9.4 tesla. To validate the neurochemical biomarkers, levels of neurofilament medium (NFL; indicator of neuroaxonal integrity) and myelin basic protein (MBP; indicator of myelination) were measured in cerebellar lysates from a subset of mice and patients with SCA3. Finally, NFL and MBP levels were measured in the cerebellar extracts of Q84/Q84 mice upon silencing of the mutant ATXN3 gene. Both Q84/Q84 and Q135 mice displayed lower N-acetylaspartate than wild-type littermates, indicating neuroaxonal loss/dysfunction, and lower myo-inositol and total choline, indicating disturbances in phospholipid membrane metabolism and demyelination. Cerebellar NFL and MBP levels were accordingly lower in both models as well as in the cerebellar cortex of patients with SCA3 than controls. Importantly, N-acetylaspartate and total choline correlated with NFL and MPB, respectively, in Q135 mice. Long-term sustained RNA interference (RNAi)-mediated reduction of ATXN3 levels increased NFL and MBP in Q84/Q84 cerebella. N-acetylaspartate, myo-inositol, and total choline levels in the cerebellum are candidate biomarkers of neuroaxonal and oligodendrocyte pathology in SCA3, aspects of pathology that are reversible by RNAi therapy. © 2020 International Parkinson and Movement Disorder Society.


On the Reliability of the Notion of Native Signer and Its Risks.
Who is a native signer? Since around 95% of deaf infants are born into a hearing family, deaf signers are exposed to a sign language at various moments of their life, and not only from birth. Moreover, the linguistic input they are exposed to is not always a fully fledged natural sign language. In this situation, is the notion of native signer as someone exposed to language from birth of any use? We review the results of the first large-scale cross-linguistic investigation on the effects of age of exposure to sign language. This research involved about 45 Deaf adult signers in each of three sign languages (Catalan Sign Language, French Sign Language, and Italian Sign Language). Across the three languages, participants were divided into three groups - those exposed from birth, those between 1 and 5 years of age, and those exposed between 6 and 15 years of age - and received a battery of tests designed for each language targeting various aspects of morphosyntactic competence. In particular, the tests focused on both those morphosyntactic phenomena that are known from the spoken language literature to be good detectors of language impairment or delay (i.e., wh-interrogatives and relative clauses) and on morphosyntactic phenomena that are sign language specific (i.e., role shift and directional verbs). The results showed a clear effect of being native, with significant differences across languages and tests between signers exposed to sign language from birth and those exposed in the 1st years of life. This confirms the life-long importance of language exposure from birth and the reliability of the notion of "nativeness", at least for syntax. On the other hand, while in most domains the differences observed between populations might be differences in performance, for some specific constructions, signers belonging to the three groups may have different grammars. This latter finding challenges the generalized use of native signers' grammar as the baseline for language description and language assessment.


[Carnitine in therapy of placental insufficiency--initial experiences].
Carnitine (3-hydroxy and 4-trimethylaminobutyrate) present in all living cells, plays an important role in the oxidation of fatty acids. It is known that high dose carnitine activates surfactant synthesis. Given to women with imminent premature delivery, its benefit on the post natal period is proved. Own studies showed an increased need of carnitine during pregnancy. Therefore the questions rose if carnitine substitution improves placental insufficiency. 15 pregnant women were treated with 2 x 1 g carnitine orally for one week and with 1 x 1 g carnitine during the following 7 days when their fetus showed a retardation of 1-3 weeks. The control group were 15 untreated patients with the same problems of retardation. The placental insufficiency was diagnosed by fetometry, by blood parameters and the doppler ultrasound flow measurement. In the group of the treated patients 11 out of 15 showed an improvement, in 4 patients no effect of carnitine was seen and in 1 patient the retardation increased. In the control group 8 out of 15 patients showed a spontaneous improvement of fetal growth, 2 women did not have a change in their retardation and 5 patients had to be hospitalized because of increasing placental insufficiency. Inspite of the small number of patients a tendency towards a profit in carnitine treatment for placental insufficiency seems to be real.


Prognostic Value of Prognostic Nutritional Index in Patients With Colorectal Cancer Undergoing Surgical Treatment.
To investigate the relationship between prognostic nutritional index (PNI) and the survival of patients with colorectal cancer (CRC) undergoing surgical treatment. In total 1,014 CRC patients who underwent surgical treatment were enrolled. Logistic regression analysis was used to identify the features that influenced postoperative complications in CRC patients. Restricted cubic spline was used to assess the dose-response relationship between PNI and survival in CRC patients. Kaplan-Meier method and log-rank test were used to compare survival differences between groups of CRC patients. Cox proportional risk regression models was used to assess independent risk factors for progression-free survival (PFS) and overall survival (OS) of CRC patients. Low PNI was associated with high tumor burden, invasive pathological features, and poor host status. Compared with patients with high PNI, patients with low PNI have a higher incidence of complications and longer hospital stay. Low PNI was an independent risk factor for postoperative complications in CRC patients. for every SD increased in PNI, the risk of poor prognosis for CRC patients was reduced by 2.3% (HR = 0.977, 95%CI = 0.962-0.993, p = 0.004) in PFS, and 2.3% (HR = 0.977, 95%CI = 0.962-0.993, p = 0.004) in OS. PNI was an independent prognostic factor affecting the PFS and OS of CRC patients. Finally, we constructed the PNI-based nomograms to predict postoperative complications, 1-5 years PFS and OS in CRC patients. Concordance index and calibration curve indicated that the PNI-based nomograms have moderate prediction accuracy. PNI is an independent risk factor affecting postoperative complications, PFS and OS of CRC patients, and is a useful supplement to the TNM stage.


TSLP-activated dendritic cells induce T helper type 2 inflammation in Aspergillus fumigatus keratitis.
Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which is secreted by epithelial cells under the stimulation of Toll-like receptor (TLR) ligands. Dendritic cells (DCs) which express the thymic stromal lymphopoietin receptor (TSLPR) can be activated by TSLP. Mature DCs can express the OX40 ligand, which has the ability to combine with OX40 on the surface of T cells to stimulate T cell proliferation. TSLP secreted by corneal epithelial cells can engage in the process of T helper type 2 (Th2) inflammation in Aspergillus fumigatus keratitis, but the mechanism remains unclear. We demonstrated that in A. fumigatus-infected corneas, DCs aggregated, matured, and gradually migrated not only from the basement membrane to the corneal epithelium, but also from the corneal limbus to the central cornea. Mature DCs secreted Th2-attracting chemokines, the thymus and activation-regulated chemokine (TARC), and the macrophage-derived chemokine (MDC), encouraging the secretion of TNF-α and Th2 cytokine Interleukin (IL) -4, IL-5, and IL-13. The above processes were all restricted with subconjunctivally injection of TSLP siRNA, while they were strengthened with the injection of rTSLP. We demonstrated that in A. fumigatus keratitis, TSLP, through combination with TSLPR on the surface of DCs, induced DC aggregation, maturation, and migration, and then the mature DCs secreted Th2-attracting chemokines, promoting the secretion of proinflammatory cytokine TNF-α and Th2 cytokines, which finally induced Th2 inflammation.


A new hexahydrobenzopyran derivative from the gorgonian-derived Fungus Eutypella sp.
A new hexahydrobenzopyran derivative cytosporin L (1), and another eight known compounds were isolated from the gorgonian-derived fungus Eutypella sp. collected from the South China Sea. The structure of 1 was elucidated by comprehensive spectroscopic data. The absolute configuration of 1 was determined by a chemical reaction and the modified Mosher's method. The isolated secondary metabolites were evaluated for their antibacterial activities. Compound 1 showed antibacterial activity towards Micrococcus lysodeikticus and Enterobacter aerogenes with the same MIC values of 3.12 μM. Compounds 1-3 were evaluated for antiviral activities. Compounds 1 and 2 obviously inhibited the respiratory syncytial virus (RSV) with the IC50 values of 72.01 and 30.25 μM, respectively.


[Secretion of incretin hormones in people having risk factors for type 2 diabetes mellitus].
To study the secretion of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP),and glucagon- like peptide 2 (GLP-2) in response to a carbohydrate load in people with risk factors for type 2 diabetes mellitus (DM2) in relation to the type of carbohydrate metabolic disturbances and age. One hundred and twenty-seven patients having DM2 risk factors who had not previously received glucose- lowering therapy underwent an oral glucose tolerance test (OGTT). The plasma levels of glucose, insulin, glucagon, GLP-1, GIP, and GLP-2 were determined at 0, 30, and 120 minutes of the test. According to the findings, the patients were divided into 3 groups: 1) normal glucose tolerance; 2) prediabetic states (impaired glucose tolerance and/or impaired fasting glycemia); 3) new-onset DM2. OGTT showed that the secretion of GLP-1 was lower and that of GIP and GLP-2 was higher in patients with DM2. GLP-1 secretion decreased with patient age. During OGTT, there is a statistically significantly difference in the secretion of incretin hormones in persons with varying degrees of carbohydrate metabolic disturbances: the peak GLP-1 secretion is the highest in healthy individuals and lowest in the patients with DM2; on the contrary, the peak GLP2 and GIP secretions are the highest in the patients with DM2. This may suggest that GLP-1 and the two other hormones (GLP-2 and GIP) show opposite effect in the regulatory mechanisms of carbohydrate metabolism. GLP-1 secretion is decreased with age, which may be one of the reasons for the higher prevalence of DM2 among the elderly.


A rare manifestation of nail changes with docetaxel therapy.
A 60-year-old African American man presented to the dermatology clinic for evaluation of skin and nail changes associated with docetaxel therapy for adenocarcinoma of the prostate. Previous treatment cycles ofdocetaxel had resulted in hyperpigmented patches and linear streaks on his arms where he received infusions, as well as nail changes, including longitudinal melanonychia and onycholysis of his great toenails. At his latest visit, he reported recently noticing a new bluish discoloration of his lunulae that had developed during the past 3 months, the time corresponding to his most recent docetaxel treatment cycle (Figure). The patient's history did not reveal any recent medication changes, ingestion of known lunula-discoloring agents, or any silver-containing compounds. On examination, the patient's observation was confirmed, as the lunulae on both his right and left thumb were found to have a marked blue discoloration to them. The patient was treated with observation as the discoloration was not bothersome to him, and on routine follow-up for an unrelated skin complaint, the patient's nail beds had returned to their normal color, approximately 3 months after discontinuation of the docetaxel therapy, according to the patient.


Antinociceptive and anti-inflammatory activities of Geranium bellum and its isolated compounds.
Geranium bellum Rose, locally known as "Pata de león", is a perennial plant distributed in the mountains of Hidalgo, Mexico. It is widely used in Mexican traditional medicine to treat fever, pain, and gastrointestinal disorders. To date, there are not published studies regarding the in vivo antinociceptive and anti-inflammatory potential of the acetone-aqueous extract from the aerial parts of G. bellum. Antinociceptive effects of the acetone-aqueous G. bellum (AGB) extract and the isolated compounds were assessed using experimental pain models, including thermal nociception like hot plate test, and chemical nociception induced by intraperitoneal acetic acid or subplantar formalin injection in vivo. The anti-inflammatory properties of the extract were studied using systemic administration in carrageenan-induced paw edema. Intra-gastric administration of AGB (75, 150, and 300 mg/kg) showed a dose-dependent antinociceptive effect in intraperitoneal acetic acid (writhing), thermal nociception in CD1 mice, and subplantar formalin models, as well as anti-inflammatory effect in carrageenan- induced paw edema in Wistar rats. Geraniin and quercetin showed the highest antinociceptive activity in writhing test, whereas ellagic acid was the most active compound in the hot plate model. These studies provide evidences that G. bellum shows antinociceptive and anti- inflammatory effects, and gives support to its use in treating pain in Mexican traditional medicine.


Patient-reported outcomes after a distal radius fracture in adults: a 3-4 years follow-up.
Background and purpose - There are few reports on the outcome of distal radius fractures after 1 year. Therefore we investigated the long-term patient-reported functional outcome and health-related quality of life after a distal radius fracture in adults. Patients and methods - We reviewed 823 patients, treated either nonoperatively or operatively in 2012. After a mean follow-up of 3.8 years 285 patients (35%) completed the Patient-Rated Wrist Evaluation (PRWE) and EuroQol-5D. Results - The mean PRWE score was 11. The mean EQ-5D index value was 0.88 and the mean EQ VAS for self-rated health status was 80. Nonoperatively treated type A and type B fractures had lower PRWE scores compared with operatively treated patients, whereas the EQ-5D was similar between groups. The EQ VAS for patients aged 65 and older was statistically significantly lower than that of younger patients. Interpretation - Patients had a good overall long-term functional outcome after a distal radius fracture. Patients with fractures that were possible to treat nonoperatively had less pain and better wrist function after long-term follow-up than patients who needed surgical fixation.


Hip protectors for preventing hip fractures in the elderly.
Hip fracture in the elderly usually results from a fall on the hip. Hip protectors have been advocated as a means to reduce the risk of sustaining a hip fracture. To determine if external hip protectors reduce the incidence of hip fractures in elderly persons following a fall. We searched the Cochrane Musculoskeletal Injuries Group trials register (February 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February Week 2 2004), EMBASE (1988 to 2004 Week 08), CINAHL (1982 to February Week 2 2004), other databases and reference lists of relevant articles. We also contacted trialists. All randomised or quasi-randomised controlled trials comparing the use of hip protectors with a control group. Two reviewers independently assessed trial quality and extracted data. We sought additional information from all trialists. An additional trial with 4169 participants was included in this update, giving a total of 14 included trials. One, which was a study of compliance (adherence) lasting 12 weeks, contributed no fracture outcome data. Five studies involving 4316 participants were cluster randomised by care unit, nursing home or nursing home ward rather than by the individual. Each of these studies reported a reduced incidence of hip fractures within those units allocated to receive the protectors. Because the majority of these trials had not been analysed to allow for clustering, pooling of their results was not undertaken. Pooling of data from five individually randomised trials conducted in nursing/residential care settings (1426 participants) showed no significant reduction in hip fracture incidence (hip protectors 37/822, controls 40/604, relative risk (RR) 0.83, 95% confidence interval (CI) 0.54 to 1.29). Three individually randomised trials of 5135 community dwelling participants, reported no reduction in hip fracture incidence with the hip protectors (RR 1.16, 95% CI 0.85 to 1.59). No important adverse effects of the hip protectors were reported but compliance, particularly in the long term, was poor. There is no evidence of effectiveness of hip protectors from studies in which randomisation was by individual patient within an institution, or for those living in their own homes. Data from cluster randomised studies indicate that, for those living in institutional care with a high background incidence of hip fracture, a programme of providing hip protectors appears to reduce the incidence of hip fractures. Acceptability by users of the protectors remains a problem, due to discomfort and practicality.