Andexanet Alfa for Urgent Reversal of Apixaban Before Aortic Surgery Requiring Cardiopulmonary Bypass: A Case Report.
Andexanet alfa is a recombinant factor Xa decoy molecule capable of reversing direct and indirect factor Xa-inhibiting anticoagulants. We present an adult patient on apixaban for nonvalvular atrial fibrillation who required urgent reoperative aortic surgery for an aortic root pseudoaneurysm. Apixaban was reversed with andexanet alfa. A second dose of andexanet alfa was required before surgical incision for persistently elevated antifactor Xa levels. Intraoperative management required use of cardiopulmonary bypass (CPB). No major adverse cardiovascular, cerebrovascular, hemorrhagic, or thromboembolic events were observed.


Patient Satisfaction with Pain Level in Patients with Cancer.
Interest in satisfaction with pain management as a pain-related outcome variable wavered when investigators found poor correlations with pain intensity when they measured satisfaction with pain management rather than satisfaction with pain level. The aim was to explore the relationship between satisfaction with pain level and pain intensity among patients receiving ongoing outpatient cancer care. In a comparative, secondary data analysis of a cross-sectional sample of 806 cancer patients (57% male, mean age 56 ± 13 years, 77% Caucasian), the authors measured satisfaction with pain level as a single item (yes, no, not sure) and pain intensity as an average of current, least, and worst pain intensity (all 0-10 scales) in the past 24 hours. Of the 806 participants, 447 (56%) subjects were satisfied with their pain level, 291 (36%) were not satisfied and 68 (8%) were not sure. Satisfaction was moderately correlated with API (rho = -0.43, p < .001). Patients satisfied with their pain levels reported statistically lower mean API scores (2.26 ± 1.70) than those who were not satisfied (4.68 ± 2.07) or not sure (4.21 ± 2.2.1), p < .001. With pair wise post hoc comparisons, mean API scores of satisfied patients were significantly lower than those who were not satisfied or not sure. In contrast with other researchers who have not found associations between satisfaction with pain management and pain intensity, the authors demonstrated that when satisfaction is measured specifically, patients with higher pain intensity are not satisfied. The authors recommend that researchers use "satisfaction with pain level" instead of "satisfaction with pain management" as the pain satisfaction outcome.


Is the FeO2(-) anion bent or linear?
FeO(2)(-) anions were produced by co-condensation of laser-ablated iron atoms and electrons with dioxygen in excess argon at 6 K. A photosensitive absorption at 870.6 cm(-1) is assigned to the antisymmetric OFeO stretching vibration (nu(3)) of the inserted FeO(2)(-) anion trapped in solid argon. On the basis of the observed nu(3) vibrational frequencies for Fe(16)O(2) and Fe(18)O(2), the anion is estimated to be linear. Due to the severe symmetry-breaking problems of the reference wave function, calculations with single-reference methods, including various DFT and post-HF methods, are unreliable for this molecule. However, the state-averaged multireference MRCI method, which incorporates both dynamical and nondynamical correlations, predicted that the anion has a linear doublet ground state, consistent with the experimental observations.


Early Perioperative Management After Pediatric Cardiac Surgery: Review at PCICS 2014.
The sessions of the symposium held in December 2014 allow us to capitalize on the shared knowledge and experience that arise from both cardiac anesthesia and cardiac intensive care. During this session, topics that crossed traditional boundaries of pediatric cardiac intensive care and pediatric cardiac anesthesia were presented and discussed. This article summarizes the five topics presented at the symposium.


The picture of the prostatic lymphokine network is becoming increasingly complex.
The immunology of the prostate has recently developed into a new field of research in urology. Although we do not yet understand why the leukocyte population increases, we know that most resected prostate tissue shows signs of an inflammatory reaction. Different types of inflammation exist, and must be distinguished carefully according to distribution and location of leukocytes and histology of the surrounding tissue. This article reviews recent findings and discusses the complex mechanisms involved in the prostatic inflammatory response. The roles of estrogen, interleukin (IL)-6, IL-8, IL-15, and IL-17 are examined.


[Inflammatory myofibroblastic tumor of the larynx].
Inflammatory myofibroblastic tumor (IMT) of the larynx is a rare borderline lesion composed of myofibroblastic and inflammatory cells. We presented a case of 77-year-old male with hoarseness for about three months. Laryngoscopy showed a polypoid tumor originated from the anterior commissure with glottic projection. Grossly, the tumor was 22 x 15 mm, whitish, oval nodus with firm consistency. Histologically, the lesion was composed of spindled to stellate cells arranged in a fascicular to storiform pattern and inflammatory cells: lymphocytes, histiocytes, plasma cells and neutrophils. The stroma was fibromyxoid and collagenous. Immunohistochemically, tumor cells showed strong positivity for actin and vimentin and negativity for cytokeratin, CD34, S100 and desmin. The proliferation (Ki67) was less than 10%. Inflammatory myofibroblastic tumor may be mistaken as a malignancy and the differential diagnosis can be difficult without immunohistochemistry. It is critical to recognize this uncommon entity to avoid unnecessary aggressive treatment.


Chronic Tubulo-interstitial Nephropathy with Hepatic Involvement in Children.
The clinical, biochemical and histological data are reported in a female infant with rapidly progressive renal failure, hepatosplenomegaly and death at the age of 2 years. This case represents another example of the newly described entity "chronic tubulo-interstitial nephritis with hepatic involvement" and the only reported case of this kind from this part of the world.


[Indications of lasers treatment for lymphatic malformations].
Cutaneous dermatologic lesions of LM, in type of superficial, translucent, localized or diffuse vesicles, are accessible to laser treatment. The useful lasers are essentially laser CO(2), and rarely pulsed dye laser and the Nd: YAG. Treatment by laser allows to obtain the ablation of vesicles by limiting aftereffects (scare) and so to dry up the transcutaneous lymphatic liquid. However laser has no action on the deep constituent of the LM and it's why medium and long term recurrences are inevitable. Finally, the indication of the laser must be retained only as a supplement to the surgery and has to be done by experimented persons.


GLABRA2 Directly Suppresses Basic Helix-Loop-Helix Transcription Factor Genes with Diverse Functions in Root Hair Development.
The Arabidopsis thaliana GLABRA2 (GL2) gene encodes a transcription factor involved in the cell differentiation of various epidermal tissues. During root hair pattern formation, GL2 suppresses root hair development in non-hair cells, acting as a node between the gene regulatory networks for cell fate determination and cell differentiation. Despite the importance of GL2 function, its molecular basis remains obscure because the GL2 target genes leading to the network for cell differentiation are unknown. We identified five basic helix-loop-helix (bHLH) transcription factor genes (ROOT HAIR DEFECTIVE6 [RHD6], RHD6-LIKE1 [RSL1], RSL2, Lj-RHL1-LIKE1 [LRL1], and LRL2) as GL2 direct targets using transcriptional and posttranslational induction systems. Chromatin immunoprecipitation analysis confirmed GL2 binding to upstream regions of these genes in planta. Reporter gene analyses showed that these genes are expressed in various stages of root hair development and are suppressed by GL2 in non-hair cells. GL2 promoter-driven GFP fusions of LRL1 and LRL2, but not those of the other bHLH proteins, conferred root hair development on non-hair cells. These results indicate that GL2 directly suppresses bHLH genes with diverse functions in root hair development.


[A clinical analysis of 50 cases of medicament-like dermatitis due to trichloroethylene].
To investigate the clinical manifestations, complications and treatment of medicament-like dermatitis due to trichloroethylene (TCE), so as to provide basis for studying its etiology and mechanism. Fifty patients with dermatitis due to TCE from 1997 to 2000 were analysed retrospectively. The occurrence of the dermatitis was not parallel to TCE exposure levels, without significant dose-effect relationship. This disease could be caused by both inhalation and skin exposure. The latency period of TCE dermatitis ranged from 5 to 66 days, and the average was 31.5 d (Medium). The major clinical manifestations included skin lesions, fever, superficial lymph node swelling and liver dysfunction. Infection was the major complication. Glucocorticoid was effective for treatment of this disease. The clinical manifestations due to TCE exposure were similar to dermatitis medicamentosa. The major clinical types of TCE dermatitis included exfoliative dermatitis and erythema multiforme. The dermatitis is considered to be mediated by delayed-type (IV) hypersensitivity. The key factors to treat this disease successfully included the use of glucocorticoid in time with sufficient dose and full course, professional skin care, active treatment to protect the liver and to avoid infection.


Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion.
IA-2 is a major autoantigen in type 1 diabetes. Autoantibodies to IA-2 appear years before the development of clinical disease and are being widely used as predictive markers to identify individuals at risk for developing type 1 diabetes. IA-2 is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is an integral component of secretory granules in neuroendocrine cells. To study its function, we generated IA-2-deficient mice. Northern and Western blot analysis showed that neither IA-2 mRNA nor protein was expressed. Physical examination of the IA-2(- /-) animals and histological examination of tissues failed to reveal any abnormalities. Nonfasting blood glucose levels, measured over 6 months, were slightly elevated in male IA-2(-/-) as compared to IA-2(+ /+) littermates, but remained within the nondiabetic range. Glucose tolerance tests, however, revealed statistically significant elevation of glucose in both male and female IA-2(-/-) mice and depressed insulin release. In vitro glucose stimulation of isolated islets showed that male and female mice carrying the disrupted gene released 48% (P < 0.001) and 42% (P < 0.01) less insulin, respectively, than mice carrying the wild-type gene. We concluded that IA-2 is involved in glucose-stimulated insulin secretion.


Radiating and nonradiating behavior of hyperbolic-secant, raised-cosine, and Gaussian input light pulses in dispersion-managed fiber systems.
We address the problem of optical light pulses, called dressed pulses, which do not match the stationary pulse profile of a dispersion-managed (DM) fiber system and we theoretically analyze the associated radiation. Comparing hyperbolic-secant, raised-cosine, and Gaussian pulse envelopes, we show that the general radiation figure is highly sensitive to the input pulse profile. As common general features for these pulse profiles, we find a rich variety of dynamical states that includes weak-, moderate-, and strong-radiation states, depending on the map strength of the DM fiber system. We demonstrate the existence of two intervals of map strengths where the emitted radiation is of considerably low level. The first interval falls in a region of small map strengths where pulses are weakly dressed. In contrast, the second window of low radiation appears in the map strength region corresponding to strongly dressed pulses. As a major difference with respect to the pulse profile, we find that light pulses with Gaussian input profile produce less radiation in the fiber system than hyperbolic-secant or raised-cosine pulses can do. In particular, at the lower edge of the second window of low radiation, Gaussian light pulses with large initial dressing acquire the best ability to execute a stable nonradiative propagation over transoceanic distances.


Reevaluation of zinc deficiency on concanavalin-A-induced rat spleen lymphocyte proliferation.
Zinc concentrations of serum, nonlymphoid and lymphoid tissues, and the responsiveness of concanavalin-A (Con-A)-stimulated spleen lymphocytes (SL) and cervical lymph node cells ( CLNC ) from ad libitum-fed zinc-deficient (ZD), pair-fed (PF) and ad libitum-fed zinc-adequate rats (AL) were determined. In vitro effects of serum from ZD, PF and AL rats on responsiveness of Con-A-stimulated SL and CLNC were determined. Weanling male Long-Evans rats were fed ad libitum zinc-deficient (less than 1.0 microgram Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 7-42 days. Effects of undernutrition on test parameters were determined on PF rats, which received a restricted zinc-adequate diet (restricted in amount to that consumed by ZD rats). Growth, food intake and zinc concentrations in serum, liver and pancreas were significantly depressed in ZD and PF rats. Zinc per gram of thymus tissue and per number of SL was elevated in ZD and PF rats. Spleen lymphocytes from ZD and PF rats displayed equivalent to significantly increased levels of proliferation following stimulation with Con-A. [3H]Thymidine incorporation by Con-A-stimulated SL and CLNC from ZD, PF and AL rats was not significantly different when cultured in medium containing serum from ZD, PF and AL rats. The present study shows that zinc deficiency causes major changes in total-body and organ growth but minor changes in zinc content and mitogen-induced proliferation of lymphocytes.


Investing in mini-livestock production for food security and carbon neutrality in China.
Future food farming technology faces challenges that must integrate the core goal of keeping the global temperature increase within 1.5 °C without reducing food security and nutrition. Here, we show that boosting the production of insects and earthworms based on food waste and livestock manure to provide food and feed in China will greatly contribute to meeting the country's food security and carbon neutrality pledges. By substituting domestic products with mini-livestock (defined as earthworms and insects produced for food or feed) protein and utilizing the recovered land for bioenergy production plus carbon capture and storage, China's agricultural sector could become carbon-neutral and reduce feed protein imports to near zero. This structural change may lead to reducing greenhouse gas emissions by 2,350 Tg CO2eq per year globally when both domestic and imported products are substituted. Overall, the success of mini-livestock protein production in achieving carbon neutrality and food security for China and its major trading partners depends on how the substitution strategies will be implemented and how the recovered agricultural land will be managed, e.g., free use for afforestation and bioenergy or by restricting this land to food crop use. Using China as an example, this study also demonstrates the potential of mini-livestock for decreasing the environmental burden of food production in general.


Stability of access resistance during haemodialysis.
Access blood flow (Qac) is considered a useful indicator in the surveillance of haemodialysis access function. However, changes in Qac may be due to changes in blood pressure and/or to changes in access resistance (AR). Weekly readings of Qac, cardiac output, and arterial blood pressure measured early and late during haemodialysis were obtained in 11 patients for a period of 3 weeks. Qac was determined from thermodilution of extracorporeal blood returning to the patient with reversed placement of blood lines and by measurement of arterial and venous blood temperatures in the extracorporeal circulation. Data are given as mean +/- SE. Qac dropped as mean arterial pressure (MAP) and total peripheral resistance (TPR) decreased, but increased when MAP and TPR increased. Linear regressions between the change in access flow and the change in MAP (deltaQac%=0.80*deltaMAP%-1.6, r2=0.39), and the change in TPR (deltaQac%= 0.54*deltaTPR%-9.2, r2=0.35) respectively, were significant (P<0.001). Whereas Qac significantly decreased (-8.4+/-3.3%, P<0.01) during the same treatment, AR remained unchanged (4.7+/-3.2%; P=NS). AR for all studies was 16.5+/-1.0 peripheral resistance units (1 PRU=2.226 kPa min l(-1)). There was a trend for resistance to increase (5.1+/-2.6%, P=NS) and for flow to decrease (-6.1+/-2.3%, P=NS) during the 3 weeks of the study. Qac measured during haemodialysis is variable and depends on haemodynamics, but AR is constant. AR is related to the physical structure of the peripheral access. Because of its intradialytic stability AR may be better suited as an indicator of access function.


K-ras oncogene mutations in neoplasias of kidney transplanted patients: preliminary results with a new technique.
K-ras oncogene activations by point mutations are frequent in many forms of human cancers but there is a special category of cancers occurring in immunosuppressed patients after kidney transplantation in which the frequency of K-ras oncogene activation has not been fully studied. We used a new sensitive and easy method for the detection of this mutation, and in 8 DNA samples studied from various neoplasias of 8 patients after kidney transplantation, we found 4 mutations. Our preliminary results indicate that the activation of K-ras oncogene at codon 12, is a common event among the kidney transplanted patients who present a neoplasia, even in the least aggressive forms of the disease, contrary to the sporadic cases.


Bi-level Mixed-Integer Data-Driven Optimization of Integrated Planning and Scheduling Problems.
Supply chain management is an interconnected problem that requires the coordination of various decisions and elements across long-term (i.e., supply chain structure), medium-term (i.e., production planning), and short-term (i.e., production scheduling) operations. Traditionally, decision-making strategies for such problems follow a sequential approach where longer-term decisions are made first and implemented at lower levels, accordingly. However, there are shared variables across different decision layers of the supply chain that are dictating the feasibility and optimality of the overall supply chain performance. Multi-level programming offers a holistic approach that explicitly accounts for this inherent hierarchy and interconnectivity between supply chain elements, however, requires more rigorous solution strategies as they are strongly NP-hard. In this work, we use the DOMINO framework, a data-driven optimization algorithm initially developed to solve single-leader single-follower bi-level mixed-integer optimization problems, and further develop it to address integrated planning and scheduling formulations with multiple follower lower-level problems, which has not received extensive attention in the open literature. By sampling for the production targets over a pre-specified planning horizon, DOMINO deterministically solves the scheduling problem at each planning period per sample, while accounting for the total cost of planning, inventories, and demand satisfaction. This input-output data is then passed onto a data-driven optimizer to recover a guaranteed feasible, near-optimal solution to the integrated planning and scheduling problem. We show the applicability of the proposed approach for the solution of a two-product planning and scheduling case study.


Type I interferon is required for T helper (Th) 2 induction by dendritic cells.
Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. However, the precise mechanisms involved in T helper (Th) 2 polarization by dendritic cells (DCs) are currently unclear. We have identified a previously unrecognized role for type I IFN (IFN-I) in enabling this process. An IFN-I signature was evident in DCs responding to the helminth Schistosoma mansoni or the allergen house dust mite (HDM). Further, IFN-I signaling was required for optimal DC phenotypic activation in response to helminth antigen (Ag), and efficient migration to, and localization with, T cells in the draining lymph node (dLN). Importantly, DCs generated from Ifnar1-/- mice were incapable of initiating Th2 responses in vivo These data demonstrate for the first time that the influence of IFN-I is not limited to antiviral or bacterial settings but also has a central role to play in DC initiation of Th2 responses.


[The nuclear translocation of circRNA CPSF6 promotes apoptosis of trophoblast cells induced by homocysteine].
Objective To investigate the role of circular RNA cleavage and polyadenylation specificity factor 6 (circRNA CPSF6) in the apoptosis of trophoblast cells induced by homocysteine (Hcy) and its mechanism. Methods HTR-8/SVneo human chorionic trophoblast cells were cultured in vitro and divided into control group (0 mmol/L Hcy treatment) and 1 mmol/L Hcy treatment group. Immunofluorescence cytochemical staining was used to detect the expression of caspase-3 in trophoblasts, and Western blot analysis was used to detect the caspase-3 protein level. The mRNA expression level of circRNA CPSF6 was detected by real-time quantitative PCR. Small interfering RNA (siRNA) was used to knock down the expression of circRNA CPSF6 in trophoblast cells. The expressions of caspase-3, caspase-9, Bcl2, and BAX were detected by Western blot analysis. Real-time quantitative PCR was used to detect the expression level of circRNA CPSF6 in the cytoplasm/nucleus of trophoblast cells before and after Hcy treatment. Results Compared with those in the control group, the expressions of caspase-3 and circRNA CPSF6 mRNA in the Hcy treatment group significantly increased. After knocking down circRNA CPSF6, the expression of caspase-3 decreased, and the mitochondrial apoptosis pathway was inhibited. In normal cultured trophoblast cells, circRNA CPSF6 was expressed in large amounts in the cytoplasm, and after Hcy treatment, circRNA CPSF6 was mainly expressed in the nucleus. Conclusion The mitochondrial apoptotic pathway is activated by circRNA CPSF6 nuclear translocation to promote trophoblast apoptosis induced by Hcy.


Nuclear antigens and antinuclear antibodies-their role in joint inflammation.
Nuclear antigens, including native DNA, denatured single-stranded DNA and soluble nucleoprotein are found in synovial effusions from a majority of all types of inflammatory joint disease. On the other hand, antinuclear antibodies are rarely detected in joint fluids, except in rheumatoid arthritis. Evidence that nucleoprotein and DNA immune complexes contribute to rheumatoid joint inflammation is reviewed.


[Role of endo-osseus implant in odonto-oral rehabilitation].
Dental implants have critically changed the restorative procedures available to edentulous patients. Biocompatible materials, precise surgical techniques and improved instrumentation give well trained practicioners various opportunities to achieve successful treatments. The necessity of combining full expertise in surgery and rational prosthetic planning with comprehensive occlusal management is emphasized. Recent advances in periodontal treatment of osseous and soft tissue defects, new grafting techniques and surgical approaches have dramatically enlarged the scope of oral implantology.


Consensus statement on ehrlichial disease of small animals from the infectious disease study group of the ACVIM. American College of Veterinary Internal Medicine.
Within the past several decades, the number of Ehrlichia spp. recognized to infect cats, dogs, and human beings has expanded substantially. The recent application of advanced techniques in molecular biology has changed how ehrlichiosis is diagnosed and has provided new tools for the assessment of treatment. As these techniques are applied, the numerous questions that relate to the management of dogs and cats with ehrlichiosis ultimately will be answered. We hope this consensus statement will assist veterinarians in the management of their patients.


Hyperpigmentation after nonsurgical blepharoplasty using plasma technology.
Nitrogen plasma is considered nowadays one of the efficient treatment options for nonsurgical blepharoplasty. Although it is an overall safe treatment, it has some side effects. This short paper addresses the risk of hyperpigmentation following the use of plasma and list few suggestions on how to prevent it.


Thymoquinone as a natural spermostatic substance in reproductive medicine: An experimental study.
Nonoxynol-9 a nonionic surfactant is widely used for its spermicidal effects. Finding new sperm immobilizing agents is necessary because Nonoxynol-9 damages the tissues of female reproductive system. The aim of this study was to evaluate the effects of Thymoquinone (TQ) as a potential spermostatic compound on the motility and viability of human spermatozoa. In this experimental study, the effects of 5, 10, 20, 50, 100 µg/ml, 1 and 10 mg/ml of TQ on normozoospermic semen samples were investigated. Sperm motility and viability were compared between untreated and TQ-treated aliquots of each semen sample. To evaluate the effects of TQ on the alteration of mitochondrial membrane potential (MMP), 32 semen samples were examined using 50 µg/ml of TQ. Flow cytometric analysis was performed after staining of spermatozoa with JC-1. Doses above 20 µg/ml of TQ could eventually immobilize all spermatozoa in culture medium. Adding 50 µg/ml of TQ did not significantly diminish the percentage of viable spermatozoa and flow cytometry results revealed that this amount of TQ could decrease sperm MMP. TQ could discontinue the movement of sperm cells in medium without reducing the population of live spermatozoa. It is more likely that TQ exerts its spermostatic action by mitigating the MMP of spermatozoa. Therefore, TQ could be considered as a potential new natural spermostatic chemical.


The influence of cognitive rehabilitation on cognitive competence in patients with Alzheimer's disease.
The development of dementia in Alzheimer's disease is known to be influenced by various factors. The research was carried out on 16 patients with a probable diagnosis of Alzheimer's disease (AD), who were first evaluated with MMSE. The patients were then divided according to gender, age, and the progress of the illness into two equal groups. The first group of patients was assigned an additional cognitive therapy for improving cognitive abilities alongside regular treatment while the second group was assigned only regular treatment. After 6 months the patients were re-evaluated using MMSE. The results show a statistically significant difference in cognitive abilities between the two groups with regard to the pre-therapy results. The results of the research are consistent with the results of other researches which imply a slower decrease in cognitive abilities in AD patients who are mentally active.


Circulating Osteocalcin Fractions are Associated with Vascular Calcification and Mortality in Chronic Hemodialysis Patients.
Vascular calcification, a component of chronic kidney disease-mineral and bone disorder (CKD-MBD), is prevalent in patients with end-stage kidney disease (ESKD) and contributes to high mortality. However, the association between the blood level of total osteocalcin (OC) and vascular calcification and mortality remains inconclusive. We, therefore, investigated whether different OC fractions can serve as biomarkers of vascular calcification and mortality in the ESKD population. This observational cohort study enrolled patients on maintenance hemodialysis. Plasma carboxylated OC (cOC), uncarboxylated OC (ucOC), and intact parathyroid hormone (PTH) were measured. The percentage of carboxylated OC (%cOC) was calculated as dividing cOC by total OC. The vascular calcification severity was defined by an aortic calcification grade. The patients were followed for three years and one month. A total of 184 patients were enrolled. In the multivariable logistic regression, plasma %cOC, but not cOC or ucOC, was independently associated with the severity of vascular calcification (OR 1.019, p = 0.036). A significant U-shaped correlation was found between plasma %cOC and PTH (p = 0.002). In the multivariable Cox regression, patients with higher plasma %cOC had a higher risk of mortality (quartiles Q4 versus Q1-Q3, HR 1.991 [95% CI: 1.036-3.824], p = 0.039). In patients undergoing chronic hemodialysis, plasma %cOC positively correlated with vascular calcification and exhibited a U-shaped correlation with PTH. Furthermore, a higher plasma %cOC was associated with increased mortality. These findings suggest that plasma %cOC may serve as a biomarker for CKD-MBD and a predictor of clinical outcomes in chronic hemodialysis patients.


Cytokines and apoptosis in atopic dermatitis.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. AD affects 10-20% of children worldwide and persists into adulthood in a minority of cases, affecting approximately 2-3% of the adult population, with an increased prevalence over the past decades in developed countries. Atopy is a genetic tendency to overproduce IgE class antibodies in response to common antigens found in the environment. Concurrence of different atopy such as allergic rhinitis or asthma in children with AD is estimated at 80%. AD is characterized by a vicious cycle of an allergic immune response. The emerging picture of the AD is a complex disorder with barrier dysfunction, immunological, genetic and environmental factors all playing key roles. Patients with severe or persistent disease and their families experience significant impairment in their quality of life, and in addition, AD places a heavy economic burden on society as a whole. Pathogenesis, the role of the epidermal barrier, mechanisms of cells apoptosis, the role of T cells and cytokines in AD are discussed in this article.


Random-effects meta-analysis for systematic reviews of phase I clinical trials: Rare events and missing data.
Phase I trials aim to establish appropriate clinical and statistical parameters to guide future clinical trials. With individual trials typically underpowered, systematic reviews and meta-analysis are desired to assess the totality of evidence. A high percentage of zero or missing outcomes often complicate such efforts. We use a systematic review of pediatric phase I oncology trials as an example and illustrate the utility of advanced Bayesian analysis. Standard random-effects methods rely on the exchangeability of individual trial effects, typically assuming that a common normal distribution sufficiently describes random variation among the trial level effects. Summary statistics of individual trial data may become undefined with zero counts, and this assumption may not be readily examined. We conduct Bayesian semi-parametric analysis with a Dirichlet process prior and examine the assumption. The Bayesian semi-parametric analysis is also useful for visually summarizing individual trial data. It provides alternative statistics that are computed free of distributional assumptions about the shape of the population of trial level effects. Outcomes are rarely entirely missing in clinical trials. We utilize available information and conduct Bayesian incomplete data analysis. The advanced Bayesian analyses, although illustrated with the specific example, are generally applicable. © 2016 The Authors. Research Synthesis Methods Published by John Wiley & Sons Ltd.


New markers for tracking endoderm induction and hepatocyte differentiation from human pluripotent stem cells.
The efficient generation of hepatocytes from human pluripotent stem cells (hPSCs) requires the induction of a proper endoderm population, broadly characterized by the expression of the cell surface marker CXCR4. Strategies to identify and isolate endoderm subpopulations predisposed to the liver fate do not exist. In this study, we generated mouse monoclonal antibodies against human embryonic stem cell-derived definitive endoderm with the goal of identifying cell surface markers that can be used to track the development of this germ layer and its specification to a hepatic fate. Through this approach, we identified two endoderm-specific antibodies, HDE1 and HDE2, which stain different stages of endoderm development and distinct derivative cell types. HDE1 marks a definitive endoderm population with high hepatic potential, whereas staining of HDE2 tracks with developing hepatocyte progenitors and hepatocytes. When used in combination, the staining patterns of these antibodies enable one to optimize endoderm induction and hepatic specification from any hPSC line.


Smartphone and social network addiction in early adolescents: The role of self-regulatory self-efficacy in a pilot school-based intervention.
Youths' online problematic behaviors, such as smartphone or social network sites (SNS) addiction, gained increasing attention nowadays, due to their impact on concurrent and later adjustment, such as emotional and/or behavioral problems, academic impairments, or relational issues. This study aims to evaluate the effectiveness of a pilot school-based intervention to contrast online addictive behaviors while fostering adolescents' self-regulative abilities. The intervention started in January 2022 in an Italian junior high school located in Rome, and consisted of four meetings with students. A total sample of 462 15-year-old adolescents (Mage = 15.2; SD = 0.50; 41% females; Ncontrol = 214; Nintervention = 248) was considered. Within the latent difference score framework, we examined short-term changes from the pre-to-the-postintervention levels of SNS and smartphone addiction, and self-regulatory self-efficacy (SRSE) beliefs as a possible booster of the intervention's effectiveness. Results showed a significant decrease in both online addictions (SNS and smartphone addiction), controlling for age, gender, sexual orientation, and socioeconomic status, because of the short-term efficacy of the project. The buffering effect of SRSE beliefs was further supported. These findings emphasized the usefulness of promoting youths' self-regulative beliefs to contrast problematic tendencies, according to a Positive Youth Development perspective which focused on resources rather than only on the prevention of negative outcomes for youths' adjustment.


High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients.
Mantle cell lymphoma (MCL) has a dismal outcome when treated with conventional chemotherapy. This single arm phase 2 study evaluated intensive consolidation treatment of patients with newly diagnosed MCL up to the age of 65 years, responsive to R-CHOP (rituximab, cyclophosphamide, oncovin, adriamycin, prednisolone). Endpoints for evaluation were toxicity, failure-free survival (FFS) and overall survival (OS). Eighty-seven patients were treated with three cycles of R-CHOP. Sixty-six patients responded to R-CHOP with at least a partial response, 62 continued protocol treatment with high-dose cytarabine (Ara-C; 2000 mg/m(2), bid. over 4 d) and 61 patients received rituximab and stem cell harvest, followed by BEAM (carmustine, etoposide, Ara-C, melphalan) and autologous stem cell rescue. Non-haematological toxicity, grades III and IV, was seen in 8% of the patients after R-CHOP, in 22% after high-dose Ara-C and in 55% after BEAM. The overall response rate was 70% (complete response rate 64%, partial response rate 6%), FFS and OS at 4 years were 36 +/- 7% and 66 +/- 6%, respectively. The FFS and OS at 4 years from the evaluation after BEAM in the 61 R-CHOP responsive patients was 46 +/- 9% and 79 +/- 7%, respectively. In conclusion, high-dose Ara-C and BEAM with stem cell rescue in newly diagnosed MCL patients responsive to R-CHOP is a manageable treatment with respect to toxicity. This regimen leads to long-term, but probably not durable, remissions.


Sonography of acute appendicitis in children: 7 years experience.
The objective of this prospective study was to determine the accuracy in diagnosing appendicitis in children by using high-resolution graded compression sonography. During a 7-year period, 3859 children (mean age 9.9 years) with clinically suspected appendicitis were evaluated by sonography with the graded compression technique. The ultrasound results were correlated with the intraoperative and histopathological findings or clinical outcome. High-resolution sonography was performed in 3859 children. Of the 610 patients who underwent a laparotomy, 494 had histologically proven acute or perforated appendicitis (prevalence 13%). In these children, sensitivity, specificity and overall accuracy of sonography were 90%, 97% and 96%, respectively. The reasons for false-negative and false-positive results are discussed. Although the use of ultrasound to diagnose acute appendicitis in children has excellent results, the decision for surgery remains a clinical one because of the continuing false-negative and false-positive results from sonography.


Gait characteristics during crossing over obstacle in patients with glaucoma using insole foot pressure.
Glaucoma, is the most common cause of irreversible visual deficits, presents as an injury to the optic nerve and it is mainly associated with elevated intraocular pressure. The main symptom of glaucoma is a reduction of the visual field, which is usually a source of complaint at the advanced stage of disease. Because of visual deficit, gait dysfunctions, including low gait speed and increased bumping into objects, postural sway, and falling are occurred. Many studies have used stopwatch or motion-sensing devices to report on gait function following glaucoma. However, there are few reports on gait dysfunction assessed by examining foot pressure. This study investigated gait ability following glaucoma according to different gait conditions by assessing foot pressure. Thirty older adults (15 in the sex- and age-matched normal group and 15 in the glaucoma group) were recruited for this study. All participants were walked under 2 different gait conditions in an F-scan system and the subject' assessments were randomly assigned to rule out the order effect. Conditions included: gait over an obstacle in a straight 6 m path, gait in a straight path without an obstacle in the 6 m path. Gait variables included cadence, gait cycle, stance time, center of force (COF) deviation, and COF excursion. About 10 minutes were taken for gait evaluation. When walking without an obstacle on a 6 m path, there were significant differences between the 2 groups in gait speed, cadence, gait cycle, and stance time (P < .05). There were significant differences when walking with an obstacle on a 6 m path (P < .05). Two-way analysis of variance showed significant effects associated with "glaucoma" not gait condition on all outcomes except for COF deviation and excursion. Also, there was no the interaction effect between "glaucoma" and "gait condition." We demonstrated that glaucoma patients selected the gait strategy such as lower gait function in both gait conditions particularly, slower gait speed and cadence and longer gait cycle and stance time, as determined by examining foot pressure. We believe that our results could help to improve the quality of life of patients with glaucoma.


Can money heal all wounds? Social exchange norm modulates the preference for monetary versus social compensation.
Compensation is a kind of pro-social behavior that can restore a social relationship jeopardized by interpersonal transgression. The effectiveness of a certain compensation strategy (e.g., repaying money, sharing loss, etc.) may vary as a function of the social norm/relationship. Previous studies have shown that two types of norms (or relationships), monetary/exchange and social/communal, differentially characterize people's appraisal of and response to social exchanges. In this study, we investigated how individual differences in preference for these norms affect individuals' perception of others' as well as the selection of their own reciprocal behaviors. In a two-phase experiment with interpersonal transgression, we asked the participant to perform a dot-estimation task with two partners who occasionally and unintentionally inflicted noise stimulation upon the participant (first phase). As compensation one partner gave money to the participant 80% of the time (the monetary partner) and the other bore the noise for the participant 80% of the time (the social partner). Results showed that the individuals' preference for compensation (repaying money versus bearing noise) affected their relationship (exchange versus communal) with the partners adopting different compensation strategies: participants tended to form communal relationships and felt closer to the partner whose compensation strategy matched their own preference. The participants could be differentiated into a social group, who tended to form communal relationship with the social partner, and a monetary group, who tended to form communal relationship with the monetary partner. In the second phase of the experiment, when the participants became transgressors and were asked to compensate for their transgression with money, the social group offered more compensation to the social partners than to the monetary partners, while the monetary group compensated less than the social group in general and showed no difference in their offers to the monetary and social partners. These findings demonstrate that the effectiveness of compensation varies as a function of individuals' preference for communal versus monetary norm and that monetary compensation alone does not heal all wounds.


Fenestrated endovascular repair of abdominal aortic aneurysms is associated with increased morbidity but comparable mortality with infrarenal endovascular aneurysm repair.
A recent prospective study found that fenestrated endovascular abdominal aortic aneurysm (AAA) repair (FEVAR) was safe and effective in appropriately selected patients at experienced centers. As this new technology is disseminated to the community, it will be important to understand how this technology compares with standard endovascular AAA repair (EVAR). The goal of this study was to compare the outcomes of FEVAR vs EVAR of AAAs. The American College of Surgeons-National Surgical Quality Improvement Program database from 2005 to 2012 was queried for AAAs (International Classification of Diseases, Ninth Revision code 441.4). Patients were stratified according to procedure (FEVAR vs EVAR). A bivariate analysis was done to assess preoperative and intraoperative risk factors for postoperative outcomes. Thirty-day postoperative mortality and complication rates were described for each procedure type. Multivariable logistic regression was performed to assess the association between the type of procedure and the risk of postoperative complications. A total of 458 patients underwent FEVAR and 19,060 patients underwent EVAR for AAA. Patients undergoing FEVAR were older (P = .02) and less likely to have a bleeding disorder (P = .046). Otherwise, the incidence of comorbidities in both groups was similar. FEVAR was associated with increased median operative time (156 vs 137 minutes; P < .001), and average postoperative length of stay (3.3 vs 2.8 days; P = .03). There was a statistically significant increase in overall complications (23.6% vs 14.3%; P < .001) and postoperative transfusions (15.3% vs 6.1%, P < .001) and trends toward increased cardiac complications (2.2% vs 1.3%; P = .09) and the need for dialysis (1.5% vs 0.8%; P = .08) in the FEVAR group. Mortality (2.4% vs 1.5%; P = .12) was not statistically different. On multivariable analysis, FEVAR remained independently associated with the need for postoperative transfusions when operative time was <75th percentile (adjusted odds ratio, 1.72; 95% confidence interval, 1.09-2.72; P = .02) as well as when operative time was >75th percentile for respective procedures (adjusted odds ratio, 5.33; 95% confidence interval, 3.55-8.00; P < .001). Patients undergoing FEVAR are more likely than patients undergoing EVAR to receive blood transfusions postoperatively and are more likely to sustain postoperative complications. Although mortality was similar, trends toward increased cardiac and renal complications may suggest the need for judicious dissemination of this new technology. Future research with larger number of FEVAR cases will be necessary to determine if these associations remain.


[Diagnosis and minimally invasive treatment of gastric remnant cancer].
Gastric remnant cancer (GRC) is defined as cancer in the remnant stomach after partial gastrectomy. The incidence of GRC is rising in recent years. The carcinogenesis, development, and metastasis of GRC are different from primary gastric cancer. The early detection of GRC should be based on rational surveillance of patients following gastrectomy. For early stage GRC, endoscopic resection is one of the safe and effective methods. For advanced GRC, the primary treatment alternative is surgical resection. Minimally invasive procedures such as laparoscopic exploration, laparoscopic-assisted resection of GRC are still safe choices for experienced surgeons.


Thermopriming-Induced Autophagy in Shoot Apical Meristem of Arabidopsis.
Since embryogenesis, plants deal with environmental changes, which might affect their growth and development. Plant autophagy has been shown to function in various stress responses, immunity, development, and senescence. Acquired thermotolerance or thermopriming is enhanced resistance to the elevated temperature following heat stress. Potential contribution of autophagy mechanism after thermopriming was investigated in shoot apical meristem (SAM) of Arabidopsis thaliana. Transcriptic expression of Autophagy related Genes (ATGs) were analyzed by qRT-PCR data in 5-day old Arabidopsis thaliana (Col0) seedlings at 4 h and 24 h after thermopriming. Autophagy induction was confirmed by confocal microscopy. Expression patterns of 39 ATGs and ATG-receptors were described and relevant thermopriming induced autophagy genes were identified according to their highest expression fold changes during the time after treatment. Significantly, ATG8A, ATG8B, ATG8G, ATG8H, ATI1, ATI2, NBR1, and TSPO genes were identified as the most relevant thermopriming-associated autophagy genes especially in SAM of young seedlings. This mainly implies the role of ATG8 core proteins and their receptor interactors in the regulation of autophagy in form of selective or non-selective during environmental stresses. Autophagy, a conserved mechanism for cell survival in plants will be activated in response to the thermopriming which is a promoted acquired resistance stimulus. Determined key genes and components of autophagy associated with thermal priming signaling pathway could be noteworthily employed to study transcriptional regulation of autophagy and integrated defense system against environmental stresses for the improvement of plant thermal tolerance and resistance to the pathogens.


The heterogeneity of the long-term course of schizophrenia.
Research has demonstrated considerable heterogeneity in the long-term course of schizophrenia. In the period preceding the onset of frank psychosis (onset), patients vary relative to the rapidity of onset, the presence or absence of associality, and the presence or absence of semipsychotic symptoms. Following the onset of psychosis (middle course), patients may suffer from episodic or unremitting psychosis, and may or may not exhibit the deficit syndrome. In late adult life (late course), patients vary relative to the presence or absence of an improvement in psychosis and social capability. The usual approach to the study of putative course subtypes is to define a subtype by a number of features; they may include features of more than one epoch. In addition, the course of psychosis has not been distinguished from enduring personality impairments in these subtypes. Another approach to defining putative course subtypes would be based on dichotomizing patients according to the presence or absence of a particular feature of a single epoch. This second approach has important advantages: the availability of larger study populations and a diminished liability for confounding due to the correlates of features other than those under scrutiny.


Repetition blindness has a perceptual locus: evidence from online processing of targets in RSVP streams.
Four experiments tested whether repetition blindness (RB; reduced accuracy reporting repetitions of briefly displayed items) is a perceptual or a memory-recall phenomenon. RB was measured in rapid serial visual presentation (RSVP) streams, with the task altered to reduce memory demands. In Experiment 1 only the number of targets (1 vs. 2) was reported, eliminating the need to remember target identities. Experiment 2 segregated repeated and nonrepeated targets into separate blocks to reduce bias against repeated targets. Experiments 3 and 4 required immediate "online" buttonpress responses to targets as they occurred. All 4 experiments showed very strong RB. Furthermore, the online response data showed clearly that the 2nd of the repeated targets is the one missed. The present results show that in the RSVP paradigm, RB occurs online during initial stimulus encoding and decision making. The authors argue that RB is indeed a perceptual phenomenon.


Relationship Between ACE2 and Other Components of the Renin-Angiotensin System.
Angiotensin-converting enzyme 2 (ACE2) is a key counter-regulatory component of the renin-angiotensin system. Here, we briefly review the mechanistic and target organ effects related to ACE2 activity, and the importance of ACE2 in SARS-CoV-2 infection. ACE2 converts angiotensin (Ang) II to Ang-(1-7), which directly opposes the vasoconstrictive, proinflammatory, and prothrombotic effects of Ang II. ACE2 also facilitates SARS-CoV-2 viral entry into host cells. Drugs that interact with the renin-angiotensin system may impact ACE2 expression and COVID-19 pathogenesis; however, the magnitude and direction of these effects are unknown at this time. High quality research is needed to improve our understanding of how agents that act on the renin-angiotensin system impact ACE2 and COVID-19-related disease outcomes.


TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients.
Inflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86).TNFR1/2 were significantly higher in patients with heart failure and diabetes mellitus based on mRNA expression to protein expression and serum expression. However, there were no differences in mRNA, protein, and serum levels of TNFR1/2 between the HF group and DM group. Furthermore, there were no differences between the groups in some traditional serum inflammatory markers.This study demonstrated higher expressions of TNFR, NF-kB, and JNK in patients with heart failure and diabetes mellitus. Compared with traditional serum markers, TNFR1 and TNFR2 are associated with heart failure risk in type 2 diabetes mellitus patients.


ShinyTPs: Curating Transformation Products from Text Mining Results.
Transformation product (TP) information is essential to accurately evaluate the hazards compounds pose to human health and the environment. However, information about TPs is often limited, and existing data is often not fully Findable, Accessible, Interoperable, and Reusable (FAIR). FAIRifying existing TP knowledge is a relatively easy path toward improving access to data for identification workflows and for machine-learning-based algorithms. ShinyTPs was developed to curate existing transformation information derived from text-mined data within the PubChem database. The application (available as an R package) visualizes the text-mined chemical names to facilitate the user validation of the automatically extracted reactions. ShinyTPs was applied to a case study using 436 tentatively identified compounds to prioritize TP retrieval. This resulted in the extraction of 645 reactions (associated with 496 compounds), of which 319 were not previously available in PubChem. The curated reactions were added to the PubChem Transformations library, which was used as a TP suspect list for identification of TPs using the open-source workflow patRoon. In total, 72 compounds from the library were tentatively identified, 18% of which were curated using ShinyTPs, showing that the app can help support TP identification in non-target analysis workflows.


The use of a radiolabelled saccharin solution to monitor the effect of the preservatives thiomersal, benzalkonium chloride and EDTA on human nasal clearance.
The effect of thiomersal, benzalkonium chloride and ethylenediaminetetraacetic acid (EDTA) on the nasal mucociliary clearance of healthy volunteers has been investigated using a modified saccharin test and gamma scintigraphy concomitantly. A significant correlation was found between the two techniques. Using each subject as his/her own control, none of the preservatives significantly altered the rate of clearance or proportion cleared from the nasal cavity after the administration of a single dose. This result is at variance with some in-vitro findings.


The incidence of methylphenidate use by Canadian children: what is the impact of socioeconomic status and urban or rural residence?
To examine socioeconomic, demographic, and behavioural factors that influence the incidence of methylphenidate use among children aged 4 to 13 years. A total of 11,316 children, aged 2 through 11 years, from Cycle 1 (1994-95) of the National Longitudinal Survey of Children and Youth were followed up 2 years later in Cycle 2 (1996-97). The outcome measure was methylphenidate use in Cycle 2. Individual-level explanatory variables included sex, age, socioeconomic status (SES), mother's age at birth of child, lone-parent family status, parental working status, and hyperactivity-impulsivity and inattention probabilities. Area-level explanatory variables included income and rural or urban residence. We used hierarchical linear modelling to examine individual- and area-level factors that predicted methylphenidate use. The strongest predictors of methylphenidate use were behavioural: children with high hyperactive-impulsive and (or) inattention behaviours in 1994, compared with children low on these behaviours, were 4.5 to 6 times more likely to use methylphenidate 2 years later. SES remained a significant predictor of the incidence of methylphenidate use, even when other significant predictors were held constant, with lower SES being associated with higher use. Area-level income also predicted methylphenidate use. Even when children with similar behavioural symptoms and demographic characteristics were compared, socioeconomic factors had a significant impact on incidence of methylphenidate use.


Variable judgments of decisional capacity in cognitively impaired research subjects.
To compare assessments of the decisional capacity of cognitively impaired patients by research assistants (RAs) and by family caregiver/proxies and to determine whether either or both groups judge capacity differently depending on the specific (hypothetical) research enrollment decision being made. Cross-sectional. Three clinics, one each in Ohio, Kentucky, and Illinois. One hundred forty-nine patients with established dementia diagnoses and their caregiver/proxies. As part of a longer interview, patients were asked about future enrollment in five hypothetical research projects with varying risks and benefits. After patients reported each decision and reasons for that decision, RAs (using Applebaum and Grisso's four standards) indicated whether the patients were competent to make that decision on their own. In separate interviews, caregiver/proxies were asked for a similar appraisal based on life experience with the patient. RA and proxy judgments were compared. Capacity judgments by RAs and by caregiver/proxies differed according to specific project for most patients. Agreement between RA and caregiver/proxy judgments varied according to project, but agreement was only fair when tested using kappa (range in data 0.21-0.39). Caregiver/proxies appraised 50 patients as competent for all decisions, and RAs assessed 47 as so. Of these, only 24 were the same patients. If capacity were assessed anew for each enrollment decision, more potential participants could maintain authority in making those decisions.


Comment: why do nondopaminergic features in Parkinson disease matter?
Parkinson disease (PD) is a progressive multisystem disorder affecting both dopaminergic and nondopaminergic neurons. Whereas dopaminergic (mainly motor) symptoms are well-defined, the nondopaminergic symptoms (mainly nonmotor, such as depression, cognitive decline, anxiety, apathy, fatigue, sleep disorders, sensory symptoms, postural control deficits, orthostatic hypotension, and urogenital and gastrointestinal symptoms) are frequently missed or neglected during routine clinical visits; consequently, they are underinvestigated and undertreated. The neglect of nondopaminergic symptoms is surprising because i) they occur in almost all patients with PD throughout the course of the disease,(1) and can even precede the occurrence of the classic motor symptoms; ii) they affect almost all aspects of daily life; and iii) have a greater effect on health-related quality of life than dopaminergic symptoms.(2) During the last decade, several initiatives have addressed this deficit with specific assessment procedures for application in clinical practice and research.(1.)


Low Frequency Dielectric Relaxation and Conductance of Solid Polymer Electrolytes with PEO and Blends of PEO and PMMA.
Solid polymer electrolytes are mixtures of polymer and inorganic salt. There are quite a number of studies dealing with the relationship between electric conductivity and structural relaxation in solid polymer electrolytes. We present a phenomenological approach based on fluctuation-dissipation processes. Phase heterogeneity appears in poly(ethylene oxide) (PEO) of high molecular mass and its blends due to crystallization and accompanying phase segregation. Addition of salt hampers crystallization, causing dynamic heterogeneity of the salt mixtures. Conductivity is bound to amorphous phase; the conductivity mechanism does not depend on content of added salt. One observes dispersion of conductivity relaxation only at low frequency. This is also true for blends with poly(methyl methacrylate) (PMMA). In blends, the dynamics of relaxation depend on glass transition of the system. Glassy PMMA hampers relaxation at room temperature. Relaxation can only be observed when salt content is sufficiently high. As long as blends are in rubbery state at room temperature, they behave PEO-like. Blends turn into glassy state when PMMA is in excess. Decoupling of long-ranging and dielectric short-ranging relaxation can be observed. Conductivity mechanism in PEO, as well as in blends with PMMA were analyzed in terms of complex impedance Z*, complex permittivity, tangent loss spectra and complex conductivity.


Can the response to Omalizumab be influenced by treatment duration? A real-life study.
It is unknown whether Omalizumab effectiveness changes over the course of time. Our retrospective real-life study tried to analyze whether Omalizumab response may be influenced by treatment duration. 340 severe asthmatics treated with Omalizumab for different periods of time were recruited. They were subdivided into 4 groups according to the Omalizumab treatment length: <12, between 12 and 24, between 24 and 60 and >60 months. Omalizumab treatment results (FEV1, exacerbations, ACT, SABA use, asthma control levels, medications used e and ICS doses) were compared. ACT, exacerbations, GINA control levels, ICS doses and SABA use were similar in all groups with different Omalizumab treatment durations. Using a linear regression model, corrected for all confounding variables, a higher significant positive increase in FEV1% in subjects treated for 12-24 (β = 9.49; p = 0.034) or 24-60 months (β = 8.56; p = 0.043) was found when compared with subjects treated for a shorter period. Treatment duration was positively associated with a step down of the other associated therapies (OR: 1.013; p = 0.019). This association was more relevant (OR: 4.167; p = 0.005) when we considered Omalizumab treatment duration >60 months compared to the shorter therapy. In particular, the percentage of subjects that were taking Montelukast, LABAs and oral corticosteroids was lower in the group treated with Omalizumab for a longer period of time. In real-life, the positive Omalizumab response remained stable for over 60 months. Long term Omalizumab treatment may lead to a discontinuation of some associated medications and to a slowing down of FEV1 decline.


Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: a phase II pilot study.
The aim of the present trial was to investigate the protective effects on ovarian function, and the efficacy and tolerability of goserelin added to adjuvant chemotherapy for early breast cancer. Following surgical treatment, 64 premenopausal patients with early breast cancer received goserelin 3.6 mg (every 28 days for 1 year) and an adjuvant treatment which was chosen according to the patient's prognosis. Median age was 42 years (range 27-50). ECOG performance status was 0-1 in all patients. Twenty-eight patients (44%) had estrogen receptor (ER)+ tumors and 36 (56%) patients had ER- tumors. Fifty-two (81%) patients had stage II disease and 12 (19%) had stage III disease. Eighteen patients received cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, 46 patients received an anthracycline-based regimen, and nine of them received high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation. Fifty-one patients (80%) were irradiated. ER+ patients also received tamoxifen for 5 years. Serum estradiol was suppressed to values below 40 pg/ml in all patients. After a median follow-up of 55 months, 86% of patients had resumed normal menses, 84% of patients were disease-free and 94% were alive. The 1-, 3- and 5-year projected recurrence-free survival rates were 100, 81 and 75%, respectively. Five years after treatment one patient had a pregnancy that ended with a normal childbirth. No unexpected adverse events were reported. These data show that the addition of goserelin to adjuvant therapy of premenopausal patients with early breast cancer is well tolerated and protects long-term ovarian function.


Predictors of mortality among long-term care residents with SARS-CoV-2 infection.
While individuals living in long-term care (LTC) homes have experienced adverse outcomes of SARS-CoV-2 infection, few studies have examined a broad range of predictors of 30-day mortality in this population. We studied residents living in LTC homes in Ontario, Canada, who underwent PCR testing for SARS-CoV-2 infection from January 1 to August 31, 2020, and examined predictors of all-cause death within 30 days after a positive test for SARS-CoV-2. We examined a broad range of risk factor categories including demographics, comorbidities, functional status, laboratory tests, and characteristics of the LTC facility and surrounding community were examined. In total, 304 potential predictors were evaluated for their association with mortality using machine learning (Random Forest). A total of 64,733 residents of LTC, median age 86 (78, 91) years (31.8% men), underwent SARS-CoV-2 testing, of whom 5029 (7.8%) tested positive. Thirty-day mortality rates were 28.7% (1442 deaths) after a positive test. Of 59,702 residents who tested negative, 2652 (4.4%) died within 30 days of testing. Predictors of mortality after SARS-CoV-2 infection included age, functional status (e.g., activity of daily living score and pressure ulcer risk), male sex, undernutrition, dehydration risk, prior hospital contacts for respiratory illness, and duration of comorbidities (e.g., heart failure, COPD). Lower GFR, hemoglobin concentration, lymphocyte count, and serum albumin were associated with higher mortality. After combining all covariates to generate a risk index, mortality rate in the highest risk quartile was 48.3% compared with 7% in the first quartile (odds ratio 12.42, 95%CI: 6.67, 22.80, p < 0.001). Deaths continued to increase rapidly for 15 days after the positive test. LTC residents, particularly those with reduced functional status, comorbidities, and abnormalities on routine laboratory tests, are at high risk for mortality after SARS-CoV-2 infection. Recognizing high-risk residents in LTC may enhance institution of appropriate preventative measures.


Bubble gating in biological ion channels: A density functional theory study.
We study the behavior of a waterlike liquid inside the gate of a biological ion channel following the basic geometry of the well studied potassium channel KcsA. We calculate the three-dimensional density distribution ρ(r) of the liquid within the framework of classical density functional theory and observe the formation of a low density region (bubble) when the gate is narrow. This observation corresponds to a finite-size form of capillary evaporation and supports the so-called bubble-gate theory. From the density profile we also compute the energy landscape of the gate and the energy required to change the gate from a closed (narrow) to an open (wide) state and vice versa.


Relational aggression, victimization, and adjustment during middle childhood.
A secondary analysis of the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development was conducted to test the mechanisms by which relational aggression in third grade was associated both directly and indirectly with relational victimization in sixth grade. A large sample (N = 1,035; 522 girls; M = 8.3 years old; SD = 0.23) and multiple informants (teacher, child, and parent report) and methods were used to test several theoretically driven hypotheses. Our path analysis model suggested evidence for both direct and indirect pathways consistent with the sequential social process model of peer harassment. Relational aggression was significantly associated with future relational victimization even after controlling for physical aggression and gender. Loneliness mediated the direct association between relational aggression and peer victimization. A second model testing the reverse direction of effect revealed that relational victimization in third grade predicted relational aggression in sixth grade and was associated with loneliness and depressive symptoms in fifth grade, but there was no evidence for any of the indirect pathways.


Lymphography as a guide during laparotomy in Hodgkin's and non-Hodgkin's lymphomas.
Lymphography of 123 newly diagnosed patients with lymphoma was followed by staging laparotomy without intra-operative abdominal roentgenography. These patients were retrospectively evaluated for residual abnormal nodes with postoperative abdominal roentgenography. Sixteen patients with pathologically normal nodes at laparotomy had residual lymphographically abnormal nodes at postoperative roentgenography. Nine patients received less extensive irradiation than they would have if the remaining abnormal nodes had been biopsied and found to contain tumor. Two had shortened survivals as an apparent consequence.


Prey density and the behavioral flexibility of a marine predator: the common murre (Uria aalge).
Flexible time budgets allow individual animals to buffer the effects of variable food availability by allocating more time to foraging when food density decreases. This trait should be especially important for marine predators that forage on patchy and ephemeral food resources. We examined flexible time allocation by a long-lived marine predator, the Common Murre (Uria aalge), using data collected in a five-year study at three colonies in Alaska (USA) with contrasting environmental conditions. Annual hydroacoustic surveys revealed an order-of-magnitude variation in food density among the 15 colony-years of study. We used data on parental time budgets and local prey density to test predictions from two hypotheses: Hypothesis A, the colony attendance of seabirds varies nonlinearly with food density; and Hypothesis B, flexible time allocation of parent murres buffers chicks against variable food availability. Hypothesis A was supported; colony attendance by murres was positively correlated with food over a limited range of poor-to-moderate food densities, but independent of food over a broader range of higher densities. This is the first empirical evidence for a nonlinear response of a marine predator's time budget to changes in prey density. Predictions from Hypothesis B were largely supported: (1) chick-feeding rates were fairly constant over a wide range of densities and only dropped below 3.5 meals per day at the low end of prey density, and (2) there was a nonlinear relationship between chick-feeding rates and time spent at the colony, with chick-feeding rates only declining after time at the colony by the nonbrooding parent was reduced to a minimum. The ability of parents to adjust their foraging time by more than 2 h/d explains why they were able to maintain chick-feeding rates of more than 3.5 meals/d across a 10-fold range in local food density.


"Happy feet": evaluating the benefits of a 100-day 10,000 step challenge on mental health and wellbeing.
An increased awareness of the health benefits of walking has emerged with the development and refinement of accelerometer equipment. Evidence is beginning to highlight the value of promoting walking, particularly focusing on the Japanese mark of obtaining 10,000 steps per day. Workplace based step challenges have become popular to engage large cohorts in increasing their daily physical activity in a sustainable and enjoyable way. Findings are now highlighting the positive health effects of these medium-term programs (typically conducted over a few months) in terms of cardiovascular health, reducing diabetes risk and improving lifestyle factors such as weight and blood pressure. As yet, research has not focused on whether similar improvements in psychological health and wellbeing are present. This study investigated the impact of a 100-day, 10,000 step program on signs of depression, anxiety and stress as well as general wellbeing using standardised psychological scales. The results indicated a small but consistent effect on all of these measures of mental health over the term of the program. This effect appeared irrespective of whether a person reached the 10,000 step mark. These results highlight improved mental health and wellbeing in people undertaking this 100-day 10,000 step program and indicates the efficacy and potential of these programs for a modest, yet important improvement in mental health. Notably, targets reached may be less important than participation itself.


Problems with multiple use of transfer buffer in protein electrophoretic transfer.
Two-dimensional gel electrophoresis (2DE) and SDS-PAGE are the two most useful methods in protein separation. Proteins separated by 2DE or SDS-PAGE are usually transferred to membranes using a variety of methods, such as electrophoretic transfer, heat-mediated transfer, or nonelectrophoretic transfer, for specific protein detection and/or analysis. In a recent study, Pettegrew et al. claim to reuse transfer buffer containing methanol for at least five times for transferring proteins from SDS-PAGE to polyvinylidene difluoride. They add 150-200 ml fresh transfer solution each time for extended use as a result of loss of transfer buffer. Finally, they test efficiency of each protein transfer by chemiluminescence detection. Here, we comment on this report, as we believe this method is not accurate and useful for protein analysis, and it can cause background binding as well as inaccurate protein analysis.


Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis.
Additional chromosomal abnormalities (ACAs) in Philadelphia-positive cells have been reported in ∼ 5% of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). Few studies addressing the prognostic significance of baseline ACAs in patients treated with imatinib have been published previously. The European LeukemiaNet recommendations suggest that the presence of ACAs at diagnosis is a "warning" for patients in early CP, but there is not much information about their outcome after therapy with tyrosine kinase inhibitors. To investigate the role of ACAs in early CP CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective trials of the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on CML: 378 patients were evaluable and ACAs occurred in 21 patients (5.6%). The overall cytogenetic and molecular response rates were significantly lower and the time to response was significantly longer in patients with ACAs. The long-term outcome of patients with ACAs was inferior, but the differences were not significant. The prognostic significance of each specific cytogenetic abnormality was not assessable. Therefore, we confirm that ACAs constitute an adverse prognostic factor in CML patients treated with imatinib as frontline therapy.


[Relationship of body mass index with cancer detection in prostate biopsy].
To investigate the relationship of body mass index with cancer detection on prostate biopsy. A total of 168 patients undergoing a prostate biopsy were divided into obese and non-obese groups by BMI ≥ 25 or < 25. Then the differences of prostate-specific antigen (PSA) level, prostate volume, prostate cancer detection rate and pathology result between two groups. The obese group had a higher rate of cancer detection than the non-obese group [67.1% (51/76) vs 48.9% (45/92), P < 0.05]. Logistics regression analysis showed that BMI ≥ 25 had a positive correlation with cancer detection on biopsy. Body mass index can raise the risk of prostate cancer on biopsy.


Complete Genome Sequence of Starkeya sp. Strain ORNL1, a Soil Alphaproteobacterium Isolated from the Rhizosphere of Populus deltoides.
Starkeya sp. strain ORNL1 is an alphaproteobacterium isolated from the rhizosphere of an Eastern cottonwood tree. Starkeya spp. are physiologically versatile, using a wide range of nutritional and energetic resources and serving important ecological roles in carbon and sulfur cycling. The 6.3-Mb chromosome of Starkeya sp. strain ORNL1 was completely sequenced and will help in understanding nutrient cycles.


Phase II study of ifosfamide and etoposide chemotherapy for extensive-disease small-cell lung cancer.
We conducted a phase II study of ifosfamide and etoposide chemotherapy in patients with untreated extensive-disease small-cell lung cancer to assess response and toxicity. Between January 1994 and December 1995, 16 patients were treated. Ifosfamide and etoposide doses were ifosfamide 2 g/m2, with mesna, i.v. infusion over 30 minutes on days 1-3 and etoposide 80 mg/m2 i.v. over 120 minutes on days 1-3 every 4 weeks for up to six cycles. All patients were evaluable for toxicity profile and treatment response. As expected, the major toxicity was myelosuppression. With one exception, grade 3 or 4 leukopenia occurred in all patients during treatment, and 48.7% of the total courses had grade 3 or 4 leukopenia. Nine of 16 patients (56.3%) experienced episodes of febrile neutropenia. One toxic death due to febrile neutropenia with sepsis was documented. Toxicities other than leukopenia were few and mild in severity. After two cycles of treatment, the overall response rate was 81.3% (95% confidence interval 62.2-100) in this study. The median duration of response was 8 months and median survival was 11 months. In conclusion, ifosfamide and etoposide is an active combination regimen with acceptable toxicity profile in Chinese patients with extensive-disease small-cell lung cancer.


Proteome profiling of early seed development in Cunninghamia lanceolata (Lamb.) Hook.
Knowledge of the proteome of the early gymnosperm embryo could provide important information for optimizing plant cloning procedures and for establishing platforms for research into plant development/regulation and in vitro transgenic studies. Compared with angiosperms, it is more difficult to induce somatic embryogenesis in gymnosperms; success in this endeavour could be increased, however, if proteomic information was available on the complex, dynamic, and multistage processes of gymnosperm embryogenesis in vivo. A proteomic analysis of Chinese fir seeds in six developmental stages was carried out during early embryogenesis. Proteins were extracted from seeds dissected from immature cones and separated by two-dimensional difference gel electrophoresis. Analysis with DeCyder 6.5 software revealed 136 spots that differed in kinetics of appearance. Analysis by liquid chromatography coupled to tandem mass spectrometry and MALDI-TOF mass spectrometry identified proteins represented by 71 of the spots. Functional annotation of these seed proteins revealed their involvement in programmed cell death and chromatin modification, indicating that the proteins may play a central role in determining the number of zygotic embryos generated and controlling embryo patterning and shape remodelling. The analysis also revealed other proteins involved in carbon metabolism, methionine metabolism, energy production, protein storage, synthesis and stabilization, disease/defence, the cytoskeleton, and embryo development. The comprehensive protein expression profiles generated by our study provide new insights into the complex developmental processes in the seeds of the Chinese fir.


Adipose tissue as a key player in obstructive sleep apnoea.
Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.


[ST elevation during ergometric test: correlation with coronary angiography].
ST elevation during ergometric stress test (EST) is relatively rare. Its prevalence depends upon the tested population but occurs more frequently in patients who have had myocardial infarction or variant angina. This phenomenon is very rare in patients with typical exertional angina and its pathogenesis is still unclear. We studied a group of 75 consecutive patients with exertional angina who underwent EST and coronary angiography. A symptom limited EST was performed in the upright position on a cycloergometer with load increases of 25 watts every 3 minutes and 12 leads were monitored during all test. Coronary angiography was performed according to Judkins technique. From these patients, according to Froelicher's criteria, a group of 49 patients (age 32-68, mean 51.6 years), without myocardial infarction and/or left ventricular asynergy, was selected. All patients had a coronary artery disease (16 patients with 3 vessels, 11 patients with 2 vessels and 22 patients with 1 vessel disease). The EST was positive for ST depression in 31 patients (63.3%) and for ST elevation in 5 patients (10.1%), while 13 patients (26.6%) had a non diagnostic EST. The ST elevation occurs in V1-V2 and it was associated in all cases with a stenosis in the left anterior descending (LAD) artery. Therefore we divided the 19 patients with LAD stenosis into two subgroups: subgroups A (9 patients, mean age 49.6 years) with LAD stenosis > or = 90% and subgroups B with LAD stenosis between 70% and 90%. ST elevation occurs in 5 patients (55.5%) of subgroup A and in no patient of the subgroup B. Moreover, in the subgroup A ST elevation seems to be related to the anatomic localization of the stenosis: in fact it appears in 83.3% of patients with LAD stenosis located before the onset of the first diagonal branch. From these data it can be desumed that ST elevation in V1-V2 that occurs in patients with exertional angina and without myocardial infarction or variant angina is strongly predictive of a very important LAD stenosis.


Role of beta 2 integrins in the recruitment of phagocytic cells in joint inflammation in the rat.
Adhesion molecules of the beta 2 family of integrins play an important role in adhesion and migration of leukocytes to inflammatory sites. Several in vivo studies indicate that not only monoclonal antibodies (mAbs) directed against the common beta subunit (CD18) but also to the individual alpha subunits (CD11a, CD11b) can effectively inhibit different types of inflammation. In this study we report that in the adjuvant arthritis (AA) alpha CD11a, alpha CD11b, or even alpha CD18 treatment could not prevent disease development. Moreover, we examined the same mAbs in an acute nonspecific inflammation at different sites in the rat. We found that pretreatment with alpha CD11a or alpha CD11b could significantly block a zymosan peritonitis, but appeared to have no effect on a locally induced joint or dermal inflammation. Interestingly, alpha CD18 treatment, which blocks the entire CD11/CD18 complex, was able to inhibit the influx of inflammatory cells in a peritonitis as well as in a joint and dermal inflammation. These data not only indicate that the type of joint inflammation determines which adhesion molecules play a role in transendothelial migration, but also that involvement of the beta 2 integrins is highly site specific.


Long-term remission of atypical HUS with anti-factor H antibodies after cyclophosphamide pulses.
Anti-complement factor H (CFH) autoantibody (Ab)-associated atypical hemolytic uremic syndrome (aHUS) has a poor prognosis, but no consensus exists on its treatment. We report the follow-up of four children with anti-CFH Ab (8,000 to >32,000 arbitrary units)-associated aHUS after plasma exchanges (PEs), prednisone, and cyclophosphamide pulse therapy with the evolution of anti-CFH Ab titers and kidney function. Patient 1 received PEs + prednisone + cyclophosphamide pulses after two relapses following PEs and then PEs + rituximab. The other three patients were treated with PEs + prednisone + cyclophosphamide pulses as a first-line therapy. In our four patients, the induction protocol combining PEs + prednisone + cyclophosphamide pulses led to a rapid and sustained remission up to 6 years, 4 years and 4 months without any maintenance therapy. Kidney function was normal and anti-CFH Ab titer decreased, but remained detectable during remission without any clinical or biological signs of relapse. We demonstrate the long-term efficiency and safety of cyclophosphamide pulses combined with PEs and prednisone in anti-CFH Ab-associated aHUS leading to a prolonged decrease in anti-CFH Ab titers and prevention of relapses without the need for maintenance therapy.


[Summation of GABA- and glutamate-mediated currents in rat cortical neurons].
Whole-cell patch clamp recordings from isolated neurons from rat prefrontal cortex have been made to study the interaction of responses induced by application of GABA and glutamate. Two different pipette solutions were used in this research: the first one was based on CsCl, while the second one was CsF-based. With CsCl-based pipette solution being used, co-application of GABA (200 microM) and glutamate (200 microM) resulted in producing a total current smaller than the sum of the two individual responses. But with CsF-based pipette solution being used, the response to co-application of GABA (200 microM) and glutamate (200 microM) was equal to the sum of the two individual responses. These results suggest that there is a cross-modulation between GABA- and glutamate-mediated responses.


Project Management for Quality Improvement in Radiology.
This article outlines a structured approach for applying project management principles to quality improvement in radiology. We highlight the framework we use for managing improvement projects in our department and review basic project management principles. Project management involves techniques for executing projects effectively and efficiently. We recognize the following phases for managing improvement projects: idea, project evaluation and selection, role assignment, planning, improvement, and sustaining improvement.


Mortality in Parkinson's disease and its association with dementia and depression.
To compare the mortality rate in Parkinson's disease (PD) with a control group without PD, and to assess the relationship between mortality and features of PD. Ninety PD patients and 50 controls, mortality ascertained at 11 years follow-up. The hazard ratio (HR) for mortality in PD patients compared with controls was 1.64 (95% CI: 1.21-2.23). Multivariate analysis showed age, dementia and depression were independent predictors of mortality but age at onset of PD and severity of neurological symptoms were not. The HR for age was 1.09 (95% CI: 1.05-1.13), for dementia 1.94 (95% CI: 1.26-2.99), and for depression 2.66 (95% CI: 1.59-4.44). Mortality in PD is increased compared with controls. Psychological variables are important predictors of mortality in PD.


Image analysis in quantitative PCR. An application for the measurement of c-erbB-2 oncogene amplification in DNA from human tumours.
We present an application of image analysis for the direct quantification of PCR products after gel electrophoresis and ethidium bromide staining of DNA. This procedure has been applied to the development of an assay based on competitive PCR for the measurement of the degree of amplification of c-erbB-2 oncogene in DNA from human tumours. In this method two DNA species (genomic and competitor) compete for PCR amplification. Since results are calculated from the final competitor/genomic ratio any variable affecting the rate of PCR amplification has no effect on the accuracy of the ratio measurement. Results are reported which show that even large variations in the experimental conditions (number of PCR cycles, sample volumes and extracted DNA quality) did not interfere with the precision of the measurement of the competitor/genomic ratio.


EPA is Cardioprotective in Male Rats Subjected to Sepsis, but ALA Is Not Beneficial.
It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.


Molecular identification of Epitrix potato flea beetles (Coleoptera: Chrysomelidae) in Europe and North America.
Epitrix species (Coleoptera: Chrysomelidae) feed mostly on plants from the family Solanaceae and some of them are major pests of potato crops. All Epitrix species are morphologically highly similar, which makes them difficult to identify and limits their study and management. Identification of species is mostly based on the observation of the genitalia and requires a high level of expertise. Here, we propose a tool to reliably identify all developmental stages of the most economically important Epitrix species feeding on potato in Europe and North America (Epitrix cucumeris, Epitrix similaris, Epitrix tuberis, Epitrix subcrinita and Epitrix hirtipennis). We first sequenced two DNA markers (mitochondrial cytochrome c oxidase I (COI) and nuclear internal transcribed spacer 2 (ITS2)) to test their effectiveness in differentiating among six Epitrix species (126 specimens). Morphospecies of Epitrix were well-differentiated by both DNA barcodes and no mitochondrial introgression was detected. Then, we developed an RFLP-based diagnostic method and showed that unambiguous species discrimination can be achieved by using the sole restriction enzyme TaqI on COI polymerase chain reaction products. The tool proposed here should improve our knowledge about Epitrix species biology, distribution and host range, three capacities that are particularly important in the detection and management of these pest species. Specifically, this tool should help prevent the introduction of E. tuberis and E. subcrinita in Europe and limit the spread of the recently introduced E. cucumeris and E. similaris, with minimal disruption to Solanaceae trade.


Differential in vitro development of inflorescences in long and short day Lemna spp.: involvement of ethylene and polyamines.
In vitro-development of Lemna inflorescences on minimal medium is known to differ in long day (LDP) and short day (SDP) plants (Z. Pfl, physiol. 77, 395). In LDP pistil growth predominates, while in SDP stamen growth predominates. This indicates that LDP and SDP inflorescences differ in endogenous hormones and depend for a balanced male-female development on different plant-supplied factors (Z. Pfl. physiol. 80, 283 and 298). Here inflorescences of the LDP L. gibba and the SDP L. aequinoctialis were tested for differences in ethylene-polyamine (PA) relations, as ethylene and PAs are inversely related (shared precursor, mutual inhibition of synthesis), and exogenous ethylene has been shown previously to restore male-female balance in SDP inflorescences (Z. Pfl. physiol. 80, 283). Promotion of pistil or stamen growth indicates a predominance of ethylene and PAs in LDP and SDP, respectively. Hence, in LDP, exogenous PAs and inhibitors of ethylene synthesis, and in SDP, an inhibitor of PA-synthesis, were applied to restore the male-female balance in vitro. In L. aequinoctialis (SDP), application of methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of spermidine (SD) synthesis, resulted in near normal development via stamen inhibition and/or pistil promotion. In L. gibba (LDP), ethylene inhibition was effective, especially by aminoethoxyvinylglycine (AVG), which reduced pistil growth. Effects of alpha-aminooxyacetic acid (AOA) were less clear. Putrescine (PUT) promoted stamen growth under certain circumstances, perhaps acting as a precursor for the more active SD. SD effects were concentration-dependent for pistil and stamen. Most importantly, increases in SD turned pistil promotion into inhibition and almost normalised floral development. Spermine (SM) enhanced stamen growth. Results are conclusive that PA-ethylene relationships are involved in inflorescence development in a contrasting manner in LDP and SDP. It is apparent that in whole plants the LDP supplies the inflorescences with factors inhibiting ethylene and/or stimulating PA-synthesis. In SDP the converse is true.


Effects of neuromuscular blocking agents on central respiratory chemosensitivity in newborn rats.
Neuromuscular blocking agents suppress central respiratory activity through their inhibitory effects on preinspiratory neurons and the synaptic drive from preinspiratory neurons to inspiratory neurons. Central CO2-chemosensitive areas, which partly consist of CO2-excited neurons, in the rostral ventrolateral medulla are thought to provide tonic drive to the central respiratory network and involve cholinergic mechanisms, which led us to hypothesize that neuromuscular blocking agents can inhibit CO2-excited neurons and attenuate respiratory CO2 responsiveness. To test this hypothesis, we used isolated brainstem-spinal cord preparations from newborn rats. The increase of C4 burst frequency induced by a hypercapnic superfusate, i.e. respiratory CO2 responsiveness, was suppressed by the application of neuromuscular blocking agents, either d-tubocurarine (10, 100 microM) or vecuronium (100 microM). These agents (40 microM) also induced hyperpolarization and decreases in firing frequency of CO2-excited neurons in the rostral ventrolateral medulla. Our results demonstrate that neuromuscular blocking agents inhibit CO2-excited tonic firing neurons and attenuate respiratory CO2 responsiveness.


Spontaneous subclavian vein thrombosis.
A young man presented with swelling of his right arm and engorgement of the superficial veins over the shoulder. Bilateral upper limb venography was performed and confirmed the presence of thrombus in the right subclavian vein. Deep venous thrombosis (DVT) of the upper extremity is an unusual thrombotic event with a reported incidence of 1-2% of all cases of venous occlusion. Review of the literature reveals a number of diverse aetiologies, and no agreement regarding the best terminology for the subgroups of this disorder.


Neutralising antibody escape of SARS-CoV-2 spike protein: Risk assessment for antibody-based Covid-19 therapeutics and vaccines.
The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in Spike could affect efficacy of those treatments. Hence, monitoring of mutations is necessary to forecast and readapt the inventory of therapeutics. Different phylogenetic nomenclatures have been used for the currently circulating SARS-CoV-2 clades. The Spike protein has different hotspots of mutation and deletion, the most dangerous for immune escape being the ones within the receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, and N501Y. Convergent evolution has led to different combinations of mutations among different clades. In this review we focus on the main variants of concern, that is, the so-called UK (B.1.1.7), South African (B.1.351) and Brazilian (P.1) strains.


Role of coronary artery calcium score for risk stratification in patients with non significant perfusion defects by myocardial perfusion single photon emission computed tomography.
Myocardial perfusion scintigraphy (MPS) is an important diagnostic tool in the management of patients with suspected coronary artery disease (CAD). However, the presence of mild-moderate perfusion defects can be challenging and may lead to unnecessary cardiac catheterization. The coronary artery calcium (CAC) score is a method with excellent negative predictive value in the evaluation of CAD, but its role in this setting of patients has not been fully defined. This study aims to assess the potential of CAC in the prediction of cardiac adverse events in patients with suspected CAD with mild-moderate perfusion by MPS. We conducted a cohort study in 292 patients presenting with mild-moderate perfusion defects by MPS undergoing a CAC measurement. The patients were followed for a mean of 34 months for occurrence of major cardiac adverse events (MACE). The majority of the patients (64.7%) were male, mean age of 57.9 ± 12.6 years. During the follow-up there were 37 MACE. In multivariate Cox proportional hazards model, hypertension and CAC were independent predictors of MACE. The patients who presented a CAC score of ≥ 400 had a high risk of MACE (HR 20.9; 95% CI 4.79-91.42; p < 0.001). Kaplan-Meier curve showed a significant difference (log-rank χ²; p< 0.001) using CAC scores in predicting MACE. CAC score carries a powerful prognostic value in predicting adverse events in patients with suspected CAD and MPS with mild-moderate perfusion defects and may be useful in risk stratification of these patients.