Social robotics as an adjuvant during the hospitalization process in pediatric oncology patients.

OBJECTIVE: To describe the experience of implementing social robotics as an adjuvant during the hospitalization process in pediatric oncology patients. METHODS: Before and after cohort study, applying an intervention with the Lego Mindstorms EV3 kit in patients between 8 and 17 years old that are hospitalized with a cancer diagnosis. We excluded patients from the intensive care unit or when their treating physician recommended so. The intervention consisted of a three-phase workshop: an open architecture story, building a car robot using the Lego Mindstorm EV3 kit, and cooperative playing activities such as races and passing obstacles. RESULTS: Thirteen patients received the intervention with robotic lego. The median age was 15 years (IQR = 3), and 84.6% of the population (n = 11) were male. We found significant improvement in the language (topic management p = .011 and communicative intention p = .034). Other characteristics improved, but not significantly (self-care activities index, catching). No adverse events occurred during the intervention. CONCLUSIONS: The results of this pilot study suggest that implementing social robotics during hospitalization in children with cancer is a therapeutic adjuvant and safe intervention that promotes better communication, self-care, and a physical activity improvement. For future studies, the impact of this intervention could be measured in hospitalized pediatric cancer patients.

N-Acetylcistein for thrombotic thrombocytopenic purpura: an observational case series study.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. N-Acetylcysteine (NAC) rapidly degrades ultra-large von Willebrand factor multimers by disrupting the disulfide bonds. We report a series of twelve consecutive patients diagnosed with acquired TTP successfully treated with high-dose NAC (150 mg/kg/day) in combination with plasma exchange and steroids. Eight patients also received rituximab. Two patients presented refractory TTP. All patients achieved a quick clinical response in a median time of 5.5 days after starting NAC and are alive after a median follow-up of 29 months. The treatment was feasible and well tolerated. These data provide further evidence of the potential benefit and safety of adding NAC to the standard of care.

Education by a social robot on nutrition and catheter care in pediatric oncology patients.

PURPOSE: To improve knowledge on nutrition and catheter care in children with cancer by an educational intervention with a social robot. METHODS: We conducted a cohort study on pediatric cancer patients in a high complexity Hospital in Bogotá, Colombia. We included 14 patients (8-17 years old) who underwent an educational intervention with the help of a humanoid robot (Nao V6). The robot was programmed to transmit educational messages about self-care in feeding and using the central venous catheter. A survey with yes-no questions was administered before and after the intervention. RESULTS: We found an improvement in understanding of the subject matter related to nutrition and catheter care, when comparing the knowledge on topics before and after the educational intervention (p < .001). CONCLUSION: Education by a social robot on nutrition and catheter care showed a positive effect on children's knowledge on these topics. Therefore, it potentially decreases the risk of poor feeding habits and inadequate central venous catheter management, and improves adherence to recommendations and quality of life.

Near-Room-Temperature Magnetoelectric Coupling via Spin Crossover in an Iron(II) Complex.

Magnetoelectric coupling is achieved near room temperature in a spin crossover FeII molecule-based compound, [Fe(1bpp)2 ](BF4 )2 . Large atomic displacements resulting from Jahn-Teller distortions induce a change in the molecule dipole moment when switching between high-spin and low-spin states leading to a step-wise change in the electric polarization and dielectric constant. For temperatures in the region of bistability, the changes in magnetic and electrical properties are induced with a remarkably low magnetic field of 3 T. This result represents a successful expansion of magnetoelectric spin crossovers towards ambient conditions. Moreover, the observed 0.3-0.4 mC m-2 changes in the H-induced electric polarization suggest that the high strength of the coupling obtained via this route is accessible not just at cryogenic temperatures but also near room temperature, a feature that is especially appealing in the light of practical applications.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB, CD16B) deficiency in patients with blood and immune system disorders.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB) deficiency is present in ˜0·05% of the general population. Among our patients, FcγRIIIB deficiency was less frequent in those with immune-system disorders (one of 1815 patients, 0·05%) than in those with blood disorders (nine of 2147 patients, 0·42%, P = 0·023): mainly primary immune thrombocytopenia (4·34%), therapy related myeloid neoplasms (1·16%) and myelodysplastic syndrome with excess blasts (1·28%). Four of the nine (44·4%) patients with blood disorders were diagnosed with or quickly evolved to acute myeloid leukaemia (AML), suggesting that FcγRIIIB deficiency could be an adverse prognostic factor for progression to AML that should be confirmed in large multicentre studies.

Phosphoserine inhibits neighboring arginine methylation in the RKS motif of histone H3.

The effects of phosphorylation of histone H3 at serine 10 have been studied in the context of other posttranslational modifications such as lysine methylation. We set out to investigate the impact of phosphoserine-10 on arginine-8 methylation. We performed methylation reactions using peptides based on histone H3 that contain a phosphorylated serine and compared the extent of arginine methylation with unmodified peptides. Results obtained via fluorography indicate that peptides containing a phosphorylated serine-10 inhibit deposition of methyl groups to arginine-8 residues. To further explore the effects of phosphoserine on neighboring arginine residues, we physically characterized the non-covalent interactions between histone H3 phosphoserine-10 and arginine-8 using 31P NMR spectroscopy. A salt bridge was detected between the negatively charged phosphoserine-10 and the positively charged unmodified arginine-8 residue. This salt bridge was not detected when arginine-8 was symmetrically dimethylated. Finally, molecular simulations not only confirm the presence of a salt bridge but also identify a subset of electrostatic interactions present when arginine is replaced with alanine. Taken together, our work suggests that the negatively charged phosphoserine maximizes its interactions. By limiting its exposure and creating new contacts with neighboring residues, it will inhibit deposition of neighboring methyl groups, not through steric hindrance, but by forming intrapeptide interactions that may mask substrate recognition. Our work provides a mechanistic framework for understanding the role of phosphoserine on nearby amino acid residues and arginine methylation.

Acute basilar artery occlusion (BAO): a pictorial review of multimodal imaging findings.

Acute basilar artery occlusion (BAO) is an uncommon cause of stroke; however, it constitutes a serious medical emergency and is associated with elevated mortality rates as well as unfavorable functional outcomes. This is especially true when it is not rapidly diagnosed, and the initiation of reperfusion therapies is delayed. Its etiology is mainly embolic or atherosclerotic, and it often presents with non-specific signs and symptoms (e.g., vertigo, cephalalgia, reduced consciousness, or hemiparesis) that can simulate an anterior circulation stroke. Therefore, obtaining imaging studies that include computed tomography (CT), computed tomography angiography (CTA), and diffusion-weighted magnetic resonance imaging (DWI MRI) as part of the diagnostic approach is crucial to make an accurate diagnosis. The main pillar of acute BAO treatment is early recanalization using intravenous thrombolysis, mechanical thrombectomy, or bridging therapy, in which both methods are used. This pictorial essay illustrates the essential role that multimodal imaging plays in the prompt diagnosis, management, and overall outcome of patients with acute BAO.

Novel non-resorbable polymeric-nanostructured scaffolds for guided bone regeneration.

OBJECTIVE: The aim of this study was to evaluate the bone-regeneration efficiency of novel polymeric nanostructured membranes and the effect of zinc, calcium, titanium, and bone morpho-protein loading on membranes, through an in vivo rabbit model. MATERIAL AND METHODS: Nanostructured membranes of methylmethacrylate were loaded with zinc, calcium, TiO2 nanoparticles, and bone-morphogenetic protein (BMP). These membranes covered the bone defects prepared on the skulls of six rabbits. Animals were sacrificed 6 weeks after surgery. Micro computed tomography was used to evaluate bone architecture through BoneJ pluging and ImageJ script. Three histological processing of samples, including von Kossa silver nitrate, toluidine blue, and fluorescence by the deposition of calcein were utilized. RESULTS: Zn-membranes (Zn-Ms) promoted the highest amount of new bone and higher bone perimeter than both unloaded and Ti-membranes (Ti-Ms). Ca-membranes (Ca-Ms) attained higher osteoid perimeter and bone perimeter than Zn-Ms. The skeleton analysis showed that Zn-Ms produced more branches and junctions at the trabecular bone than BMP-loaded membranes (BMP-Ms). Samples treated with Ti-Ms showed less bone formation and bony bridging processes. Both Zn-Ms and Ca-Ms achieved higher number of osteoblasts than the control group. BMP-Ms and Ca-Ms originated higher number of blood vessels than Ti-Ms and control group. CONCLUSIONS: Zn incorporation in novel nanostructured membranes provided the highest regenerative efficiency for bone healing at the rabbit calvarial defects. CLINICAL RELEVANCE: Zn-Ms promoted osteogenesis and enhanced biological activity, as mineralized and osteoid new bone with multiple interconnected ossified trabeculae appeared in close contact with the membrane.

Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival.

BACKGROUND: Through several not-fully-characterised moonlighting functions, translation elongation factor eEF1A2 is known to provide a fitness boost to cancer cells. Furthermore, eEF1A2 has been demonstrated to confer neoplastic characteristics on preneoplastic, nontumourigenic precursor cells. We have previously shown that eEF1A2 is the target of plitidepsin, a marine drug currently in development for cancer treatment. Herein, we characterised a new signalling pathway through which eEF1A2 promotes tumour cell survival. METHODS: Previously unknown binding partners of eEF1A2 were identified through co-immunoprecipitation, high-performance liquid chromatography-mass spectrometry and proximity ligation assay. Using plitidepsin to release eEF1A2 from those protein complexes, their effects on cancer cell survival were analysed in vitro. RESULTS: We uncovered that double-stranded RNA-activated protein kinase (PKR) is a novel eEF1A2-interacting partner whose pro-apoptotic effect is hindered by the translation factor, most likely through sequestration and inhibition of its kinase activity. Targeting eEF1A2 with plitidepsin releases PKR from the complex, facilitating its activation and triggering a mitogen-activated protein kinase signalling cascade together with a nuclear factor-κB-dependent activation of the extrinsic apoptotic pathway, which lead to tumour cell death. CONCLUSIONS: Through its binding to PKR, eEF1A2 provides a survival boost to cancer cells, constituting an Achilles heel that can be exploited in anticancer therapy.

Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells.

BACKGROUND: Vascular supply of tumors is one of the main targets for cancer therapy. Here, we investigated if plocabulin (PM060184), a novel marine-derived microtubule-binding agent, presents antiangiogenic and vascular-disrupting activities. METHODS: The effects of plocabulin on microtubule network and dynamics were studied on HUVEC endothelial cells. We have also studied its effects on capillary tube structures formation or destabilization in three-dimensional collagen matrices. In vivo experiments were performed on different tumor cell lines. RESULTS: In vitro studies show that, at picomolar concentrations, plocabulin inhibits microtubule dynamics in endothelial cells. This subsequently disturbs the microtubule network inducing changes in endothelial cell morphology and causing the collapse of angiogenic vessels, or the suppression of the angiogenic process by inhibiting the migration and invasion abilities of endothelial cells. This rapid collapse of the endothelial tubular network in vitro occurs in a concentration-dependent manner and is observed at concentrations lower than that affecting cell survival. The in vitro findings were confirmed in tumor xenografts where plocabulin treatment induced a large reduction in vascular volume and induction of extensive necrosis in tumors, consistent with antivascular effects. CONCLUSIONS: Altogether, these data suggest that an antivascular mechanism is contributing to the antitumor activities of plocabulin.

Disruptive chemicals, senescence and immortality.

Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.

Molecular and functional characterization of allantoate amidohydrolase from Phaseolus vulgaris.

Allantoate degradation is an essential step for recycling purine-ring nitrogen in all plants, but especially in tropical legumes where the ureides allantoate and allantoin are the main compounds used to store and transport the nitrogen fixed in nodules. Two enzymes, allantoate amidohydrolase (AAH) and allantoate amidinohydrolase (allantoicase), could catalyze allantoate breakdown, although only AAH-coding sequences have been found in plant genomes, whereas allantoicase-related sequences are restricted to animals and some microorganisms. A cDNA for AAH was cloned from Phaseolus vulgaris leaves. PvAAH is a single-copy gene encoding a polypeptide of 483 amino acids that conserves all putative AAH active-site domains. Expression and purification of the cDNA in Nicotiana benthamiana showed that the cloned sequence is a true AAH protein that yields ureidoglycine and ammonia, with a Km of 0.46 mM for allantoate. Optimized in vitro assay, quantitative RT-PCR and antibodies raised to the PvAAH protein were used to study AAH under physiological conditions. PvAAH is ubiquitously expressed in common bean tissues, although the highest transcript levels were found in leaves. In accordance with the mRNA expression levels, the highest PvAAH activity and allantoate concentration also occurred in the leaves. Comparison of transcript levels, protein amounts and enzymatic activity in plants grown with different nitrogen sources and upon drought stress conditions showed that PvAAH is regulated at posttranscriptional level. Moreover, RNAi silencing of AAH expression increases allantoate levels in the transgenic hairy roots, indicating that AAH should be the main enzyme involved in allantoate degradation in common bean.

Novel Ti surface coated with PVA hydrogel and chitosan nanoparticles with antibacterial drug release: An experimental in vitro study.

OBJECTIVES: The aims of this study were to design a novel titanium surface coated with a PVA hydrogel matrix and chitosan-based nanoparticles and to investigate the antibiotic release and its ability to inhibit microbial activity. METHODS: Two drug delivery systems were developed and mixed. Chitosan-based nanoparticles (NP) and a polyvinyl alcohol film (PVA). The size, ζ-potential, stability, adhesive properties, and encapsulation profile of NP, as well as the release kinetics of drug delivery systems and their antimicrobial ability of PVA and PVANP films, were studied on Ti surfaces. The systems were loaded with doxycycline, vancomycin, and doxepin hydrochloride. RESULTS: Nanoparticles presented a ζ-potential greater than 30 mV for 45 days and the efficiency drug encapsulation was 26.88% ± 1.51% for doxycycline, 16.09% ± 10.24% for vancomycin and 17.57% ± 11.08% for doxepin. In addition, PVA films were loaded with 125 µg/mL of doxycycline, 125 µg/mL of vancomycin, and 100 µg/mL of doxepin. PVANP-doxycycline achieved the antibacterial effect at 4 h while PVA-doxycycline maintained its effect at 24 h.

Clinical comparison of marginal fit of ceramic inlays between digital and conventional impressions.

PURPOSE: The aim of this stuldy was to compare the clinical marginal fit of CAD-CAM inlays obtained from intraoral digital impression or addition silicone impression techniques. MATERIALS AND METHODS: The study included 31 inlays for prosthodontics purposes of 31 patients: 15 based on intraoral digital impressions (DI group); and 16 based on a conventional impression technique (CI group). Inlays included occlusal and a non-occlusal surface. Inlays were milled in ceramic. The inlay-teeth interface was replicated by placing each inlay in its corresponding uncemented clinical preparation and taking interface impressions with silicone material from occlusal and free surfaces. Interface analysis was made using white light confocal microscopy (WLCM) (scanning area: 694 × 510 µm2) from the impression samples. The gap size and the inlay overextension were measured from the microscopy topographies. For analytical purposes (i.e., 95-%-confidence intervals calculations and P-value calculations), the procedure REGRESS in SUDAAN was used to account for clustering (i.e., multiple measurements). For p-value calculation, the log transformation of the dependent variables was used to normalize the distributions. RESULTS: Marginal fit values for occlusal and free surfaces were affected by the type of impression. There were no differences between surfaces (occlusal vs. free). Gap obtained for DI group was 164 ± 84 µm and that for CI group was 209 ± 104 µm, and there were statistical differences between them (p = .041). Mean overextension values were 60 ± 59 µm for DI group and 67 ± 73 µm for CI group, and there were no differences between then (p = .553). CONCLUSION: Digital impression achieved inlays with higher clinical marginal fit and performed better than the conventional silicone materials.

PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma.

PIM serine/threonine kinases are overexpressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa-associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.

Local inhibition of nitrogen fixation and nodule metabolism in drought-stressed soybean.

Drought stress is a major factor limiting symbiotic nitrogen fixation (NF) in soybean crop production. However, the regulatory mechanisms involved in this inhibition are still controversial. Soybean plants were symbiotically grown in a split-root system (SRS), which allowed for half of the root system to be irrigated at field capacity while the other half remained water deprived. NF declined in the water-deprived root system while nitrogenase activity was maintained at control values in the well-watered half. Concomitantly, amino acids and ureides accumulated in the water-deprived belowground organs regardless of transpiration rates. Ureide accumulation was found to be related to the decline in their degradation activities rather than increased biosynthesis. Finally, proteomic analysis suggests that plant carbon metabolism, protein synthesis, amino acid metabolism, and cell growth are among the processes most altered in soybean nodules under drought stress. Results presented here support the hypothesis of a local regulation of NF taking place in soybean and downplay the role of ureides in the inhibition of NF.

New media for classical coordination chemistry: phase transfer of Werner and related polycations into highly nonpolar fluorous solvents.

Optimized procedures for the previously reported conversions of 1,3-diiodobenzene and perfluorohexyliodide (Rf6I; copper, DMSO, 140 °C) to 1,3-C6H4(Rf6)2 (3; 86-70%) and 3 to Br(3,5-C6H3(Rf6)2 (2; NBS, H2SO4/CF3CO2H; 88-75%) are described. The latter is converted (t-BuLi, BCl3) to the "fluorous BArf" salt NaB(3,5-C6H3(Rf6)2)4 (1 or NaBArf6; 77-70%), as given earlier. When orange aqueous solutions of [Co(en)3]Cl3 (en = ethylenediamine) are treated with perfluoro(methylcyclohexane) (PFMC) solutions of 1 (1:3 mol ratio), the aqueous phase decolorizes and [Co(en)3](BArf6)3 can be isolated from the fluorous phase (96%). Similar reactions with the trans-1,2-cyclohexanediamine analogue [Co(R,R-chxn)3]Cl3 and [Ru(bipy)3]Cl2 give [Co-(R,R-chxn)3](BArf6)3 (92%) and [Ru(bipy)3](BArf6)2 (95%). All of these salts are isolated as hydrates and exhibit toluene/PFMC partition coefficients of ≤1:≥99, establishing that the anion BArf6(-) can efficiently transport polar polycations into highly nonpolar fluorous phases. When equal volumes of CH2Cl2 and PFMC are charged with the "nonfluorous" BArf (B(3,5-C6H3-(CF3)2)4) salt [Co(en)3](BArf)3 and 3.0 equiv of the fluorous salt NaBArf6, the cobalt trication partitions predominantly into the fluorous phase (64:36). The arene 2 crystallizes in a polar space group (tetragonal, I4, Z = 8) with fluorous and nonfluorous domains and all eight bromine atoms located essentially on one face of the unit cell.

Effect of hygroscopic expansion of resin filling on interfacial gap and sealing: a confocal microscopy study.

PURPOSE: To measure dimensional changes due to hygroscopic expansion and their effect on interface gaps and sealing in four light-cured restorative materials using an original confocal microscopic methodology. MATERIALS AND METHODS: The materials tested were an ormocer (Admira [Voco]), a compomer (Dyract AP [Dentsply]), a hybrid composite (Spectrum [Dentsply]), and a nanohybrid composite (Esthet·X [Dentsply]). Water sorption was evaluated by weighing material disks after immersion. Hygroscopic expansion was measured from volumetric variations of material fillings in cylindrical cavities in dentin slices; the interfacial gap size was obtained from the same cavities using a novel confocal microscopic method. Microleakage was evaluated in cavities prepared in extracted third molars. Measurements followed water immersion for 24 h, 1 week, 4 weeks, and 8 weeks. A factorial ANOVA, the Student Newman Keuls test for post-hoc comparisons, the Student's t-test, and the Pearson test were used for the statistical analysis (p < 0.05). RESULTS: Positive correlations were found among water sorption, hygroscopic expansion, and sealing. Hygroscopic expansion reduced post-polymerization interfacial gaps and improved cavity sealing. Dyract AP and Admira showed the highest water sorption, hygroscopic expansion, and gap size reduction. CONCLUSIONS: 1. The proposed methodology is valid to measure hygroscopic expansion and interfacial gap. 2. Water sorption and hygroscopic expansion are positively correlated, and hygroscopic expansion, gap size, and sealing are also positively correlated. 3. The adhesive influences the interfacial gap size and its variation after hygroscopic expansion. 4. Hygroscopic expansion reduces the interfacial gaps generated by polymerization shrinkage and improves cavity sealing.

How Confinement and Back to Normal Affected the Well-Being and Thus Sleep, Headaches and Temporomandibular Disorders.

The COVID-19 pandemic is having negative consequences not only for people's general health but also for the masticatory system. This article aimed to assess confinement and its new normal impact on well-being, sleep, headaches, and temporomandibular disorders (TMD). An anonymous survey was distributed to a Spanish university community. Participants completed a well-being index (WHO-5), a questionnaire related to sleep quality (the BEARS test), a headache diagnostic test (the tension type headache (TTH) and migraine diagnosis test), and the DC-TMD questionnaire. Questions were addressed in three scenarios: before confinement, during confinement, and the new normal. A total of 436 responses were collected (70% women, 30% men). A reduction in well-being and sleep quality was recorded. Respondents reported more TTH and migraines during and after confinement. Overall, confinement and return to normal did not increase TMD symptoms, and only minor effects were observed, such as more intense joint pain and a higher incidence of muscle pain in women during confinement. Reduced well-being is correlated with sleep quality loss, headaches, and TMD symptoms. This study provides evidence that pandemics and confinement might have had a negative impact on population health. Well-being was strongly affected, as were sleep quality, depression risk, TTH, and migraine frequency. In contrast, the temporomandibular joint and muscles showed more resilience and were only slightly affected.