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Avascular necrosis (AVN) is a severe complication of sickle cell disease (SCD) and involves principally the femoral head. Few data exist about the prevalence of lesions in other segments.In this cross-sectional study, 42 children (20 males and 22 females) underwent a magnetic resonance imaging (MRI) of the spine, upper arms, and femurs. The primary outcome was to define the prevalence and locations of bone infarcts.Forty-two patients completed the study; the total median age was 11.9 years (interquartile range = 9.5-13.9). Eleven patients (26.2%) were positive for altered bone findings for a total of 32 lesions. Most of the lesions were in the humerus 17 (53.1%), 11 (34.4%) in the femurs, and 4 (12.5%) in the vertebrae. The median number of vaso-occlusive crises (VOCs) was two and four for patients without and with bone lesions, respectively (p = .01). The annual rate of VOC is the best marker for the positive MRI (odds ratio = 82.6; p = .03), and it is correlated with the number of sites involved (p = .02).Our study highlights that the prevalence of skeletal lesions could be underestimated, and it provides the basis for clinical reasoning and tailored therapy in SCD children.

BACKGROUND Tomato is widely consumed throughout the world for its flavor and nutritional value. This functional food largely depends on the implementation of new strategies to maintain the nutraceutical value, e.g. lycopene concentration, and overcome the challenges of sustainable production and food security. The use of arbuscular mycorrhizal fungi (AMF)-based biostimulants represents one of the most promising tools for sustainable management of agricultural soils, being fundamental for organic food production, reducing fertilizers and pesticides use, and decreasing environmental damage. This study aimed at elucidating whether native arbuscular mycorrhizal fungi (AMF) could positively affect tomato yield and lycopene concentration. RESULTS Native AMF inoculum consisted of two inoculum types: the single species Claroideoglomus claroideum, and a mix of Scutellospora calospora, Acaulospora laevis, Claroideoglomus claroideum, and Claroideoglomus etunicatum. At the end of the study up to 78% of the root system was colonized by single inoculum. Tomato diameters in single and mix mycorrhizal plants showed increases of 80% and 35% respectively. Fresh weights were 84% and 38% higher with single and mix inocula compared with the controls, respectively. The lycopene concentration in tomato fruits of plants with single and mix inoculum was higher than controls. The lycopene concentration was 124.5% and 113.9% greater in single and mix than non-inoculated plants. CONCLUSION Tomato diameters, fresh weight and lycopene concentration was significantly higher in plants colonized by AMF compared with uninoculated plants. Results suggest that the role of single species Claroideoglomus claroideum could generate better plant performance due to its high production of extraradical mycelium. © 2021 Society of Chemical Industry.

The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein‐based versus regular cow's milk‐based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first‐degree relative affected by type 1 diabetes and with HLA‐conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 days with a median duration of study formula use of 63 days. During the intervention, 80% of the infants received study formula. Of these, 57% received study formula for at least 2 months. On average, 45.5 l of study formula were used per infant. Only 13% of the population had received a nonrecommended food by the age of 6 months. The dietary compliance was similar in the intervention and control arm. The reported cow's milk consumption by the families matched very well with measured serum casein IgA and IgG antibody concentration. To conclude, good compliance was observed in this randomized infant feeding trial. Compliance varied between the regions and those infants who were breastfed for a longer period of time had a shorter exposure to the study formula. High dietary compliance in infant feeding trial is necessary to allow accurate interpretation of study results., The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein‐based versus regular cow's milk‐based infant formula reduces the risk of type 1 diabetes. We describe good dietary compliance in the trial in terms of study formula feeding, feeding of non‐recommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first degree relative affected by type 1 diabetes and with HLA‐conferred susceptibility to type 1 diabetes.

Glioblastoma (GBM) is one of the most malignant and devastating brain tumors. The presence of highly therapy-resistant GBM cell subpopulations within the tumor mass, rapid invasion into brain tissues and reciprocal interactions with stromal cells in the tumor microenvironment contributes to an inevitable fatal prognosis for the patients. We highlight the most recent evidence of GBM cell crosstalk with mesenchymal stem cells (MSCs), which occurs either by direct cell-cell interactions via gap junctions and microtubules or cell fusion. MSCs and GBM paracrine interactions are commonly observed and involve cytokine signaling, regulating MSC tropism toward GBM, their intra-tumoral distribution, and immune system responses. MSC-promoted effects depending on their cytokine and receptor expression patterns are considered critical for GBM progression. MSC origin, tumor heterogeneity and plasticity may also determine the outcome of such interactions. Kinins and kinin-B1 and -B2 receptors play important roles in information flow between MSCs and GBM cells. Kinin-B1 receptor activity favors tumor migration and fusion of MSCs and GBM cells. Flow and image (tissue) cytometry are powerful tools to investigate GBM cell and MSC crosstalk and are applied to analyze and characterize several other cancer types.

Funding for international humanitarian aid falls far behind demand for disaster response, hampering the operations of international humanitarian organizations (IHOs). One remedy to close this gap is to increase the effectiveness of fundraising activities for IHOs. This remedy means spending as little as possible in fundraising activities but, at the same time, still receiving sufficient donations to implement disaster response programs in response to the needs that arise when disasters occur. We contribute to the literature by theoretically developing and estimating a conceptual framework that links donation behavior to the operations that IHOs aim to pursue; the framework incorporates operational costs communicated in appeals, fundraising efforts, and media attention. We argue that effects are not homogenous across disasters but that IHOs can leverage public attention and disaster and appeal characteristics, such as operational costs, to increase donations. We test the framework on a unique data set for disaster response programs operated by the International Federation of Red Cross and Red Crescent Societies (IFRC), covering 174 disasters to which the IFRC responded between 2010 and 2017.

To describe the outcome of Dravet syndrome (DS) in adolescents and adults we conducted a longitudinal retrospective study of two independent cohorts of 34 adolescents (group 1) and 50 adults (group 2). In both cohorts, we collected information about genetic mutation, and semiology of seizures at onset and during disease course. At the last evaluation, we considered the following features: epilepsy (distinguishing myoclonic/complete and nonmyoclonic/incomplete phenotype), neurologic signs, intellectual disability (ID), and behavioral disorders. Moreover, in both cohorts, we performed a correlation analysis between early characteristics of the disease and the outcome of DS with regard to seizure persistence, ID, behavioral disorder, and neurologic impairment at last evaluation. Group 1 includes 22 adolescents with complete form of DS and 12 with incomplete form; group 2 includes 35 adults with complete form and 15 with incomplete form. The seizures persisted in 73.6% of adolescents and in 80% of adults, but epilepsy severity progressively decreased through age. Seizure persistence correlated with the complete phenotype and with the occurrence of reflex seizures. At last evaluation, ID was moderate or severe in 70.5% of adolescents and in 80% of adults. The most severe cognitive and motor impairment was observed in patients with persisting seizures. The severity of cognition, language, and neurologic impairment at last evaluation correlated statistically with the complete phenotype. The study confirms that the global outcome of DS is poor in most cases, albeit epilepsy severity decreases throughout adulthood. The improvement of epilepsy throughout ages is not associated with improvement in intellectual abilities and motor skills; this confirms that the unfavorable outcome is not a pure consequence of epilepsy.

The aim of this paper is to provide a methodological approach to evaluate the nutritional sustainability of typical agro-food products, representing Mediterranean eating habits and included in the Mediterranean food pyramid.; Results: For each group of foods, suitable and easily measurable indicators were identified. Two macro-indicators were used to assess the nutritional sustainability of each product. The first macro-indicator, called 'business distinctiveness', takes into account the application of different regulations and standards regarding quality, safety and traceability as well as the origin of raw materials. The second macro-indicator, called 'nutritional quality', assesses product nutritional quality taking into account the contents of key compounds including micronutrients and bioactive phytochemicals. For each indicator a 0-10 scoring system was set up, with scores from 0 (unsustainable) to 10 (very sustainable), with 5 as a sustainability benchmark value. The benchmark value is the value from which a product can be considered sustainable. A simple formula was developed to produce a sustainability index.; Conclusion: The proposed sustainability index could be considered a useful tool to describe both the qualitative and quantitative value of micronutrients and bioactive phytochemical present in foodstuffs. This methodological approach can also be applied beyond the Mediterranean, to food products in other world regions. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

A series of functionalized α-chiral phosphonates was obtained by enzymatic reduction of the corresponding β-activated vinylphosphonate derivatives employing several ene-reductases of the Old Yellow Enzyme family as biocatalysts. The insufficient activation of the phosphonate group alone was compensated by introduction of an electron-withdrawing group at the β-position, which resulted in high levels of conversion (up to >99%). All active enzymes consistently furnished (R)-configurated products with exquisite stereoselectivity, thereby providing a stereo-complementary approach to current asymmetric hydrogenation protocols on similar compounds. Preparative-scale syntheses performed in aqueous buffer using formate/formate dehydrogenase for recycling of the nicotinamide cofactor granted access to β-keto-, cyano- and ester phosphonates from the (E)-isomers of α,β-unsaturated phosphonates in up to 72% isolated yield and >99% ee.

We report the use of bifunctional starting materials (ketoacids) in a diastereoselective Passerini three-center-two-component reaction. Study of the reaction scope revealed the required structural features for stereoselectivity in the isocyanide addition. In this system, an interesting isomerization of the primary Passerini product - the α-carboxamido lactone - into an atypical product, an α-hydroxy imide, was found to occur under acidic conditions. Furthermore, enantioenriched Passerini products can be generated from an enantioenriched ketoacid obtained by chemoenzymatic synthesis.

Summary Phytopathogens have developed elaborate mechanisms to attenuate the defense response of their host plants, including convergent evolution of complex pathways for production of the GA phytohormones, which were actually first isolated from the rice fungal pathogen Gibberella fujikuroi. The rice bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc) has been demonstrated to contain a biosynthetic operon with cyclases capable of producing the universal GA precursor ent-kaurene. Genetic (knock-out) studies indicate that the derived diterpenoid serves as a virulence factor for this rice leaf streak pathogen, serving to reduce the jasmonic acid-mediated defense response. Here the functions of the remaining genes in the Xoc operon are elucidated and the distribution of the operon in X. oryzae is investigated in over 100 isolates. The Xoc operon leads to production of the bioactive GA4, an additional step beyond production of the penultimate precursor GA9 mediated by the homologous operons recently characterized from rhizobia. Moreover, this GA biosynthetic operon was found to be widespread in Xoc (> 90%), but absent in the other major X. oryzae pathovar. These results indicate selective pressure for production of GA4 in the distinct lifestyle of Xoc, and the importance of GA to both fungal and bacterial pathogens of rice.

Preclinical Research A novel and promising approach to overcome the limits of single-target therapy is represented by the multitarget approach. This strategy aims to simultaneously modulate several targets involved in the pathophysiology of a multifactorial disease, with the potential to enhance therapeutic effectiveness and improve drug safety. Although there has been a marked growth in the design of multitarget drugs (MTDs) in the last years in the context of anti-Alzheimer and anti-cancer drug discovery, a parallel expansion was not observed in antipsychotic drugs, even that for psychiatric disorders there is a cogent medical need for new treatments. The discovery of new MTDs is a challenging task and we will describe the main strategies that have been developed over the years for the design of multifunctional molecules in antipsychotic drug discovery. In particular, we will focus on the few available MTDs based on the design of selective serotonin re-uptake inhibitors, used as antidepressants and in the treatment of schizophrenia. Drug Dev Res 77 : 437-443, 2016. © 2016 Wiley Periodicals, Inc.

Acute myeloid leukemia (AML) with deranged core-binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50–70% of patients cured using contemporary treatments. We analyzed the prognostic significance of clinical features on 58 patients with CBFβ-AML aged ≤60 years. Increasing age was the only predictor for survival (P

Background According to knowledge, patients with resectable pancreatic adenocarcinoma (PA) should receive adjuvant gemcitabine-based chemotherapy. Thus, the tumour node metastasis (TNM) classification is not used to determine post-operative treatment but rather only to establish patient prognosis. However, the TNM classification does not include strong factors influencing survival, such as perineural invasion or margin status. This study compared the survival of patients with very similar tumours. Methods From 1997 to 2007, 118 patients underwent pancreatectomy for PA. Twenty-six patients (22%) had long-term survival (>5 years; LTS group). According to the major prognostic factors of PA, we matched (1:1) patients in the LTS group with patients who did not have long-term survival (

Atmospheric non-equilibrium plasma is drawing interest as a promising tool for cancer treatment due to its blend of physical and chemical components that can exert anti-tumor effects. In this work, we investigate the effects of plasma treatment, performed by means of a wand electrode DBD driven by nanosecond high voltage pulses, on the viability, proliferation, and cell-cycle distribution of cells of mouse lymphoma. Results for direct treatment, with cell exposed to plasma while suspended in culture medium, and indirect treatment, where cells were added to culture medium previously activated by plasma treatment, are compared. A qualitative characterization by means of high-speed and iCCD imaging of the plasma discharges produced for the different operating conditions adopted in biological experiments, as well as a semi-quantitative study of the reactive species produced by plasma treatment in the culture medium, are also presented.

The traditional portrait of civil servants in Italy, as well as in most other countries, has always been one of not particularly efficient employees yet have the benefit of a secure job and can look forward to a comfortable retirement package. In order to change this image, public management reforms have largely focused on civil servants since the 1990s. However, many academics and practitioners claim some inertia in the reform implementation. In this article we aim to identify the determinants of such inertia in Italy's civil service reforms and we analyze data from 885 Italian municipalities expected to adopt the pay system reform for senior officials, as required by national legislature. Our findings stress the importance of accrued legitimacy, external public endorsement, and the influence of key internal stakeholders (like administrative leaders) as major vehicles to promote or slow down the implementation of administrative reforms in the public sector.

Cancer cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl mice model, the pathways involved in muscle, liver, and white adipose tissue wasting. These mice, which develop systematically pancreatic cancer, successfully reproduced many human symptoms afflicted with this disease, and particularly cachexia. Using the profiling analysis of pancreatic cancer-dependent cachectic tissues we found that Jak2/Stat3 pathways, p53 and NFkB results activated. Thus, our interest was focused on the Jak2 pathways because it is pharmacologically targetable with low toxicity and FDA approved drugs are available. Therefore, Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl mice were treated with the Jak2 inhibitor AG490 compound daily starting at 7 weeks old and for a period of 3 weeks and animals were sacrificed at 10 weeks old. Body weight for control mice was 27.84 ± 2.14 g, for untreated Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl was 14.97 ± 1.99 g, whereas in animals treated with the AG490 compound the weight loss was significantly less to 24.53 ± 2.04 g. Treatment with AG490 compound was efficient since phosphorylation of Jak2 and circulating interleukin-6 (IL6) levels were significantly reduced in cachectic tissues and in mice respectively. In conclusion, we found that Jak2/Stat3-dependent intracellular pathway plays an essential role since its pharmacological inhibition strongly attenuates cachexia progression in a lethal transgenic pancreatic cancer model. J. Cell. Physiol. 229: 1437–1443, 2014. © 2014 Wiley Periodicals, Inc.

This literature review aimed to critically analyze oncological results of vascular resection during pancreatectomy for adenocarcinoma in the light of the concept evolution of locally advanced tumors and microscopic complete resection. The literature search was conducted in PubMed and Medline for the period June 1994 to December 2012, retaining English as the language of publication. The review of 12 publications indicated that mortality and morbidity rates were not significantly different for pancreatectomy with or without venous resection (VR). Six comparative studies showed worse long-term survival in the VR group, though one meta-analysis, albeit with a significant population heterogeneity, demonstrated that the overall survival between VR and the control group was similar (12% vs. 17%). The compilation of 13 comparative studies showed a significantly lower rate of complete microscopic resection in the VR patient group compared to controls (63% vs. 77%; P = 0.001). Concerning pancreatectomy combined to arterial resection, the literature review indicated a significantly greater mortality and morbidity rate and a lower survival rate compared to pancreatic resection alone. Conflicting results concerning the long-term outcome of VR was due to the heterogeneity of the patient population. Since the only chance to cure patients of pancreatic adenocarcinoma is to obtain free resection margins, VR is a valid therapeutic option. But combined arterial resection to pancreatic resection does not appear to be recommended.

The analysis of high molecular weight (HMW) proteins from complex mixtures is still a challenge in proteomics. This work introduces a novel hydrogel obtained by the copolymerization of an allyl-PVA derivative with acrylamide and bisacrylamide and applies this matrix to the electrophoretic separation of HMW proteins. By inducing gelation of polyacrylamide in the presence of variable amounts of allyl-PVA, it is possible to control and vary the average gel porosity. This gel is easy to produce and handle and offers the advantage of being highly mechanically resistant and macroporous. The new matrix was tested in mono-dimensional separations of complex protein mixtures extracted from red cell membranes with different detergents. The improved performance of this macroporous matrix allowed to identify new proteins by MS and immunoblot analysis using specific antibodies. In particular, the resolution of proteins ranging in size between 97 and 279 kDa was greatly improved here compared to standard polyacrylamide gels, suggesting that this matrix can be a useful tool in routine analysis of HMW proteins in cell biology.