Diethyl 4-(6-Chloroimidazo[2,1-b]thiazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate and Ethyl 4-(6-Chloroimidazo[2,1-b]thiazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Diethyl 4-(6-chloroimidazo[2,1-b]thiazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine- 3,5-dicarboxylate and ethyl 4-(6-chloroimidazo[2,1-b]thiazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained simultaneously by the Biginelli reaction using a green protocol and curtailing reaction time

Evaluation of the osmotic concentration process to obtain dried banana sticks

Orientador: Roberto Herminio MorettiDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de AlimentosResumo: O Brasil é um país com característica agrícola e o desenvolvimento dos setores agroindustriais é de grande importância sócio-econômica e que devem ser explorados a fim de evitar o desperdício de alimentos, agregar valor aos produtos agrícolas e aumentar a renda dos produtores. A transformação industrial, à experiência de regiões e países bem sucedidos, mostra que pelo menos a transformação primária das frutas deve ser pensada pelos produtores. Isto porque é um prolongamento das atividades agrícolas, que objetiva transformar produtos perecíveis em produtos estáveis. A bananicultura é uma atividade de importância econômica e social, sendo cultivada na maioria dos países tropicais. O Brasil é o terceiro maior produtor e representa cerca de 9,0% da produção mundial, com uma área de 495 mil ha, superado apenas pela Índia e pelo Equador. O presente trabalho estudou o processo de concentração osmótica em banana nanica (Musa cavendishi) através de planejamento experimental completo com 3 variáveis independentes (tempo, espessura e concentração de ácido cítrico), utilizando soluções de açúcar invertido, à pressão atmosférica e temperatura constante de 45°C. As variáveis dependentes para os 17 experimentos realizados foram: perda de peso, perda de umidade, incorporação de sólidos, variação de sólidos totais, variação de sólidos solúveis e a relação brix / acidez (ratio) que indica o equilíbrio das características sensoriais do produto. Para identificar a melhor relação foram selecionados 4 experimentos com diferentes ratio. Estas amostras de banana préconcentradas osmoticamente foram secas em estufa com circulação forçada de ar quente a 60°C até atingirem um teor de 65% de sólidos totais. Foi realizada uma análise sensorial (teste de preferência) com as 4 amostras selecionadas. Os resultados obtidos com os experimentos mostram uma perda de umidade entre 25,13 a 38,16% no processo de concentração osmótica e um produto com boas características organolépticasAbstract: Brazil is a country with agricultural characteristics and thus the development of the agro-industrial sector is of great socio-economic importance and should be explored so as to avoid food wastage and increase the value of agricultural products and producer profit. Based on the experience of highly successful regions and countries, in industrial transformation, the primary transformation of fruits should be thought of by the producers, since this is really a prolongation of the agricultural activity, with the aim of transforming perishable products into stable ones. The culture of bananas is an economically and socially important activity, bananas being cultivated in the majority of tropical countries. Brazil is the third biggest producer, behind India and Ecuador, representing 9% of world production and occupying an area of 495 thousand hectares. This work studied the osmotic concentration of banana nanica (Musa cavendishi) using a complete experimental design with 3 independent variables (time, thickness and citric acid concentration), using invert sugar solutions, atmospheric pressure and a constant temperature of 45ºC. The variable dependents for the 17 experiments carried out were: weight loss, moisture loss, solids incorporation, variation in total solids, variation in soluble solids and the brix:acidity ratio, which indicates the equilibrium of the product sensory characteristics. Four experiments with different ratios were selected in order to identify the best ratio. These osmotically pre-concentrated banana samples were dried in a forced air incubator at 60ºC to a total solids content of 65%. A sensory preference analysis was carried out with the 4 samples selected. The results obtained showed moisture losses from 25.13 to 38.16% in the osmotic concentration process and a product with good organoleptic characteristicsMestradoMestre em Tecnologia de Alimento

An Unusual Hypopharyngeal Foreign Body Causing Dyspnea After Vertebroplasty

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Esophageal Bolus Transit in Newborns with Gastroesophageal Reflux Disease Symptoms: A Multichannel Intraluminal Impedance Study.

PURPOSE: The aim of this study was to evaluate bolus transit during esophageal swallow (ES) and gastroesophageal reflux (GER) events and to investigate the relationship between the characteristics of ES and GER events in a population of term and preterm newborns with symptoms of gastroesophageal reflux disease (GERD). METHODS: The study population consisted of term and preterm newborns referred to combined multichannel intraluminal impedance (MII) and pH monitoring for GERD symptoms. The frequency and characteristics of ES and GER events were assessed by two independent investigators. Statistical significance was set at p<0.05. RESULTS: Fifty-four newborns (23 preterm) were included in the analyses. Median bolus head advancing time corrected for esophageal length (BHATc) was shorter during mealtime than during the postprandial period (median, interquartile range): 0.20 (0.15-0.29) s/cm vs. 0.47 (0.39-0.64) s/cm, p<0.001. Median bolus presence time (BPT) was prolonged during mealtime: 4.71(3.49-6.27) s vs. 2.66 (1.82-3.73) s, p<0.001. Higher BHATc (p=0.03) and prolonged BPT (p<0.001) were observed in preterm newborns during the postprandial period. A significant positive correlation between BHATc and bolus clearance time was also observed (ρ=0.33, p=0.016). CONCLUSION: The analysis of ES and GER events at the same time by MII provides useful information to better understand the physiopathology of GERD. In particular, the analysis of BHATc during the postprandial period could help clinicians identify newborns with prolonged esophageal clearance time due to impaired esophageal motility, which could allow for more accurate recommendations regarding further tests and treatment

Loss of miR-107, miR-181c and miR-29a-3p promote activation of Notch2 signaling in pediatric high-grade gliomas (pHGGs)

The mechanisms by which microRNAs control pediatric high-grade gliomas (pHGGs) have yet to be fully elucidated. Our studies of patient-derived pHGG tissues and of the pHGG cell line KNS42 revealed down-regulation in these tumors of three microRNAs, specifically miR-107, miR-181c, and miR-29a-3p. This down-regulation increases the proliferation of KNS42 cells by de-repressing expression of the Notch2 receptor (Notch2), a validated target of miR-107 and miR-181c and a putative target of miR-29a-3p. Inhibition (either pharmacologic or genetic) of Notch2 or re-expression of the implicated microRNAs (all three combined but also individually) significantly reduced KNS42 cell proliferation. These findings suggest that Notch2 pathway activation plays a critical role in pHGGs growth and reveal a direct epigenetic mechanism that controls Notch2 expression, which could potentially be targeted by novel forms of therapy for these childhood tumors characterized by high-morbidity and high-mortality

Quantitative serological evaluation as a valuable tool in the COVID-19 vaccination campaign

Objectives: After exceptional research efforts, several vaccines were developed against SARS-CoV-2 which sustains the pandemic COVID-19. The Comirnaty vaccine showed high efficacy in clinical trials and was the first to be approved for its distribution to the general population. We evaluated the immune response induced by the first vaccine dose in different sex/age groups and subjects with or without naturally present anti-SARS-CoV-2 antibodies. Methods: As part of an Italian multicenter project (Covidiagnostix), serum samples from 4,290 health-professionals were serologically tested the day of the first vaccination dose, and 21 days later, using two different instrumentations (Siemens-Healthineers and Roche). Results: In total, 97% of samples showed the presence of specific antibodies 21 days after the vaccination dose; the percentage of non-responders increased with age in both genders. Remarkably, naturally seropositive individuals showed antibody persistence up to 11 months and an exceptionally higher vaccination response compared to subjects never infected by SARS-CoV-2. Conclusions: This study highlighted the importance of the serological test i) to identify naturally SARS-CoV-2 seropositive individuals and ii) to evaluate the antibody level elicited by the first vaccination dose. Both tests, highlighted differences in the immune response, when subjects were stratified by sex and age, and between naturally seropositive and seronegative subjects.The data obtained show how serological tests could play a crucial role in the triage of the population subjected to the vaccination campaign for COVID-19. The definition of suitable instrumentation-specific thresholds is needed to correctly follow eventually acquired post-vaccination immunity in the general population

MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors

MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells. MYCN activation, often due to genetic amplification, represents the driving oncogenic event for a number of human tumors, conferring bad prognosis and predicting very poor responses even to the most aggressive therapeutic protocols. This is prototypically exemplified by neuroblastoma, where MYCN amplification occurs in about 25% of the cases. Intriguingly, MRE11 is highly expressed and predicts bad prognosis in MYCN-amplified neuroblastoma. Due to the lack of direct means to target MYCN, we explored the possibility to trigger intolerable levels of replication stress-dependent DNA damage, by inhibiting MRE11 in MYCN-amplified preclinical models. Indeed, either MRE11 knockdown or its pharmacological inhibitor mirin induce accumulation of replication stress and DNA damage biomarkers in MYCN-amplified cells. The consequent DDR recruits p53 and promotes a p53-dependent cell death, as indicated by p53 loss- and gain-of-function experiments. Encapsulation of mirin in nanoparticles allowed its use on MYCN-amplified neuroblastoma xenografts in vivo, which resulted in a sharp impairment of tumor growth, associated with DDR activation, p53 accumulation, and cell death. Therefore, we propose that MRE11 inhibition might be an effective strategy to treat MYCN-amplified and p53 wild-type neuroblastoma, and suggest that targeting replication stress with appropriate tools should be further exploited to tackle MYCN-driven tumors

Feasibility and Acceptability of a Real-Time Telerehabilitation Intervention for Children and Young Adults with Acquired Brain Injury During the COVID-19 Pandemic: An Experience Report

This study examined the feasibility and acceptability of a telerehabilitation intervention during the COVID-19 pandemic in a sample of children and young adults with Acquired Brain Injury (ABI). Thirteen patients and/or their families agreed to participate in the speech and neuropsychological telerehabilitation sessions. The treatment was synchronous, patient centered and aimed at improving specific abilities. Sessions were held twice a week over a 10-week period. Two questionnaires were completed both by parents and therapists to assess feasibility and acceptability. Neither technical issues nor clinical obstacles were found. The quality of the therapeutic relationship played a key role in the intervention. Synchronous telerehabilitation provided several advantages both for patients and therapists. Moreover, the patient centered intervention eased the burden of the caregivers at a time of high stress. The real-time telerehabilitation treatments were deemed suitable for children and young adults with ABI. Further studies are needed to support the use of telerehabilitation as an integral part of their standard care

Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents

A small library of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones has been synthesized and screened according to protocols available at the National Cancer Institute (NCI). Some derivatives were potent antiproliferative agents, showing GI50 values in the nanomolar range. Remarkably, when most active compounds against leukemia cells were tested in human peripheral blood lymphocytes from healthy donors, were 100–200 times less cytotoxic. Some compounds, selected by the Biological Evaluation Committee of NCI, were examined to determine tubulin assembly inhibition. Furthermore, flow cytometric studies performed on HeLa, HT-29, and A549 cells, showed that compounds 14 and 25 caused a block in the G2/M phase. Interestingly, these derivatives induced apoptosis through the mitochondrial death pathway, causing in parallel significant activation of both caspase-3 and -9, PARP cleavage and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1. Finally, compound 25 was also tested in vivo in the murine BL6-B16 melanoma and E0771 breast cancer cells, causing in both cases a significant reduction in tumor volume

SAT-092 THE DUEL OF DAVID AND GOLIATH: HOW SHOULD MGFR BEAT THE ESTIMATED GFR?

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