Polysaccharide-based self-assembling nanohydrogels: An overview on 25-years research on pullulan

The aim of this overview is to review the evolution of the studies carried out, during more than 25 years, on nanohydrogels obtained by self-assembling of pullulan (PUL) using several hydrophobization strategies. After the first publications, mainly devoted to the preparation and characterization of PUL nanogels, a remarkable number of studies demonstrated how wide can be the field of applications within the main topic of biopharmaceutics. Numerous hydrophilic and lipophilic drugs were entrapped in the nanogel networks, consequently PUL nanogels have been proposed as delivery systems for single drugs and for combination therapies which allowed improvements of pharmacological activities and patient compliance. Furthermore, the large amount of water content allowed loading also proteins which could maintain their native structure and properties. Stimuli-sensitive and stealth PUL nanogel formulations allowed improving the performances of antitumor drugs. These nanohydrogels have also been studied for imaging techniques and for vaccines to be administered by injection and by mucosal application. The studies on PUL nanogels are still in progress and the perspectives for future researches are also addressed

The use of IASI data to identify systematic errors in the ECMWF forecasts of temperature in the upper stratosphere

Since data from the Infrared Atmospheric Sounding Interferometer (IASI) became available in 2007, a number of papers have appeared in the literature which have reported relatively large discrepancies between IASI spectra and forward calculations in the centre of the CO<sub>2</sub> Q-branch at 667 cm<sup>−1</sup>. In this paper we show that these discrepancies are primarily due to errors in the temperature profiles used in the forward calculations. In particular, we have used forecasts of temperature profiles from the European Centre for Medium-Range Weather Forecasts (ECMWF) to demonstrate that, for the case study considered in this paper, these profiles are affected by systematic errors of the order of ≈10 K at the level of the stratopause. To derive the magnitude and the spatial location of the systematic errors in the temperature profile, we have carried out forward/inverse calculations for a number of clear-sky, daytime, IASI tropical soundings over the sea. The forward calculations have been performed using atmospheric state vectors which have been obtained either from the direct inversion of the IASI radiances or from space-time co-located profiles derived from radiosonde observations and from the ECMWF model. To rule out any effect due to the accuracy of the forward model, we have performed the forward calculations using two independent models. The sensitivity of the temperature biases to the variability of the CO<sub>2</sub> profile and to spectroscopy errors has also been studied

Characteristics of visual evoked potentials related to the electro-clinical expression of reflex seizures in photosensitive patients with idiopathic occipital lobe epilepsy

Seizures provoked by visual stimuli may be induced by abnormal responses to light (photosensitivity) and structured patterns (patternsensitivity). In this study, we analysed visual evoked potentials (VEPs) in three different samples: i) 38 photosensitive patients (21 males, 17 females; mean age 10.0 ± 2.9 years) with idiopathic occipital lobe epilepsy and reflex seizures (RS); ii) 13 non-photosensitive patients (6 males, 7 females; mean age 11.7 ± 5.3) with idiopathic occipital lobe epilepsy; 20 healthy controls (12 males, 8 females; mean age 10.0 ± 3.4). After written informed consent, all subjects underwent a standard procedure of visual stimulation with intermittent light and pattern stimulation, under digital video-EEG recording. The EEG signal was processed off-line by averaging analysis for each stimulus to obtain the corresponding VEP. Comparisons among groups showed no significant differences for P100 latency. Higher P100 amplitude as well as higher after-discharge (AD) were found in photosensitive patients with RS. Thirty-seven of these patients had one or more RS during the procedure of stimulation for a total of 66 episodes. Significant increases of P100 amplitude and higher values of AD amplitude were found in relation to the occurrence of photoparoxysmal response (PPR) and/or seizures during full-field pattern stimulation. The increase in amplitude of the AD was higher when PPR was associated with seizures. The high amplitude of early VEP components confirms the abnormal hyperexcitability in the cortex of photosensitive patients with occipital lobe epilepsy. Moreover, the AD amplitude appears to be related to electro-clinical expression, being greater when PPR evolves into clinically evident seizures

Design of hybrid gels based on gellan-cholesterol derivative and P90G liposomes for drug depot applications

Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes a new class of hybrid gels that stem from the interaction between liposomes based on P90G phospholipid and the cholesterol derivative of the polysaccharide gellan. The mechanical properties of these gels and the delivery profiles of the anti-inflammatory model drug diclofenac embedded in such systems confirmed the suitability of these hybrid gels as a good candidate for drug depot applications

Partially scanned interferogram methodology applied to IASI for the retrieval of CO, CO_2, CH_4 and N_2O

The technique of partially scanned interferograms is applied to the retrieval of trace gases from Infrared Atmospheric Sounding Interferometer (IASI) observations. For the specific case of CO, CO2, CH4 and N2O, we show that this methodology allows us to retrieve trace gases column abundances at an unprecedented accuracy at the level of the single IASI footprint. The technique consists in transforming the IASI spectra back to the interferogram domain where we identify small regions that are mostly sensitive to single gas species. The retrieval is then performed by directly applying Least Squares estimation to these small segments of interferometric radiances. One of the main advantages of the technique is that it allows the efficient use of the information contained in all the IASI channels that are available in the absorption bands of a specific gas species. The retrieval technique has been applied to IASI radiances measured over the Mediterranean sea during the month of July 2010, one of the hottest months on record. Results have been validated against ground-based measurements. We have also carried out a comparison with Atmospheric Infrared Radiometer Sounder data and IASI retrievals obtained with usual variational approaches in the spectral domain

Understanding Childhood Neuroimmune Diseases of the Central Nervous System

Immune-mediated diseases of the central nervous system (CNS) in childhood are a heterogeneous group of rare conditions sharing the inflammatory involvement of the CNS. This review highlights the growing knowledge of childhood neuroimmune diseases that primarily affect the CNS, outlining the clinical and diagnostic features, the pathobiological mechanisms and genetics, current treatment options, and emerging challenges. The clinical spectrum of these conditions is increasingly expanded, and the underlying mechanisms of dysregulation of the immune system could vary widely. Cell-mediated and antibody-mediated disorders, infection-triggered and paraneoplastic conditions, and genetically defined mechanisms can occur in previously healthy children and can contribute to different stages of the disease. The careful evaluation of the clinical presentation and temporal course of symptoms, the specific neuroimaging and immunological findings, and the exclusion of alternative causes are mandatory in clinical practice for the syndromic diagnosis. A common feature of these conditions is that immunotherapeutic agents could modulate the clinical course and outcomes of the disease. Furthermore, specific symptomatic treatments and comprehensive multidisciplinary care are needed in the overall management. We focus on recent advances on immune-mediated demyelinating CNS disorders, autoimmune encephalitis, interferonopathies, and possible neuroimmune disorders as Rasmussen encephalitis. Better knowledge of these conditions could allow prompt diagnosis and targeted immunotherapy, to decrease morbidity and mortality as well as to improve clinical outcomes, reducing the burden of the disease due to possible long-term neuropsychiatric sequelae. Persisting controversies remain in the rigorous characterization of each specific clinical entity because of the relative rarity in children; moreover, in a large proportion of suspected neuroimmune diseases, the immune "signature" remains unidentified; treatment guidelines are mostly based on retrospective cohort studies and expert opinions; then advances in specific molecular therapies are required. In the future, a better characterization of specific immunological biomarkers may provide a useful understanding of the underlying pathobiological mechanisms of these conditions in order to individualize more tailored therapeutic options and paradigms. Multicenter collaborative research on homogeneous groups of patients who may undergo immunological studies and therapeutic trials could improve the characterization of the underlying mechanisms, the specific phenotypes, and tailored management

A survey among members of the Association of German Allergists (AeDA)

Background: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic presented unprecedented challenges to both inpatient and outpatient care. In order to maintain good care under necessary contact restrictions, especially in the outpatient sector, the use of telemedical applications was demanded and promoted. The exploratory survey among members of the Association of German Allergists (AeDA) was intended to show how these were received among allergists in private practice. Methods: The survey was restricted to actively practising members of the AeDA who had previously given their consent to receive such surveys (n = 437). They were invited by email to participate in a survey on the topic of "Telemedicine in everyday clinical practice in allergology". The survey included quantitative and qualitative questions on the use of telemedicine services before and during the pandemic and was conducted anonymously on the SoSci Survey platform. Participation was possible in the period from June to August 2020. Results: In all, 76 specialists with additional qualification in allergology took part in the survey. Of these, 71 completed the full questionnaire. Before the start of the pandemic-related contact restrictions, 46.5% (33/71) stated that they had used telemedicine in their clinical practice. This number increased to 73.2% (52/71) after 31 January 2020. The largest increase (4.3% vs. 15.6%) was seen in the area of video consultations. Furthermore, 43/76 participants can imagine integrating telemedicine services into their daily clinical routine in the future. Conclusion: The use of telemedical services, especially video consultations, increased significantly during the SARS-CoV‑2 pandemic in Germany. The majority of respondents perceive the implementation as positive and can imagine continuing to use telemedical methods after the end of the pandemic

The first, holistic immunological model of COVID‐19: Implications for prevention, diagnosis, and public health measures

The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi-organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10-15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose-binding lectin). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high-affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low-moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID-19 facilitates re-inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies ("viral auto-inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This "quantitative and time-/sequence-dependent" model has several implications for prevention, diagnosis, and therapy of COVID-19 at all ages

Fatal anaphylaxis to wheat after gluten-free diet in an adolescent with celiac disease

n/

Transition into adulthood: Tuberous sclerosis complex, S turge‐ W eber syndrome, and R asmussen encephalitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108590/1/epi12722.pd