Synthesis and evaluation of poly(propylene fumarate)-grafted graphene oxide as nanofiller for porous scaffolds.

In an effort to obtain porous scaffolds with improved mechanical properties and biocompatibility, the current study discusses nanocomposite materials based on poly(propylene fumarate)/N-vinyl pyrrolidone(PPF/NVP) networks reinforced with polymer-modified graphene oxide (GO@PPF). The GO@PPF nanofiller was synthesized through a facile and convenient surface esterification reaction, and the successful functionalization was demonstrated by complementary techniques such as FT-IR, XPS, TGA and TEM. The PPF/NVP/GO@PPF porous scaffolds obtained using NaCl as a porogen were further characterized in terms of morphology, mechanical properties, sol fraction, and in vitro degradability. SEM and nanoCT examinations of NaCl-leached samples revealed networks of interconnected pores, fairly uniform in size and shape. We show that the incorporation of GO@PPF in the polymer matrix leads to a significant enhancement in the mechanical properties, which we attribute to the formation of denser and more homogenous networks, as suggested by a decreased sol fraction for the scaffolds containing a higher amount of GO@PPF. Moreover, the surface of mineralized PPF/NVP/GO@PPG scaffolds is uniformly covered in hydroxyapatite-like crystals having a morphology and Ca/P ratio similar to bone tissue. Furthermore, the preliminary biocompatibility assessment revealed a good interaction between PPF/PVP/GO@PPF scaffolds and murine pre-osteoblasts in terms of cell viability and proliferation.

Critical Design Factors for Electrochemical Aptasensors Based on Target-Induced Conformational Changes: The Case of Small-Molecule Targets.

Nucleic-acid aptamers consisting in single-stranded DNA oligonucleotides emerged as very promising biorecognition elements for electrochemical biosensors applied in various fields such as medicine, environmental, and food safety. Despite their outstanding features, such as high-binding affinity for a broad range of targets, high stability, low cost and ease of modification, numerous challenges had to be overcome from the aptamer selection process on the design of functioning biosensing devices. Moreover, in the case of small molecules such as metabolites, toxins, drugs, etc., obtaining efficient binding aptamer sequences proved a challenging task given their small molecular surface and limited interactions between their functional groups and aptamer sequences. Thus, establishing consistent evaluation standards for aptamer affinity is crucial for the success of these aptamers in biosensing applications. In this context, this article will give an overview on the thermodynamic and structural aspects of the aptamer-target interaction, its specificity and selectivity, and will also highlight the current methods employed for determining the aptamer-binding affinity and the structural characterization of the aptamer-target complex. The critical aspects regarding the generation of aptamer-modified electrodes suitable for electrochemical sensing, such as appropriate bioreceptor immobilization strategy and experimental conditions which facilitate a convenient anchoring and stability of the aptamer, are also discussed. The review also summarizes some effective small molecule aptasensing platforms from the recent literature.

Robust but weak winter atmospheric circulation response to future Arctic sea ice loss.

The possibility that Arctic sea ice loss weakens mid-latitude westerlies, promoting more severe cold winters, has sparked more than a decade of scientific debate, with apparent support from observations but inconclusive modelling evidence. Here we show that sixteen models contributing to the Polar Amplification Model Intercomparison Project simulate a weakening of mid-latitude westerlies in response to projected Arctic sea ice loss. We develop an emergent constraint based on eddy feedback, which is 1.2 to 3 times too weak in the models, suggesting that the real-world weakening lies towards the higher end of the model simulations. Still, the modelled response to Arctic sea ice loss is weak: the North Atlantic Oscillation response is similar in magnitude and offsets the projected response to increased greenhouse gases, but would only account for around 10% of variations in individual years. We further find that relationships between Arctic sea ice and atmospheric circulation have weakened recently in observations and are no longer inconsistent with those in models.

A carbon footprint study of the Canadian medical residency interview tour.

BACKGROUND: Each spring, thousands of Canadian medical students travel across the country to interview for residency positions, a process known as the CaRMS tour. Despite the large scale of travel, the CaRMS tour has received little environmental scrutiny. PURPOSE: To estimate the national carbon footprint of flights associated with the CaRMS tour, as well as reductions in emissions achievable by transitioning to alternative models. METHODS: We developed a three-question online commuter survey to collect the unique travel itineraries of applicants in the 2020 CaRMS tour. We calculated the emissions associated with all flights and modelled expected emissions for two alternative in-person interview models, and two virtual interview models. RESULTS: We collected 960 responses out of 2943 applicants across all 17 Canadian medical schools. We calculated the carbon footprint of flights for the 2020 CaRMS as 4239 tCO2e (tonnes of carbon dioxide equivalents), averaging 1.44 tCO2e per applicant. The average applicant's tour emissions represent 35.1% of the average Canadian's annual household carbon footprint, and the emissions of 26.7% of respondents exceeded their entire annual '2050 carbon budget.' Centralized in-person interviews could reduce emissions by 13.7% to 74.7%, and virtual interviews by at least 98.4% to 99.9%. CONCLUSIONS: Mandatory in-person residency interviews in Canada contribute significant emissions and reflect a culture of emissions-intensive practices. Considerable decarbonization of the CaRMS tour is possible, and transitioning to virtual interviews could eliminate the footprint almost entirely.

A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging.

PURPOSE: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). METHODS: We retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used. RESULTS: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients. CONCLUSIONS: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.

Impact of Covid-19 on farming systems in Europe through the lens of resilience thinking.

Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.

Improving the Voltammetric Determination of Hg(II): A Comparison Between Ligand-Modified Glassy Carbon and Electrochemically Reduced Graphene Oxide Electrodes.

A new thiosemicarbazone ligand was immobilized through a Cu(I)-catalyzed click reaction on the surface of glassy carbon (GC) and electrochemically reduced graphene oxide (GC-ERGO) electrodes grafted with phenylethynyl groups. Using the accumulation at open circuit followed by anodic stripping voltammetry, the modified electrodes showed a significant selectivity and sensibility for Hg(II) ions. A detection limit of 7 nM was achieved with the GC modified electrodes. Remarkably, GC-ERGO modified electrodes showed a significantly improved detection limit (0.8 nM), sensitivity, and linear range, which we attribute to an increased number of surface binding sites and better electron transfer properties. Both GC and GC-ERGO modified electrodes proved their applicability for the analysis of real water samples.

How often we diagnose allergy to ranitidine?

H2 receptors' antagonists (H2RA) are widely used drugs and they are generally well-tolerated. Ranitidine hypersensitivity reactions (HR) are rarely reported. The article emphasizes the importance of recognizing ranitidine as a cause of anaphylaxis and the advantages and limits of allergological evaluation to establish a positive diagnose. We reviewed a series of published cases of ranitidine-induced hypersensitivity reactions, starting from a clinical case presentation. Moreover, we analyzed the ranitidine related adverse events in the Eudravigilance European database of adverse reactions. Most of the allergic reactions induced by ranitidine are type I HR with immediate onset after exposure, with variable clinical presentation. But in a few cases, there were also described delayed reactions, some after occupational exposure. The article underlines the importance of allergy evaluation to avoid future contact with the drug to reduce the risk of more severe reactions. The suspected reactions should be reported, allowing pharmacovigilance systems to analyse them and to establish further recommendations for clinicians.

Celiac disease: a multi-faceted medical condition.

Celiac disease (CD) is a systemic condition of autoimmune origin, affecting genetically predisposed individuals who at some point lose tolerance towards dietary gluten. Prevalence in the general population is 0.5 - 1%, with a higher frequency in women. The most important environmental factor for CD is ingestion of specific gluten peptides. It triggers a sequence of molecular events, involving the intestinal permeability and the immune system, which ends in damage of the intestinal mucosa. A number of studies have demonstrated the correlation between the intestinal microbiota and celiac disease. MicroRNAs through their regulatory role on gene expression have been implicated in the pathogenesis of CD and suggested as potential biomarkers. In the pediatric and adult population, CD displays different clusters of clinical symptoms. Persistent diarrhea, abdominal pain and involuntary weight loss are the classic symptoms of CD. In the majority of cases diagnosis relies on the combination of serum autoantibodies (anti-transglutaminase and anti-endomisium IgA) and duodenal biopsy showing villous atrophy, crypt hyperplasia and intraepithelial lymphocytes. Observance of a lifelong gluten-free diet, which interrupts the immune response to gluten peptides, is the only effective treatment of CD.

Hema-Functionalized Graphene Oxide: a Versatile Nanofiller for Poly(Propylene Fumarate)-Based Hybrid Materials.

Poly(propylene fumarate) (PPF) is a linear unsaturated polyester which has been widely investigated for tissue engineering due to its good biocompatibility and biodegradability. In order to extend the range of possible applications and enhance its mechanical properties, current approaches consist in the incorporation of various fillers or obtaining blends with other polymers. In the current study we designed a reinforcing agent based on carboxylated graphene oxide (GO-COOH) grafted with 2-hydroxyethyl methacrylate (GO@HEMA) for poly(propylene fumarate)/poly(ethylene glycol) dimethacrylate (PPF/PEGDMA), in order to enhance the nanofiller adhesion and compatibility with the polymer matrix, and in the same time to increase the crosslinking density. The covalent modification of GO-COOH was proved by Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and Raman spectroscopy. The mechanical properties, water uptake capacity, morphology, biodegradability, mineralization and in vitro cytotoxicity of PPF/PEGDMA hybrid materials containing GO@HEMA were investigated. A 14-fold increase of the compressive modulus and a 2-fold improvement in compressive strength were observed after introduction of the nanofiller. Moreover, the decrease in sol fraction and solvent swelling in case of the hybrid materials containing GO@HEMA suggests an increase of the crosslinking density. SEM images illustrate an exfoliated structure at lower nanofiller content and a tendency for agglomeration at higher concentrations. Finally, the synthesized hybrid materials proved non-cytotoxic to murine pre-osteoblast cells and induced the formation of hydroxyapatite crystals under mineralization conditions.

Rutile RuxTi1-xO2 nanobelts to enhance visible light photocatalytic activity.

We herein report on the synthesis by a facile sol-gel method without templates for preparing rutile RuxTi1-xO2 (x = 0.16; 0.07; 0.01) nanobelts with exposed (001) facets. The rutile nanobelts with exposure (001) facets, favor the separation photogenerated electron-hole pairs and inhibit the recombination of the electron-hole pairs resulting in the increase of the number of main superoxide and hydroxyl radicals. The photocatalytic properties of the rutile RuxTi1-xO2 nanobelts were evaluated by discoloring of MB (methylene blue) dye under sunlight irradiation at an intensity of 40000 lx. It was also done a thorough interface analysis to determine the band energy.

Cellulose acetate/layered double hydroxide adsorptive membranes for efficient removal of pharmaceutical environmental contaminants.

The increasing amount of residual pharmaceutical contaminants in wastewater has a negative impact on both the environment and human health. In the present study, we developed new cellulose acetate/Mg-Al layered double hydroxide (Mg-Al LDH) nanocomposite membranes as an efficient method to remove pharmaceutical substances from wastewater. The morphology, porosity, surface properties and thermal stability of nanocomposite membranes containing various amounts of nanofiller were evaluated by scanning electron microscopy (SEM), X-ray microtomography (µCT), contact angle measurements and thermogravimetric analysis (TGA). The Mg-Al LDH nanofiller showed a high degree of exfoliation in the polymer matrix, evidenced by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The hydrodynamic properties and adsorption capacity were evaluated with pure water and aqueous solutions of two common drugs, diclofenac sodium (DS) and tetracycline (TC), and the nanocomposite membranes showed an improved permeability compared with neat cellulose acetate. The membrane prepared with 4 wt.% Mg-Al LDH loading exhibited the highest water flux compared with the pure polymer one (529 vs 36 L·m-2·h-1) and a tenfold increase in adsorption capacity for DS. This enhancement is attributed to electrostatic interactions between the negatively charged drug molecule and positively charged Mg-Al LDH layers. Conversely, in the case of TC, the increase in adsorption capacity was smaller and was assigned to hydrogen bonding interactions between the drug molecule and the nanofiller.

CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells.

Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis. Mice lacking CD1d-expressing B cells develop exacerbated disease compared to wild-type mice, and fail to respond to treatment with the prototypical iNKT cell agonist α-galactosylceramide. The absence of lipid presentation by B cells alters iNKT cell activation with disruption of metabolism regulation and cytokine responses. Thus, we identify a mechanism by which Bregs restrain excessive inflammation via lipid presentation.

The Influence of Physical Exercise on Smoking Patients with Peripheral Arterial Disease.

Smoking should be identified as a major risk factor for Peripheral arterial disease. The purpose of this prospective, randomized, controlled clinical study was to determine whether a rehabilitation program is more efficient than the usual healthcare assistance (medication, hygiene and diet) for improving walking function on the smoking and nonsmoking patients with PAD. For smokers, there were no significant differences after 12 weeks and also 24 weeks, although the 4MWS mean values increased compared to the control. At 24 weeks study time point nonsmokers in the group performed special massage techniques along with the supervised kinesiotherapy had significantly greater improvement in their 4MWS, compared to the group with physical exercises or control. A well-structured rehabilitation program, in terms of intensity, duration and frequency may be of great help for improving the functional status of these patients with peripheral ischemia syndrome.

Linear and nonlinear parameters of heart rate variability in ischemic stroke patients.

INTRODUCTION: Cardiovascular system presents cortical modulation. Post-stroke outcome can be highly influenced by autonomic nervous system disruption. Heart rate variability (HRV) analysis is a simple non-invasive method to assess sympatho-vagal balance. OBJECTIVES: The purpose of this study was to investigate cardiac autonomic activity in ischemic stroke patients and to asses HRV nonlinear parameters beside linear ones. METHODS: We analyzed HRV parameters in 15 right and 15 left middle cerebral artery ischemic stroke patients, in rest condition and during challenge (standing and deep breathing). Data were compared with 15 age- and sex-matched healthy controls. RESULTS: There was an asymmetric response after autonomic stimulation tests depending on the cortical lateralization in ischemic stroke patients. In resting state, left hemisphere stroke patients presented enhanced parasympathetic control of the heart rate (higher values for RMSSD, pNN50 and HF in normalized units). Right hemisphere ischemic stroke patients displayed a reduced cardiac parasympathetic modulation during deep breathing test. Beside time and frequency domain, using short-term ECG monitoring, cardiac parasympathetic modulation can also be assessed by nonlinear parameter SD1, that presented strong positive correlation with time and frequency domain parameters RMSSD, pNN50, HFnu, while DFA α1 index presented negative correlation with the same indices and positive correlation with the LFnu and LF/HF ratio, indicating a positive association with the sympatho-vagal balance. CONCLUSIONS: Cardiac monitoring in clinical routine using HRV analysis in order to identify autonomic imbalance may highlight cardiac dysfunctions, thus helping preventing potential cardiovascular complications, especially in right hemisphere ischemic stroke patients with sympathetic hyperactivation.

Ultrastable Silicon Cavity in a Continuously Operating Closed-Cycle Cryostat at 4 K.

We report on a laser locked to a silicon cavity operating continuously at 4 K with 1×10^{-16} instability and a median linewidth of 17 mHz at 1542 nm. This is a tenfold improvement in short-term instability, and a 10^{4} improvement in linewidth, over previous sub-10-K systems. Operating at low temperatures reduces the thermal noise floor and, thus, is advantageous toward reaching an instability of 10^{-18}, a long-sought goal of the optical clock community. The performance of this system demonstrates the technical readiness for the development of the next generation of ultrastable lasers that operate with an ultranarrow linewidth and long-term stability without user intervention.

1.5 µm Lasers with Sub-10 mHz Linewidth.

We report on two ultrastable lasers each stabilized to independent silicon Fabry-Pérot cavities operated at 124 K. The fractional frequency instability of each laser is completely determined by the fundamental thermal Brownian noise of the mirror coatings with a flicker noise floor of 4×10^{-17} for integration times between 0.8 s and a few tens of seconds. We rigorously treat the notorious divergences encountered with the associated flicker frequency noise and derive methods to relate this noise to observable and practically relevant linewidths and coherence times. The individual laser linewidth obtained from the phase noise spectrum or the direct beat note between the two lasers can be as small as 5 mHz at 194 THz. From the measured phase evolution between the two laser fields we derive usable phase coherence times for different applications of 11 to 55 s.

NF-κB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer.

The transcription factor nuclear factor kappa B (NF-κB) and the long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) have diverse functional roles in cancer. In this study, we show that upregulation of HOTAIR induced platinum resistance in ovarian cancer, and increased HOTAIR levels were observed in recurrent platinum-resistant ovarian tumors vs primary ovarian tumors. To investigate the role of HOTAIR during DNA damage induced by platinum, we monitored double-strand breaks and show that HOTAIR expression results in sustained activation of DNA damage response (DDR) after platinum treatment. We demonstrate that ectopic expression of HOTAIR induces NF-κB activation during DDR and interleukin-6 and interleukin-6 expression, both key NF-κB target genes. We show that HOTAIR regulates activation of NF-κB by decreasing Iκ-Bα (NF-κB inhibitor) and establish that by inducing prolonged NF-κB activation and expression of NF-κB target genes during DNA damage, HOTAIR has a critical role in cellular senescence and platinum sensitivity. Our findings suggest that an NF-κB-HOTAIR axis drives a positive-feedback loop cascade during DDR and contributes to cellular senescence and chemotherapy resistance in ovarian and other cancers.

Kinetic Program and Functional Status in Patients with Parkinson's Disease.

The main purpose of kinetic program integrated in complex medical assistance of PD patients is the improvement of life quality, through amelioration of self-care activities, and possibility of making various activities in stability, balance and coordination conditions. We choose the kinetics techniques according to the clinical form and the gravity of the functional deficit. Taking into consideration the locomotors dysfunctional status, almost patients were included in the second and third evolutional stages. For quantize the results and monitories the patients with assessment of the kinetic program benefits we have use different scales and questionnaires. The age of the patients was over 45 years and more patients were male then women; this aspect confirm the increase frequency of disease in the male subjects. The individual and global clinical motor aspects were been influenced by the kinetic program. The global functional impact upon the individual general state was appreciated with scale FIM scale (Functional Independence Measure). Each patient and the entire studied group had presented an increase of the final motor score; this evolution mode proved the important of the kinetic program in the management of the Parkinsonism patient global state. "The PD patients have not be help" in the quotidian activities performance - is one of the kinetic rules that has be respected by all the family patient members.

Autonomic impairment in patients with migraine.

OBJECTIVE: Heart rate variability analysis of electrocardiogram is becoming an increasingly common method to non-invasively evaluate autonomic nervous function. The aim of the study was to investigate cardiac autonomic function in subjects with and without migraine by using 24-hour ambulatory electrocardiographic recordings. PATIENTS AND METHODS: We investigated 27 subjects with migraine (10 with migraine with aura and 17 without aura) during headache free periods and 10 age-matched healthy control subjects. The migraine was diagnosed using the International Classification of Headache Disorders 2nd Edition criteria. Beck Depression and Beck Anxiety Inventory forms were completed by all subjects. Time and frequency-domain of HRV was analyzed for two periods: diurnal and nocturnal. RESULTS: We found an increased frequency of anxiety and depressive symptoms in migraine patients, especially in migraine with aura group. The heart rate variability parameters SDNN, RMSSD, high frequency were decreased and low frequency was increased in migraine patients during night period compared with normal subjects, most affected were migraine with aura patients. During day period we found modification for SDNN, RMSSD and high frequency parameters only in migraine with aura group. CONCLUSIONS: Reduced parasympathetic activity with sympathetic predominance was found in migraine patients during the night period, most affected being migraine with aura patients.