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Chronic exposure to high circulating levels of glucocorticoids (GCs) may be a key risk factor for Alzheimer's Disease (AD) development and progression. In addition, hyper-activation of glucocorticoid receptors (GRs) induces brain alterations comparable to those produced by AD. In transgenic mouse models of AD, GCs increase the production of the most important and typical hallmarks of this dementia such as: Aβ40, Aβ42 and tau protein (both the total tau and its hyperphosphorylated isoforms). Moreover, GCs in brain are pivotal regulators of dendritic spine turnover and microglia activity, two phenomena strongly altered in AD. Although it is well-established that GCs primes the neuroinflammatory response in the brain to some stimuli, it is unknown whether or how GRs modulates dendritic spine plasticity and microglia activity in AD. In this study, we evaluated, using combined Golgi Cox and immunofluorescence techniques, the role of GR agonists and antagonists on dendritic spine plasticity and microglia activation in hippocampus of 3xTg-AD mice. We found that dexamethasone, an agonist of GRs, was able to significantly reduce dendritic spine density and induced proliferation and activation of microglia in CA1 region of hippocampus of 3xTg-AD mice at 6 and 10 months of age. On the contrary, the treatment with mifepristone, an antagonist of GRs, strongly enhanced dendritic spine density, decreased microglia density and improved the behavioural performance of 3xTg-AD mice. Additionally, primary microglial cells in vitro were directly activated by dexamethasone. Together, these data demonstrate that stress exacerbates AD and promotes a rapid progression of the pathology acting on both neurons and glial cells, supporting an important pro-inflammatory role of GC within CNS in AD. Consequently, these results further strengthen the need to test clinical interventions that correct GCs dysregulation as promising therapeutic strategy to delay the onset and slow down the progression of AD.

Histochemical techniques are widely applied in biomedical research and, during the last twenty years, they were among the methods used in more than 590,000 scientific articles in indexed journals. However, a very small percentage of these papers were published in strictly histochemical journals. A possible strategy to widen the audience of the histochemical journals making them attractive to non-histochemist authors might be to publish and make open-access available the proceedings of the meetings and conferences of valued scientific societies whose fellows use microscopy and histochemistry in their experimental activity. In the last years’ experience of the European Journal of Histochemistry, this approach was effective to increase the number of published articles on stem cells and development, connective tissue and nerve cell biology.

The main step in the assessment of nanomaterial safety and suitability for biomedical use is the location and the dynamic tracking of nanoparticles (NPs) inside cells or tissues. To precisely investigate the uptake mechanisms and intracellular fate of NPs, transmission electron microscopy is the technique of choice; however, the detection of NPs may sometimes be problematic. In fact, while NPs containing strongly electron dense (e.g., metal) components do not require specific detection methods at the ultrastructural level, organic NPs are hardly detectable in the intracellular environment due to their intrinsic moderate electron density. In this study, the critical-electrolyte-concentration Alcian Blue method set up by Schofield et al. in 1975 was applied to track hyaluronic-acid-based NPs in muscle cells in vitro. This long-established histochemical method proved to be a powerful tool allowing to identify not only whole NPs while entering cells and moving into the cytoplasm, but also their remnants following lysosomal degradation and extrusion.

Background: The purpose of this study was to compare the accuracy of a smartphone application and a mechanical pedometer for step counting at different walking speeds and mobile phone locations in a laboratory context. Methods: Seventeen adults wore an iPphone6© with Runtastic Pedometer© application (RUN), at 3 different locations (belt, arm, jacket) and a pedometer (YAM) at the waist. They were asked to walk on an instrumented treadmill (reference) at various speeds (2, 4 and 6 km/h). Results: RUN was more accurate than YAM at 2 km/h (p

The best way to disseminate culture is, nowadays, the creation of scenarios with virtual and augmented reality that supply the visitors of museums with a powerful, interactive tool that allows to learn sometimes difficult concepts in an easy, entertaining way. 3D models derived from reality-based techniques are nowadays used to preserve, document and restore historical artefacts. These digital contents are also powerful instrument to interactively communicate their significance to non-specialist, making easier to understand concepts sometimes complicated or not clear. Virtual and Augmented Reality are surely a valid tool to interact with 3D models and a fundamental help in making culture more accessible to the wide public. These technologies can help the museum curators to adapt the cultural proposal and the information about the artefacts based on the different type of visitor’s categories. These technologies allow visitors to travel through space and time and have a great educative function permitting to explain in an easy and attractive way information and concepts that could prove to be complicated. The aim of this paper is to create a virtual scenario and an augmented reality app to recreate specific spaces in the Capitoline Museum in Rome as they were during Winckelmann’s time, placing specific statues in their original position in the 18th century.

Higher mass-normalized net energy cost of walking (NetCw/kg) and mechanical pendular recovery are observed in obese compared to lean adults. This study aimed to investigate the effect of different classes of obesity on the energetics and mechanics of walking and to explore the relationships between body mass, NetCw/kg and gait mechanics by using principal component analysis (PCA). NetCw/kg and gait mechanics were computed in severely obese (SOG; n = 18, BMI = 40.1 ± 4.4 kg·m−2), moderately obese (MOG; n = 17, BMI = 32.2 ± 1.5 kg·m−2) and normal-weight (NWG; n = 13, BMI = 22.0 ± 1.5 kg·m−2) adults during five walking trials (0.56, 0.83, 1.11, 1.39, 1.67 m·s−1) on an instrumented treadmill. NetCw/kg was significantly higher in SOG compared to NWG (p = 0.019), with no significant difference between SOG and MOG (p = 0.14), nor between MOG and NWG (p = 0.27). Recovery was significantly higher in SOG than in NWG (p = 0.028), with no significant difference between SOG and MOG (p = 0.13), nor between MOG and NWG (p = 0.35). PCA models explained between 17.0% and 44.2% of the data variance. This study showed that: (1) obesity class influences the gait energetics and mechanics; (2) PCA was able to identify two components, showing that the obesity class is associated with lower walking efficiency and better pendulum-like characteristics.

Nanomedical research necessarily involves the study of the interactions between nanoparticulates and the biological environment. Transmission electron microscopy has proven to be a powerful tool in providing information about nanoparticle uptake, biodistribution and relationships with cell and tissue components, thanks to its high resolution. This article aims to overview the transmission electron microscopy techniques used to explore the impact of nanoconstructs on biological systems, highlighting the functional value of ultrastructural morphology, histochemistry and microanalysis as well as their fundamental contribution to the advancement of nanomedicine.

This study aimed to investigate the effects of supervised exercise training (SET) on spatiotemporal gait and foot kinematics parameters in patients with symptomatic lower extremity peripheral artery disease (PAD) during a 6 min walk test. Symptomatic patients with chronic PAD (Fontaine stage II) following a 3 month SET program were included. Prior to and following SET, a 6 min walk test was performed to assess the 6 min walking distance (6MWD) of each patient. During this test, spatiotemporal gait and foot kinematics parameters were assessed during pain-free and painful walking conditions. Twenty-nine patients with PAD (65.4 ± 9.9 years.) were included. The 6MWD was significantly increased following SET (+10%; p ≤ 0.001). The walking speed (+8%) and stride frequency (+5%) were significantly increased after SET (p ≤ 0.026). The stride length was only significantly increased during the pain-free walking condition (+4%, p = 0.001), whereas no significant differences were observed during the condition of painful walking. Similarly, following SET, the relative duration of the loading response increased (+12%), the relative duration of the foot-flat phase decreased (−3%), and the toe-off pitch angle significantly increased (+3%) during the pain-free walking condition alone (p ≤ 0.05). A significant positive correlation was found between changes in the stride length (r = 0.497, p = 0.007) and stride frequency (r = 0.786, p ≤ 0.001) during pain-free walking condition and changes in the 6MWD. A significant negative correlation was found between changes in the foot-flat phase during pain-free walking condition and changes in the 6MWD (r = −0.567, p = 0.002). SET was found to modify the gait pattern of patients with symptomatic PAD, and many of these changes were found to occur during pain-free walking. The improvement in individuals’ functional 6 min walk test was related to changes in their gait pattern.

Abstract Background Tumor-associated macrophages (TAMs) are abundant in gliomas and immunosuppressive TAMs are a barrier to emerging immunotherapies. It is unknown to what extent macrophages derived from peripheral blood adopt the phenotype of brain-resident microglia in pre-treatment gliomas. The relative proportions of blood-derived macrophages and microglia have been poorly quantified in clinical samples due to a paucity of markers that distinguish these cell types in malignant tissue. Results We perform single-cell RNA-sequencing of human gliomas and identify phenotypic differences in TAMs of distinct lineages. We isolate TAMs from patient biopsies and compare them with macrophages from non-malignant human tissue, glioma atlases, and murine glioma models. We present a novel signature that distinguishes TAMs by ontogeny in human gliomas. Blood-derived TAMs upregulate immunosuppressive cytokines and show an altered metabolism compared to microglial TAMs. They are also enriched in perivascular and necrotic regions. The gene signature of blood-derived TAMs, but not microglial TAMs, correlates with significantly inferior survival in low-grade glioma. Surprisingly, TAMs frequently co-express canonical pro-inflammatory (M1) and alternatively activated (M2) genes in individual cells. Conclusions We conclude that blood-derived TAMs significantly infiltrate pre-treatment gliomas, to a degree that varies by glioma subtype and tumor compartment. Blood-derived TAMs do not universally conform to the phenotype of microglia, but preferentially express immunosuppressive cytokines and show an altered metabolism. Our results argue against status quo therapeutic strategies that target TAMs indiscriminately and in favor of strategies that specifically target immunosuppressive blood-derived TAMs.

Abstract Background Cancer treatment during pregnancy is a growing problem especially now that women delay childbearing. Systemic treatment of these malignancies during pregnancy centers mainly on the anticancer drugs anthracyclines, widely used in treating hematological and breast cancer during pregnancy and sometimes associated with early and late toxicity for the fetus. Owing to concern about their cardiac and neurodevelopmental toxicity more information is needed on which anthracycline to prefer and whether they can safely guarantee a cardiotoxicity-free outcome in the fetus. Discussion The major research findings underline anthracycline-induced dose-dependent effects, including cardiotoxicity, many avoidable. Partly because the placenta acts mainly as a barrier, research findings indicate low transplacental anthracycline transfer. Anthracycline-induced teratogenicity depends closely on when patients receive chemotherapy. Anthracycline cardiac toxicity may depend on the association with drugs that inhibit or induce placental P-glycoprotein (P-gp). P-gp-induced drug interactions may alter placental P-gp barrier function and subsequently change fetal exposure. Though many anthracyclines have acceptable safety profiles clinical studies suggest giving idarubicin with special caution. Patients and doctors who care for pregnant women should whenever possible avoid prematurity and hence reduce prematurity-induced medical complications at birth and in the long-term. Information is lacking on long-term anthracycline-induced effects. Conclusion Pregnant women receiving anthracycline-based chemotherapy should undergo regular, state-of-the-art diagnostic imaging to detect fetal drug-induced cardiac damage early, and allow alternative therapeutic options. Recognizing drug-induced interactions and understanding the most vulnerable fetuses will help in choosing tailored therapy. Future research on placental transport, blood-brain barrier drug passage and pharmacokinetics will improve the way we manage these difficult-to-treat patients and their fetuses.

• There are no publications on the use of educational escape room (EER) in an accelerated nursing program • The (EER) is an interactive learning activity to evaluate learning outcomes • The activity is low-cost and feasible to implement in other accelerated nursing programs An educational escape room (EER) was developed as an innovative strategy for summative evaluation at the end of the first semester in a medical/surgical course within an accelerated nursing program. Learning outcomes were focused on recognizing abnormal vital signs of a decompensating patient, prioritizing nursing interventions, role-playing as a rapid response nurse, collaborating with peers to complete each puzzle, interpreting findings, and discovering medication errors. Debriefing allowed faculty to provide feedback on the achievement of the learning outcomes. Most students agreed that the EER allowed them to meet each learning outcome. This project supported the usefulness of EERs for the evaluation of student learning outcomes in a fast-paced program that may be similar to the speed at which associate degree programs prepare students. [ABSTRACT FROM AUTHOR]

Oxygen–ozone (O2–O3) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O3 concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O2–O3 gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O3 stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-β1 secretion, while in LPS-activated fibroblasts, O3 stimulated only antioxidant response and cytokines secretion. Therefore, the low O3 concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated.

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e., matrisome) and its aging-associated changes. In this study, skeletal muscle proteins were isolated from whole gastrocnemius muscles of adult (12 mo.) and old (24 mo.) mice using three sequential extractions, each one analyzed by liquid chromatography with tandem mass spectrometry. Muscle sections were investigated using fluorescence- and transmission electron microscopy. This study provided the first characterization of the matrisome in the old SM demonstrating several statistically significantly increased matrisome proteins in the old vs. adult SM. Several proteomic findings were confirmed and expanded by morphological data. The current findings shed new light on the mutually cooperative interplay between cells and the extracellular environment in the aging SM. These data open the door for a better understanding of the mechanisms modulating myocellular behavior in aging (e.g., by altering mechano-sensing stimuli as well as signaling pathways) and their contribution to age-dependent muscle dysfunction.

Glioblastoma is a lethal primary brain tumor lacking effective therapy. The secluded onset site, combined with the infiltrative properties of this tumor, require novel targeted therapies. In this scenario, the use of oncolytic viruses retargeted to glioblastoma cells and able to spread across the tumor cells represent an intriguing treatment strategy. Here, we tested the specificity, safety and efficacy of R-613, the first oncolytic HSV fully retargeted to EGFRvIII, a variant of the epidermal growth factor receptor carrying a mutation typically found in glioblastoma. An early treatment with R-613 on orthotopically transplanted EGFRvIII-expressing human glioblastoma significantly increased the median survival time of mice. In this setting, the growth of human glioblastoma xenotransplants was monitored by a secreted luciferase reporter and showed that R-613 is able to substantially delay the development of the tumor masses. When administered as late treatment to a well-established glioblastomas, R-613 appeared to be less effective. Notably the uninfected tumor cells derived from the explanted tumor masses were still susceptible to R-613 infection ex vivo, thus suggesting that multiple treatments could enhance R-613 therapeutic efficacy, making R-613 a promising oncolytic HSV candidate for glioblastoma treatment.

Natural elicitors from macroalgae may affect plant secondary metabolites. Ulvan is a sulfated heteropolysaccharide extracted from green seaweed, acting as both a plant biotic protecting agent, and a plant elicitor, leading to the synthesis of signal molecules. In this work, the aqueous extract of Ulva intestinalis L., mainly composed of ulvan, was used as foliar-spraying treatment and its eliciting effect was investigated in basil (Ocimum basilicum L.) and parsley (Petroselinum crispum L.). Antioxidant metabolites (polyphenols and carotenoids), volatile compounds (both in headspace emissions and hydrodistilled essential oils), and hormones (jasmonic acid, salicylic acid, salicylic acid 2-O-β-D-glucoside, abscisic acid, and azelaic acid) were quantified. The foliar-spraying treatment with U. intestinalis extract increased salicylic acid and its β-glucoside in parsley; in basil, it induced the accumulation of jasmonic and abscisic acids, indicating the presence of a priming effect. In basil, the elicitation caused a change of the essential oil (EO) chemotype from methyl eugenol/eugenol to epi-α-cadinol and increased sesquiterpenes. In parsley EO it caused a significant accumulation of 1,3,8-p-menthatriene, responsible of the typical “parsley-like” smell. In both species, the phenylpropanoids decreased in headspace and EO compositions, while the salicylic acid concentration increased; this could indicate a primarily defensive response to U. intestinalis extract. Due to the evidenced significant biological activity, U. intestinalis extract used as an elicitor may represent a suitable tool to obtain higher amounts of metabolites for optimizing plant flavor metabolites.

Both static and dynamic ambiguous stimuli representing human bodies that perform unimanual or unipedal movements are usually interpreted as right-limbed rather than left-limbed, suggesting that human observers attend to the right side of others more than the left one. Moreover, such a bias is stronger when static human silhouettes are presented in the RVF (right visual field) than in the LVF (left visual field), which might represent a particular instance of embodiment. On the other hand, hemispheric-specific rotational biases, combined with the well-known bias to perceive forward-facing figures, could represent a confounding factor when accounting for such findings. Therefore, we investigated whether the lateralized presentation of an ambiguous rotating human body would affect its perceived handedness/footedness (implying a role of motor representations), its perceived spinning direction (implying a role of visual representations), or both. To this aim, we required participants to indicate the perceived spinning direction (which also unveils the perceived handedness/footedness) of ambiguous stimuli depicting humans with an arm or a leg outstretched. Results indicated that the lateralized presentation of the stimuli affected both their perceived limb laterality (a larger number of figures being interpreted as right-limbed in the RVF than in the LVF) and their perceived spinning direction (a larger number of figures being interpreted as spinning clockwise in the LVF than in the RVF). However, the hemifield of presentation showed a larger effect size on the perceived spinning direction than on the perceived limb laterality. Therefore, as we already proposed, the implicit representation of others’ handedness seems to be affected more by visual than by motor processes during the perception of ambiguous human silhouettes.

Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.

In this pilot study, ethosomes and transethosomes were investigated as potential delivery systems for cholecalciferol (vitamin D3), whose deficiency has been correlated to many disorders such as dermatological diseases, systemic infections, cancer and sarcopenia. A formulative study on the influence of pharmaceutically acceptable ionic and non-ionic surfactants allowed the preparation of different transethosomes. In vitro cytotoxicity was evaluated in different cell types representative of epithelial, connective and muscle tissue. Then, the selected nanocarriers were further investigated at light and transmission electron microscopy to evaluate their uptake and intracellular fate. Both ethosomes and transethosomes proven to have physicochemical properties optimal for transdermal penetration and efficient vitamin D3 loading; moreover, nanocarriers were easily internalized by all cell types, although they followed distinct intracellular fates: ethosomes persisted for long times inside the cytoplasm, without inducing subcellular alteration, while transethosomes underwent rapid degradation giving rise to an intracellular accumulation of lipids. These basic results provide a solid scientific background to in vivo investigations aimed at exploring the efficacy of vitamin D3 transdermal administration in different experimental and pathological conditions.

Fractional-order controllers have gained significant research interest in various practical applications due to the additional degrees of freedom offered in their tuning process. The main contribution of this work is the analog implementation, for the first time in the literature, of a fractional-order controller with a transfer function that is not directly constructed from terms of the fractional-order Laplacian operator. This is achieved using Padé approximation, and the resulting integer-order transfer function is implemented using operational transconductance amplifiers as active elements. Post-layout simulation results verify the validity of the introduced procedure.

Una de les aportacions principals de les geografies dels nens i de les nenes a la disciplina geogràfica ha estat la inclusió dels infants com a actors de creació o producció d’espai, ja que l’utilitzen i el viuen segons les seves necessitats i els seus criteris, i ho fan de manera legítima. Per tant, l’escola ha de beneficiar-se d’aquest coneixement i connectar-lo amb la manera d’ensenyar geografia, perquè l’ús de l’espai per part de les criatures sigui més ben comprès per elles mateixes. L’objectiu del present article és connectar aquests dos àmbits que han caminat de manera paral·lela a partir de l’elaboració d’una proposta sobre com es poden acostar les geografies de la infància a la didàctica de la geografia, per tal que aquesta última incorpori la recerca i la conceptualització produïda per la primera. Els quatre pilars d’aquest model són: considerar que els nens i les nenes són agents socioespacials, tenir en compte la manera com es du a terme l’apropiació de l’espai a la infància, atendre les primeres representacions de l’experiència espacial i conèixer de quina manera són els llocs d’infància de l’alumnat que s’educa.

Abstract Background Phosphodiesterases (PDE) are a superfamily of enzymes that hydrolyse cyclic nucleotides (cAMP/cGMP), signal molecules in transduction pathways regulating crucial aspects of cell life. PDEs regulate the intensity and duration of the cyclic nucleotides signal modulating the downstream biological effect. Due to this critical role associated with the extensive distribution and multiplicity of isozymes, the 11 mammalian families (PDE1 to PDE11) constitute key therapeutic targets. PDE5, one of these cGMP-specific hydrolysing families, is the molecular target of several well known drugs used to treat erectile dysfunction and pulmonary hypertension. Kluyveromyces lactis, one of the few yeasts capable of utilizing lactose, is an attractive host alternative to Saccharomyces cerevisiae for heterologous protein production. Here we established K. lactis as a powerful host for the quantitative production of the murine PDE5 isoforms. Results Using the promoter of the highly expressed KlADH3 gene, multicopy plasmids were engineered to produce the native and recombinant Mus musculus PDE5 in K. lactis. Yeast cells produced large amounts of the purified A1, A2 and A3 isoforms displaying Km, Vmax and Sildenafil inhibition values similar to those of the native murine enzymes. PDE5 whose yield was nearly 1 mg/g wet weight biomass for all three isozymes (30 mg/L culture), is well tolerated by K. lactis cells without major growth deficiencies and interferences with the endogenous cAMP/cGMP signal transduction pathways. Conclusions To our knowledge, this is the first time that the entire PDE5 isozymes family containing both regulatory and catalytic domains has been produced at high levels in a heterologous eukaryotic organism. K. lactis has been shown to be a very promising host platform for large scale production of mammalian PDEs for biochemical and structural studies and for the development of new specific PDE inhibitors for therapeutic applications in many pathologies.

We consider the large order behavior of the perturbative expansion of the scalar φ4 field theory in terms of a perturbative expansion around an instanton solution. We have computed the series of the free energy up to two-loop order in two and three dimension. Topologically there is only an additional Feynman diagram with respect to the previously known one dimensional case, but a careful treatment of renormalization is needed. The propagator and Feynman diagrams were expressed in a form suitable for numerical evaluation. We then obtained explicit expressions summing over O(103) distinct eigenvalues determined numerically with the corresponding eigenfunctions.

The climate change vulnerability discourse in the Maldives coexists with a pervasive set of critical environmental factors of significance to the socio-environmental systems of small peripheral islands. This implies the need to strike a balance between global challenges associated with environmental processes at the supra-national scale and the adjustments and strategies implemented at the local scale in response to change. The current paper offers a discussion of this dialectic, in reference to both the broader contemporary debate in island studies, and the political and environmental context of the Maldives. We first outline the international scenario, and then go on, in the second part of the paper, to provide a reading of environmental policy on these islands. We argue that emphasizing the country’s environmental vulnerability has reinforced a ‘lexicon of risk’ within the environmental discourse and that, in recent years, this narrative has been one of the main forces driving the construction of contemporary Maldivian ‘nation-ness’.

This report documents an uncommon case of choristomatous cervical polyp-containing fat tissue. The patient was a 24-year-old female who presented with irregular intermenstrual bleeding. On examination, a polypoid lesion with smooth outlines, measuring 1 cm in diameter was removed. Microscopic examination demonstrated abnormal fibrous stroma, devoid of endocervical glands, containing mature adipose tissue, and thick-walled blood vessels. The lesion was covered by a typical mature squamous cell outer lining. To the best of our knowledge, this is only the second report of an adipose tissue arising from the cervical wall. Further clinicopathologic considerations are needed to elucidate the origin of the fatty component in cervical polyps.

An adult male Eurasian otter, found dead on the roadside, was submitted for post-mortem examination in April 2014 at the Veterinary Pathology Unit of the Faculty of Veterinary Medicine of Teramo, as part of the RECAL [RECovery and post mortem Analysis of Eurasian otters (Lutra lutra) in the National Park of Cilento, Vallo di Diano and Alburni (Salerno, Italy), and surrounding areas] project. Necropsy revealed an abundant hemothorax associated with multifocal, bilateral pulmonary contusions and lacerations, and a severe hemopericardium characterised by the presence of a wide blood clot in the intact pericardial sac. Two small laceration wounds of the left auricle were found at the base, along the atrioventricular groove, and on the outer free wall. Since myocardial and endocardial tissues showed no other gross and histopathological abnormalities, a left atrial appendage rupture resulting from a blunt chest trauma was diagnosed. Blunt traumatic cardiac rupture is a rarely reported, life-threatening condition in humans. To the best of our knowledge, this is the first report on a left atrial appendage rupture due to blunt chest trauma in veterinary literature. The possible occurrence of a cardiac rupture following a blunt thoracic injury should be taken into consideration in veterinary emergency care.

Whereas the role of observers' sex has already been addressed in research on embodied cognition, so far it has been neglected as regards laterality effects in embodied cognition. Here, we report further analyses of the data used in our paper “Hemispheric asymmetries in the processing of body sides: A study with ambiguous human silhouettes” [1], where participants had to indicate the perceived orientation of silhouettes with ambiguous front/back orientation and handedness presented in the right and left hemifield. Specifically, the variables examined in the associated paper (the number of right- and left-sided silhouettes perceived as front- and back-facing in each hemifield; the number of silhouettes perceived as right- and left-handed in each hemifield) are analyzed by also factoring in participant's sex). Moreover, data are provided and analyses are performed both for the total sample of participants and for the sample of right-handed participants only. For further details, as well as for the interpretation and discussion of the data, the reader is referred to the main article [1] and its Supplementary Material. Keywords: Handedness, Human body, Ambiguous figures, Divided visual field paradigm, Lateralized embodiment, Sex differences

This paper addresses a database collected and constructed as part of PhD research project on the north-western coast of the Dominican Republic. The PhD was part of the ERC Synergy Grant NEXUS 1492: New World Encounters in a Globalizing World. The database was collected during fieldwork campaigns between 2014 and 2015. Fieldwork consisted of a regional survey, material culture registry and collection, test pit excavation, and processing relevant environmental variables. The archaeological data consists of a record of 102 archaeological sites, the material culture associated with them (lithic, shell and coral objects, shell mollusk species), and the relationship between site location and a set of relevant environmental variables used for statistical analysis. This database is one of the only open access archaeological databases available at the moment in the Caribbean and can be reused by any Caribbean archaeologist working in the Greater Antilles. Funding statement: This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement nº 319209, under the direction of Prof. Dr. Corinne Hofman.

Mothers usually cradle their infants to the left of their body midline, an asymmetry that seems to be a typically female lateral preference. This bias is deemed to be an evolutionary facilitator of communication between cradling and cradled individuals and is believed to be strongly related to hemispheric specialization for complex socio-affective behaviors. Thus, left cradling might facilitate affective interactions in females with typical brain organization, probably due to a right-hemisphere dominance for social attachment. In this study, we investigated cradling-side preferences in 288 young females as a function of their attachment styles to parents and partners. A left-cradling bias was more frequent in participants experiencing positive relationships with their mother and romantic partners. These findings indicate that the left-cradling bias may be associated with high-quality social attachment behaviors in females and, therefore, can be considered as a natural index of socio-emotional attunement between the cradling and cradled individuals.

Transmission electron microscopy is the technique of choice to visualize the spatial relationships between nanoconstructs and cells and especially to monitor the uptake process of nanomaterials. It is therefore crucial that the cell surface be preserved in its integrity, to obtain reliable ultrastructural evidence: the plasmalemma represents the biological barrier the nanomaterials have to cross, and the mode of membrane-nanoconstruct interaction is responsible for the intracellular fate of the nanomaterials. In this paper, we describe a simple and inexpensive method to process cell monolayers for ultrastructural morphology and immunocytochemistry, ensuring consistent preservation of the cell surface and of the occurring interactions with nanoparticles of different chemical composition.

Introduction. There is a paucity of information about risk behaviors in adolescents with chronic kidney disease (CKD). We designed this study to assess the prevalence of risk behaviors among teens with CKD in the United States and to investigate any associations between risk behavior and patient or disease characteristics. Methods. After informed consent, adolescents with CKD completed an anonymous, confidential, electronic web-based questionnaire to measure risk behaviors within five domains: sex, teen driving, alcohol and tobacco consumption, illicit drug use, and depression-related risk behavior. The reference group was composed of age-, gender-, and race-matched US high school students. Results. When compared with controls, teens with CKD showed significantly lower prevalence of risk behaviors, except for similar use of alcohol or illicit substances during sex (22.5% vs. 20.8%, p=0.71), feeling depressed for ≥2 weeks (24.3% vs. 29.1%, p=0.07), and suicide attempt resulting in injury needing medical attention (36.4% vs. 32.5%, p=0.78). Furthermore, the CKD group had low risk perception of cigarettes (28%), alcohol (34%), marijuana (50%), and illicit prescription drug (28%). Use of two or more substances was significantly associated with depression and suicidal attempts (p

El refinanciamiento de pasivo es una de las prácticas más utilizadas por las corporaciones para hacer frente al vencimiento de obligaciones de corto plazo. Sin una adecuada gestión de activos y pasivos (ALM por su sigla en inglés), las entidades se ven obligadas a refinanciar en condiciones de mercado desfavorables, por ejemplo, altas tasas de interés. Si bien, la gestión de riesgo de refinanciamiento a través de ALM es un tema bien estudiado y aplicado en el sector financiero, en las empresas no financieras su uso es escaso. El presente trabajo establece una metodología de análisis del riesgo de refinanciamiento, para empresas no financieras, por medio de la cuantificación de exposiciones utilizando información públicamente disponible en los Estados Financieros. Específicamente, se proponen dos métricas: (1) el descalce estructural de plazos de balance, que aproxima cuán probable es que una empresa deba refinanciar pasivo, y (2) el Patrimonio at Risk (PaR), el cual mide la mayor pérdida esperada de valor patrimonial al refinanciar en condiciones de mercado desfavorables. Las referidas métricas son debidamente validadas a través de análisis empírico. Para ello, se utiliza una muestra de 163 empresas chilenas cotizadas en Bolsa y se muestra que las métricas propuestas explican más fuertemente la probabilidad de que una empresa refinancie pasivo, en comparación con otra medida establecida en la literatura.

Purpose: The aim of this study was to investigate the relationship between the energy cost of running (Cr) and speed and its mechanical determinants by comparing running in normal [100% body weight (BW)] and reduced (20% and 60% BW) gravity conditions at several speeds (2.25, 3.17, 4.08, and 5.00 m·s−1) in experienced runners.Methods: Twelve experienced runners (24.6 ± 5.4 year) ran on an AlterG treadmill in a partially randomized order at the four running speeds and at the three gravity conditions in order to assess Cr, spatiotemporal parameters, spring-mass characteristics and elastic energy (EL) during running.Results: For the three gravity conditions, the speed-Cr per kg of body mass relationship was curvilinear (significant speed effect: P < 0.001) and was significantly downward shifted with reduced gravity (100%>60%>20% BW; P < 0.001). EL, expressed in J·step−1, was significantly higher at 100% BW than at 60 and 20% BW and at 60% BW than at 20% BW (significant gravity effect: P < 0.001) with a significant increase in EL per step at faster speeds for the 3 gravity conditions (P < 0.001). EL, expressed in J·kg−1·m−1, was significantly downward shifted with gravity (100%>60%>20% BW; P < 0.001), with no significant speed effect (P = 0.39).Conclusions: Our findings showed that, for the three gravity conditions, the speed-Cr relationship was curvilinear, and the optimization of the stretch-shortening cycle and muscle activation in the muscle-tendon unit may be involved to explain these U-shaped relationships, especially at normal terrestrial gravitational conditions (100% BW). The U-shaped speed-Cr per kg of the body mass relationship was shifted downward in hypogravity conditions, which was characterized by decreased EL compared to 100% BW. These mechanisms may contribute to the less than proportional decrease in Cr per kg of body mass relative to gravity.

The high-resolution images provided by the electron microscopy has constituted a limitless source of information in any research field of life and materials science since the early Thirties of the last century. Browsing the scientific literature, electron microscopy was especially popular from the 1970’s to 80’s, whereas during the 90’s, with the advent of innovative molecular techniques, electron microscopy seemed to be downgraded to a subordinate role, as a merely descriptive technique. Ultrastructural histochemistry was crucial to promote the Renaissance of electron microscopy, when it became evident that a precise localization of molecules in the biological environment was necessary to fully understand their functional role. Nowadays, electron microscopy is still irreplaceable for ultrastructural morphology in basic and applied biomedical research, while the application of correlative light and electron microscopy and of refined ultrastructural histochemical techniques gives electron microscopy a central role in functional cell and tissue biology, as a really unique tool for high-resolution molecular biology in situ.

We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario.

The United Nations Decade on Education for Sustainable Development (ESD) expanded the epistemological and methodological debate on sustainability and education. Currently, ESD encompasses a broad spectrum of socio-political issues (including global citizenship and social justice), while “place-bonding” is seen as key to fostering citizen advocacy in local communities and enhancing “children’s lived experiences of local issues”. Herein, we emphasize both the political and the pedagogical value of this perspective, arguing that ESD bears the potential to overcome “universal vs. individual” tensions and dichotomies. Our line of reasoning is that the “capabilities approach” (CA), although it did not originally focus on children, can offer a useful theoretical framework in support of ESD, thanks to its multidimensional nature and focus on the concrete agency of individuals. Accordingly, we see the CA as playing a key role in bridging the gap between universal prescriptions, which disregard the specificity of the actors involved, as well as the peculiar nature of their social environment and its context-specific needs or constraints. We supplement this theoretical discussion by presenting “The Flying Carpet”, an ongoing community-based education project that has elicited the active involvement of over one hundred 11–13 year old students in an urban regeneration project in a municipal district of Milan.