Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children.

Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.

Extracorporeal versus intracorporeal anastomosis in laparoscopic right hemicolectomy for cancer.

INTRODUCTION: This study aimed at assessing the long-term oncological outcomes of intracorporeal ileocolic anastomosis (ICA) for laparoscopic right hemicolectomy for colon cancer compared with extracorporeal anastomosis (ECA). MATERIAL AND METHODS: We performed a retrospective analysis of 149 consecutive patients who underwent laparoscopic right hemicolectomy for colon cancer between January 2006 and December 2012. RESULTS: Eighty and 69 patients underwent intracorporeal and ECA, respectively. The two groups were demographically comparable. ICA exhibited a significantly shorter operative time (p < .0001), while local relapse and length of hospital stay did not significantly differ among the groups (p = .724 and .310, respectively). There was no significant difference in median number of retrieved lymph node. The overall survival and the disease-free survival at five years did not significantly differ among the groups. CONCLUSIONS: Intracorporeal ICA can reduce operative time and is associated with similar postoperative and long-term oncological outcomes compared to the ECA technique.

Circulating calprotectin as a supporting inflammatory marker in discriminating SARS-CoV-2 infection: an observational study.

OBJECTIVE AND DESIGN: Fecal calprotectin (CLP) is widely known for its detection in stools of patients with inflammatory bowel diseases (IBDs), to investigate the intestinal inflammatory status. Current research is promoting the circulating protein role as a systemic inflammatory marker. However, most studies report serum calprotectin analysis although plasma assay prevents its massive release by granulocytes. In this perspective, the ongoing SARS-CoV-2 pandemic deserves deployment of convenient and easy-to-dose markers that could reliably address the state of infection. METHODS: We analyzed serum circulating calprotectin (cCLP) levels in hospitalized COVID-19 patients and plasma cCLP levels from patients with suspected SARS-CoV-2 infection, then assessed negative or positive on molecular tests. RESULTS: Our results confirm a significant circulating calprotectin increase in infected subjects respect to controls, in serum and plasma. Moreover, plasma calprotectin has higher levels in suspected patients with positive SARS-CoV-2-RT-PCR, compared to suspected patients with negative SARS-CoV-2-RT-PCR. Furthermore, ROC curves results showed the circulating plasma calprotectin discriminatory ability to differentiate infected SARS-CoV-2 patients at a cutoff value greater than 131.3 ng/ml. CONCLUSIONS: Our data propose circulating calprotectin as a new, quantitative and predictive marker, which in addition to being an interesting generic inflammatory marker may provide important indications in SARS-CoV-2 infection.

Listening while reading promotes word learning from stories.

Reading and listening to stories fosters vocabulary development. Studies of single word learning suggest that new words are more likely to be learned when both their oral and written forms are provided, compared with when only one form is given. This study explored children's learning of phonological, orthographic, and semantic information about words encountered in a story context. A total of 71 children (8- and 9-year-olds) were exposed to a story containing novel words in one of three conditions: (a) listening, (b) reading, or (c) simultaneous listening and reading ("combined" condition). Half of the novel words were presented with a definition, and half were presented without a definition. Both phonological and orthographic learning were assessed through recognition tasks. Semantic learning was measured using three tasks assessing recognition of each word's category, subcategory, and definition. Phonological learning was observed in all conditions, showing that phonological recoding supported the acquisition of phonological forms when children were not exposed to phonology (the reading condition). In contrast, children showed orthographic learning of the novel words only when they were exposed to orthographic forms, indicating that exposure to phonological forms alone did not prompt the establishment of orthographic representations. Semantic learning was greater in the combined condition than in the listening and reading conditions. The presence of the definition was associated with better performance on the semantic subcategory and definition posttests but not on the phonological, orthographic, or category posttests. Findings are discussed in relation to the lexical quality hypothesis and the availability of attentional resources.

Genetic polymorphisms of glutathione S-transferases GSTM1, GSTT1, GSTP1 and GSTA1 as risk factors for schizophrenia.

Oxidative damage is thought to play a role in the predisposition to schizophrenia. We determined if the polymorphisms of the GSTP1, GSTM1, GSTT1 and GSTA1 genes, which affect the activity of these enzymes against oxidative stress, have a role as susceptibility genes for schizophrenia, analyzing 138 schizophrenic patients and 133 healthy controls. We found that the combination of the absence of GSTM1 gene with the of the GSTM1 gene with the polymorphism GSTA1*B/*B, and the presence of the GSTT1 gene, represents a risk factor for schizophrenia, indicating that the combination of different GST polymorphisms has a role in the predisposition to schizophrenia, probably affecting the capacity of the cell to detoxify the oxidized metabolites of catecholamines.

What Can Bilingual Children Tell Us About the Developmental Relationship Between Vocabulary and Grammar?

Strong correlations between vocabulary and grammar are well attested in language development in monolingual and bilingual children. What is less clear is whether there is any directionality in the relationship between the two constructs, whether it is predictive over time, and the extent to which it is affected by language input. In the present study, we analyzed data from 100 bilingual children with English as an additional language who were tested on measures of vocabulary breadth and depth, morphology, and syntax at three time points at 6-month intervals from the age of 5 and 8. We used bivariate growth models to test the directionality of the relationship between vocabulary breadth and depth, and measures of morphology and syntax; testing bilingual children allowed us to use measures of English input as covariates in the analyses. All the models showed a correlation between vocabulary and grammar, but no correlation between their growth slopes, suggesting that vocabulary and grammar grow independently. Three of the four bivariate models showed a significant correlation between the intercept of grammar skills and the slope of vocabulary growth. Length of exposure to English predicted the intercept of vocabulary breadth and grammar, suggesting that children exposed to English earlier had larger vocabularies and better morpho-syntactic skills. Current English input predicted the intercept of both measures of vocabulary as well as the slope for vocabulary depth, the only measure for which there was a significant relationship between intercept and slope, suggesting a Matthew effect for this dimension of vocabulary. All materials, data, and code are available at https://osf.io/vaq56/. Research highlights Vocabulary breadth and morphological and syntactic skills increased linearly for all participants, without any difference between lower and higher achieving children. Vocabulary depth grew more over time for those children with deeper vocabulary knowledge and higher levels of current English input at the start of the study. All of the bivariate growth models showed a correlation between vocabulary and grammar, but failed to show any correlation between their growth. Significant relationships between the intercept of grammar and the growth of vocabulary showed steeper lexical growth in children with better grammar skills. Length of exposure to English had an effect on morphological and syntactic skills, while only current English input had an effect on vocabulary depth.

Surfactant Interactions with Protein-Coated Surfaces: Comparison between Colloidal and Macroscopically Flat Surfaces.

Surface interactions with polymers or proteins are extensively studied in a range of industrial and biomedical applications to control surface modification, cleaning, or biofilm formation. In this study we compare surfactant interactions with protein-coated silica surfaces differing in the degree of curvature (macroscopically flat and colloidal nanometric spheres). The interaction with a flat surface was probed by means of surface plasmon resonance (SPR) while dynamic light scattering (DLS) was used to study the interaction with colloidal SiO2 (radius 15 nm). First, the adsorption of bovine serum albumin (BSA) with both SiO2 surfaces to create a monolayer of coating protein was studied. Subsequently, the interaction of these BSA-coated surfaces with a non-ionic surfactant (a decanol ethoxylated with an average number of eight ethoxy groups) was investigated. A fair comparison between the results obtained by these two techniques on different geometries required the correction of SPR data for bound water and DLS results for particle curvature. Thus, the treated data have excellent quantitative agreement independently of the geometry of the surface suggesting the formation of multilayers of C10PEG over the protein coating. The results also show a marked different affinity of the surfactant towards BSA when the protein is deposited on a flat surface or individually dissolved in solution.

The impact of warfarin on operative delay and 1-year mortality in elderly patients with hip fracture: a retrospective observational study.

BACKGROUND: Guidelines underline the importance of early surgery in elderly patients with proximal femoral fractures. However, most of these patients present a high number of comorbidities, some of which require the use of warfarin. Waiting for INR decrease is a cause of surgical delay, and this influences negatively their outcome. METHODS: We retrospectively reviewed all patients with proximal femoral fracture admitted to our unit from March 2013 to March 2017 to determine whether warfarin therapy is associated with reduction of survival, delay of surgery, and increased blood loss. From 1706 patient, a total of 1292 fulfilled the eligibility criteria and were included. Data regarding general information (type of fracture according to AO/OTA classification), pharmacological history regarding anticoagulant therapy pre-admission, surgery (type of surgery and time to surgery), clinical findings (blood loss), and date of exitus were collected. RESULTS: We identified 157 patients with warfarin, 442 with antiplatelet agents (aspirin, clopidogrel, ticlopidin), and 693 in the control group. We observed a significant difference in the warfarin group regarding an increased ASA score, Charlson Comorbidity Index, and blood loss. Patients taking warfarin experience delay to the theater significantly more than the other groups. Patients in warfarin therapy have a 42% higher risk of death within 1 year from their surgery. Patients who underwent surgery after 48 h have 1.5 times higher risk of mortality with respect to the patients who underwent surgery within 48 h. CONCLUSION: Warfarin therapy at the time of proximal femoral fractures is associated with increased time to surgery, blood loss, and mortality.

Below-elbow or above-elbow cast for conservative treatment of extra-articular distal radius fractures with dorsal displacement: a prospective randomized trial.

BACKGROUND: Distal radial fractures are common traumatic injuries, but their management remains controversial also in case of conservative treatment regarding the type of immobilisation. Hence, we conducted a two-arm, parallel-group, prospective randomised trial to compare the capacity of long casts (above-elbow) and short casts (below-elbow) to maintain the reduction of extra-articular distal radius fractures with dorsal displacement (AO/OTA classification: 2R3A2.2). METHODS: Seventy-four eligible patients with AO/OTA 2R3A2.2 fractures treated with closed reduction and cast immobilisation were randomised to the long cast group (n°= 37) or to the short cast group (n°= 37). Baseline radiological parameters, radial inclination (RI), radial height (RH), ulnar variance (UV) and palmar tilt (PT) were taken, and compared with clinical (DASH, Mayo Wrist and Mayo Elbow) and radiological scores taken at 7-10 days, 4 weeks and 12 weeks. Furthermore, to evaluate correlations between radiological parameters and functional outcomes, patients were divided into two groups according to whether or not their radiological parameters at Follow-ups 2 and 3 were acceptable, i.e. within the range 11-12 mm for RH, 16°-28° for RI, - 4-+ 2 mm for UV and 0°-22° for PT. RESULTS: Patient demographic and baseline radiological parameters were similar between groups. At follow-up, there were no statistically significant differences between the two types of cast in terms of RI, RH, UV or PT, or Mayo wrist or DASH scores. Short cast group patients displayed better Mayo elbow score at follow-up 2 (4 weeks), but this difference was no longer statistically significant at follow-up 3 (12 weeks). No statistically significant differences in clinical outcomes were found between patients who presented acceptable radiographic parameters at follow-up and those who did not. CONCLUSION: As there were no significant differences between short casts and long casts in terms of fracture reduction maintenance or clinical outcomes, short casts are an effective method of post-reduction immobilisation in AO/OTA 2R3A2.2 fracture of the radius. Radiological parameters outside the range conventionally considered acceptable do not preclude a satisfactory clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov PRS, NCT04062110. Registred 20 August 2019.

Fatty acidomics: Evaluation of the effects of thermal treatments on commercial mussels through an extended characterization of their free fatty acids by liquid chromatography - Fourier transform mass spectrometry.

An unprecedented characterization of free fatty acids (FFA) in the lipid extracts of fresh or thermally treated mussels of sp. Mytilus galloprovincialis, including up to 128 saturated, mono- or poly-unsaturated and 63 oxidized (i.e., modified by hydroxylic, carbonylic and/or epoxylic groups) compounds, was achieved using reverse phase chromatography coupled to electrospray ionization-Fourier transform single and tandem mass spectrometry (RPC-ESI-FTMS,MS/MS). Subsequent Principal Components Analysis (PCA) evidenced several effects of thermal treatments on the mussel FFA profiles. In particular, death-inducing low temperature treatments (freezing at -16 °C or refrigeration at 4 °C for several days) induced a peculiar increase in the incidence of FFA, whereas the effect was absent in mussels undergoing death upon prolonged storage at room temperature (25 °C, 6 h) or fast cooking (100 °C, 5 min). Alive mussels, either fresh or resulting from short term (up to 48 h) refrigeration were actually indistinguishable by PCA, although subtle seasonal effects were observed.

Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells.

It is known that melanoma develops as a consequence of multifactorial alterations. To date several studies indicate the effective implication of p16 as a tumor suppressor gene with a major role in either the development or progression of human melanoma. Deregulation of melanoma cell growth has been widely associated with mutations in the p16-cyclin D/cdk4-pRb pathway. Recently anticancer therapies are focused on restoration of p16 CDK inhibitory function and other proteins unregulated in melanoma cell cycle pathway (e.g., c-myc, p27). A combined strategy for restoration of normal homeostasis in the melanoma skin with targeted delivery of apoptosis-inducing agents does not seems to be far obtained. New class of antitumoral agents are emerging: histone deacetylase (HDAC) inhibitors have attracted much interest because of their ability to arrest cell growth, induce cell differentiation, and in some cases, induce apoptosis of cancer cells. Recently, attention has been focused on the ability of HDAC inhibitors to induce perturbation in cell cycle regulatory protein (e.g., p21(CIP1)) and down-regulation of survival signalling pathway. In the present study, we have examined the effect of valproic acid (VPA) on M14 human melanoma cell line. Here we observed that VPA induces cell cycle arrest and apoptosis sensitising melanoma cells to cis-platin and etoposide treatment. IC(50) dose (2.99 mM) of VPA was able to induce G(1) arrest (up to 75%) in association with upregulation of p16, p21 and cyclin-D1 related to Rb ipo-phosphorilation. In addition VPA activated apoptosis (50%) in M14 cells, when given alone or in combination with antitumoral agents. The ability of valproic acid to reestablished the G(1) pathway in melanoma cells suggests a potential application of VPA in melanoma therapeutic protocols.

Curcumin and cyclopalladated complexes: a recipe for bifunctional biomaterials.

The first examples of binuclear and mononuclear ortho-palladated complexes based on a functionalized 2-phenylquinoline ligand have been synthesized and fully characterized. Conjugating cyclopalladated fragments to curcumin family biologically active beta-diketones gives in one single molecule two different functionalities. The structural variations based on the curcuminoid structure have been tested for their in vitro cytotoxic activity. The activity of complexes comprised of a cyclopalladated fragment conjugated to functionalized bioactive ligands, represents the potential of organometallic systems in generating new bifunctional biomaterials.

Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation.

The mouse neuroblastoma N18TG2 clone is unable to differentiate and is defective for the enzymes of the biosynthesis of neurotransmitters. The forced expression of choline acetyltransferase (ChAT) in these cells results in the synthesis and release of acetylcholine (Ach) and hence in the expression of neurospecific features and markers. To understand how the expression of ChAT triggered neuronal differentiation, we studied the differences in genome-wide transcription profiles between the N18TG2 parental cells and its ChAT-expressing 2/4 derived clone. The engagement of the 2/4 cells in the neuronal developmental program was confirmed by the increase of the expression level of several differentiation-related genes and by the reduction of the amount of transcripts of cell cycle genes. At the same time, we observed a massive reorganization of cytoskeletal proteins in terms of gene expression, with the accumulation of the nucleoskeletal lamina component Lamin A/C in differentiating cells. The increase of the Lmna transcripts induced by ChAT expression in 2/4 cells was mimicked treating the parental N18TG2 cells with the acetylcholine receptor agonist carbachol, thus demonstrating the direct role played by this receptor in neuron nuclei maturation. Conversely, a treatment of 2/4 cells with the muscarinic receptor antagonist atropine resulted in the reduction of the amount of Lmna RNA. Finally, the hypothesis that Lmna gene product might play a crucial role in the ChAT-dependent molecular differentiation cascade was strongly supported by Lmna knockdown in 2/4 cells leading to the downregulation of genes involved in differentiation and cytoskeleton formation and to the upregulation of genes known to regulate self-renewal and stemness.

Acridine Orange based platinum(II) complexes inducing cytotoxicity and cell cycle perturbation in spite of GSTP1 up-regulation.

A series of new ionic Pt(II) complexes of general formula [Pt(II)(A)n(Cl)(AO)]X (A=en, NH3; n=1, 2; X-=BF4-, NO3-, PF6-, CF3SO3-), 1-5, containing Acridine Orange (AO) bound to the metal atom through the endocyclic N atom, have been tested in human melanoma cells (M14, JR8 and PLF2), human neuroblastoma cell line SH-SY5Y and its cis-platin resistant subline SH-SY5Yres. The Pt(II) compounds, and in particular complexes 1 and 4, exhibit higher cytotoxic activity at lower concentration compared to cis-DDP in melanoma cells, affecting cell growth behavior and causing cell cycle perturbation. Moreover, M14 and JR8 cell lines were not able to rescue the impairment due to the new Pt(II) complexes since perturbation of cell cycle phases and cell proliferation inhibition were found after 72 h of recovery time. In order to evaluate whether GSTP1 may play a role in chemo-resistance of our melanoma model, we investigated the effect of the treatment with these Pt(II) compounds on GSTP1 gene expression. Up-regulation of GSTP1, evaluated by Qreal-time PCR was observed after treatment with complexes 1 and 4, showing that the effect of these Pt(II) compounds is GSTP1 indipendent. The lack of resistance of the new Pt(II)-AO complexes and their cytotoxicity, cell growth and cell cycle recovery in melanoma cells provide the basis for the development of new platinum anticancer compounds, directed to those tumors that over express GSTs enzymes.

Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells.

Ets2 is a member of the Ets family of transcription factors that in humans comprise 25 distinct members. Various Ets-domain transcription factors have been implicated in cancer development. Ets2 is expressed in prostate and breast cancer cells and is thought to have a role in promoting growth and survival in these cell types. However, a definitive role and the mechanisms whereby Ets2 acts in cancer cells are still unclear. Structural and functional similarities as well as overlapping DNA binding specificities complicate the identification of the specific roles of the various Ets factors. In this study, we used a triplex-forming oligonucleotide (TFO) to selectively inhibit Ets2 transcription in prostate cancer cells. We had previously shown that the Ets2-targeting TFO, which was directed to a unique purine-rich sequence critical for Ets2 promoter activity, acted with a high degree of sequence-specificity and target selectivity. TFO-mediated downregulation of Ets2 in prostate cancer cells induced important phenotypic changes, including inhibition of anchorage-dependent and anchorage -independent growth, cell cycle alterations and induction of apoptotic cell death. Expression of Ets2 under the control of a heterologous promoter abolished the anti-proliferative effects of the TFO in both short- and long-term assays, suggesting that these effects were a direct result of downregulation of Ets2 transcription and confirming target selectivity of the TFO. Furthermore, normal human fibroblasts, which expressed low levels of Ets2, were not affected by the Ets2-targeting TFO. Downregulation of Ets2 in prostate cancer cells was associated with reduced levels of the anti-apoptotic protein bcl-x(L) and growth regulatory factors cyclin D1 and c-myc. These data revealed a specific role of this transcription factor in promoting growth and survival of prostate cancer cells. Furthermore, the activity and selectivity of the Ets2-targeting TFO suggest that it might represent a valid approach to prostate cancer therapy.

MyoD induces apoptosis in the absence of RB function through a p21(WAF1)-dependent re-localization of cyclin/cdk complexes to the nucleus.

During differentiation of skeletal myoblasts, MyoD promotes growth arrest through the induction of the cdk inhibitor p21 and the accumulation of hypophosphorylated RB protein. Myoblasts lacking RB function fail to accomplish full differentiation and undergo apoptosis. Here we show that exogenous MyoD induces apoptosis in several cell backgrounds sharing RB inactivation. This process is associated with increased levels of cell cycle-driving proteins and aberrant cell cycle progression. The inability of MyoD to induce apoptosis in a p21-null background, highlights a requirement of p21 in RB-regulated apoptosis during myogenesis. This pro-apoptotic function of p21 cannot be exerted by simple p21 over-expression, but requires the co-operation of MyoD. We also suggest that the essential aspect of p21 activity involved in such a process is related to its ability to induce the nuclear accumulation and aberrant activity of cyclin/cdk complexes. These results establish a novel link between MyoD, p21 and RB during myogenesis, providing new insights into the antagonism between muscle differentiation and loss of RB function.

Ribozyme-mediated inhibition of survivin expression increases spontaneous and drug-induced apoptosis and decreases the tumorigenic potential of human prostate cancer cells.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family, which has been implicated in inhibition of apoptosis and control of mitotic progression. The finding that survivin is overexpressed in most human tumors but absent in normal adult tissues has led to the proposal of survivin as a promising therapeutic target for anticancer therapies. We decided to evaluate the effects of a ribozyme-based strategy for survivin inhibition in androgen-independent human prostate cancer cells. We constructed a Moloney-based retroviral vector expressing a ribozyme targeting the 3' end of the CUA(110) triplet in survivin mRNA, encoded as a chimeric RNA within adenoviral VA1 RNA. Polyclonal cell populations obtained by infection with the retroviral vector of two androgen-independent human prostate cancer cell lines (DU145 and PC-3) were selected for the study. Ribozyme-expressing prostate cancer cells were characterized by a significant reduction of survivin expression compared to parental cells transduced with a control ribozyme; the cells became polyploid, underwent caspase-9-dependent apoptosis and showed an altered pattern of gene expression, as detected by oligonucleotide array analysis. Survivin inhibition also increased the susceptibility of prostate cancer cells to cisplatin-induced apoptosis and prevented tumor formation when cells were xenografted in athymic nude mice. These findings suggest that manipulation of the antiapoptotic survivin pathway may provide a novel approach for the treatment of androgen-independent prostate cancer.