Mageleie til ikke-intuberte intensivpasienter. En litteraturstudie med systematisk tilnærming

Bakgrunn: COVID-19 er et luftveisvirus som kan føre til ARDS med behov for ventilasjonsstøtte. Mageleie brukes som et behandlingsalternativ til pasienter med ARDS og er påvist å ha god effekt til intuberte pasienter. Etter at COVID-19 pandemien oppstod i 2020 har behovet for forskning på ikke-intuberte ARDS-pasienter behandlet med HFNO og NIV økt. Intensivsykepleiere har en sentral rolle ved å observere og tilrettelegge for at pasienter skal oppnå effekt av mageleie. Hensikt: Hensikten med denne oppgaven var å se på hvilken effekt mageleie har på ikke-intuberte intensivpasienter. Metode: Vi gjennomførte en litteraturstudie med systematisk tilnærming. Det er gjort systematiske søk etter egnet litteratur for å svare problemstillingen. Totalt ble elleve studier inkludert, hvorav en var randomisert kontrollert studie og ti kvasi-eksperimentelle studier. Resultat: Mageleie til ikke-intuberte intensivpasienter behandlet med NIV eller HFNO viser å ha positiv effekt på PaO2/FiO2 ratio og redusert behov for intubasjon. Det er ikke oppgitt komplikasjoner eller uønskede hendelser knyttet til mageleie hos ikke-intubert pasienter. Toleranse og pasientkomfort er rapportert som viktige faktorer for gjennomføring av mageleie. Konklusjon: Bruk av mageleie til pasienter behandlet med NIV og HNFO synes å være trygt og gjennomførbart. Mageleie kan forbedre oksygenering og behov for intubasjon, men intervensjonstid og toleranse knyttet til mageleie er avgjørende faktorer for gjennomføring og effekt av intervensjonen. Intensivsykepleiere har en nøkkelrolle for å trygge pasienter og tilrettelegge for økt pasientkomfort

Possible strategies for use of artificial intelligence in screen-reading of mammograms, based on retrospective data from 122,969 screening examinations

Objectives Artificial intelligence (AI) has shown promising results when used on retrospective data from mammographic screening. However, few studies have explored the possible consequences of different strategies for combining AI and radiologists in screen-reading. Methods A total of 122,969 digital screening examinations performed between 2009 and 2018 in BreastScreen Norway were retrospectively processed by an AI system, which scored the examinations from 1 to 10; 1 indicated low suspicion of malignancy and 10 high suspicion. Results were merged with information about screening outcome and used to explore consensus, recall, and cancer detection for 11 different scenarios of combining AI and radiologists. Results Recall was 3.2%, screen-detected cancer 0.61% and interval cancer 0.17% after independent double reading and served as reference values. In a scenario where examinations with AI scores 1–5 were considered negative and 6–10 resulted in standard independent double reading, the estimated recall was 2.6% and screen-detected cancer 0.60%. When scores 1–9 were considered negative and score 10 double read, recall was 1.2% and screen-detected cancer 0.53%. In these two scenarios, potential rates of screen-detected cancer could be up to 0.63% and 0.56%, if the interval cancers selected for consensus were detected at screening. In the former scenario, screen-reading volume would be reduced by 50%, while the latter would reduce the volume by 90%. Conclusion Several theoretical scenarios with AI and radiologists have the potential to reduce the volume in screen-reading without affecting cancer detection substantially. Possible influence on recall and interval cancers must be evaluated in prospective studies. Key Points Different scenarios using artificial intelligence in combination with radiologists could reduce the screen-reading volume by 50% and result in a rate of screen-detected cancer ranging from 0.59% to 0.60%, compared to 0.61% after standard independent double reading The use of artificial intelligence in combination with radiologists has the potential to identify negative screening examinations with high precision in mammographic screening and to reduce the rate of interval cancer</li

Modelo experimental em ratos no reparo ósseo do fêmur utilizando células mononucleares no plasma rico em plaquetas

As células mononucleares da medula óssea têm sido utilizadas em diversas afecções na tentativa de regeneração tecidual. (O objetivo deste estudo foi o de avaliar a adesão das células mononucleares sobre defeito crítico, com a adição do plasma rico em plaquetas (PRP) e / ou TGF-β1 (Fator de crescimento transformador Beta 1), e, por fim, verificar o reparo ósseo dos sítios defeituosos dos fêmures dos ratos. Foi criado um defeito bilateral critico nos fêmures de 33 Wistar-Kyoto ratos. Células mononucleares de medula óssea, TGF-β e PRP foram adicionadas no lado tratado da lesão e soro fisiológico no lado contralateral. Determinou-se a adesão de células mononucleares sobre o defeito crítico e reparo ósseo. A presença e consequente adesão das células mononucleares administradas nos animais tratados não foi evidenciada através da técnica de PCR. As análises radiológicas evidenciam fechamento da lesão, porém, nós não podemos afirmar que foi pelos tratamentos administrados ou pela própria regeneração óssea, quando analisadas em seis e 10 semanas pós-operatórias, haja visto não apresentarem diferenças significantes entre os grupos. Conclusões: a) As células mononucleares não aderiram ao defeito crítico criado no fêmur do rato; b) Não foi possível avaliar a eficiência dos tratamentos propostos para o reparo ósseo, por não apresentarem diferenças significativas entre os grupos.Mononuclear cells from bone marrow have been used in various treatments of diseases in an attempt to regenerate tissues. The objective of this study was to evaluate the accession and proliferation of mononuclear cells in a critical defect, with the addition of platelet-rich plasma (PRP) and / or TGF-β1 (transforming growth factor beta 1), and then to evaluate bone repair at defective sites on the femurs of rats. We created a critical defect on the bilateral femurs of 33 Wistar-Kyoto rats. Mononuclear bone marrow cells, TGF-β and PRP were added to the lesion on the treated side and saline on the contralateral side. We determined the adhesion of mononuclear cells at the critical defect and bone repair. The presence and consequent adhesion of the mononuclear cells administered to the treated animals was not demonstrated by PCR. Radiographic analysis showed closure of the lesion, but we could not affirm that this resulted from the treatments administered or by normal bone regeneration itself, when the lesion was evaluated at 6 and 10 weeks postoperative, seeing that there were no significant differences between the groups. Conclusions: a)Bone marrow mononuclear cells did not adhere at the critical defect created in the rat femur; b) It was not possible to determine the efficiency of the bone repair treatments studied, as the results did not show significant differences between the groups

Degradação do Agrotóxico Connect® com Fotocatalisador Hidroxiapatita

A utilização da hidroxiapatita como fotocatalisador é uma tecnologia promissora, pois é um material não tóxico e de fácil obtenção e suas características estruturais e físico-químicas podem ser alteradas dependendo da metodologia de síntese e dos dopantes incorporados em sua estrutura. Este trabalho estudou a eficiência da hidroxiapatita como catalisador heterogêneo na degradação do agrotóxico Connect®, utilizando-se radiação UV e radiação solar. A hidroxiapatita foi sintetizada por precipitação homogênea e dopada com metais de transição. A eficiência fotocatalítica foi dependente da hidroxiapatita utilizada, devido às alterações em sua cristalinidade, na área superficial, no tamanho dos poros, na capacidade de adsorção e na estabilidade. A hidroxiapatita apresentou eficiência de 100 % na fotodegradação do agrotóxico Connect®, (dopantes W e V), com radiação UV, em uma hora de irradiação. Utilizando-se radiação solar, foram necessárias 20 h de exposição (dopantes Zn ou Cr) para total degradação do agrotóxico, indicando a influencia do método de preparação. A degradação total do agrotóxico com radiação UV e com radiação solar ocorreu em diferentes tempos de exposição permitindo a diminuição de seus efeitos poluidores no ambiente

Getting Across the Plasma Membrane and Beyond: Intracellular Uses of Colloidal Semiconductor Nanocrystals

Semiconductor nanocrystals (NCs) are increasingly being used as photoluminescen markers in biological imaging. Their brightness, large Stokes shift, and high photostability compared to organic fluorophores permit the exploration of biological phenomena at the single-molecule scale with superior temporal resolution and spatial precision. NCs have predominantly been used as extracellular markers for tagging and tracking membrane proteins. Successful internalization and intracellular labelling with NCs have been demonstrated for both fixed immunolabelled and live cells. However, the precise localization and subcellular compartment labelled are less clear. Generally, live cell studies are limited by the requirement of fairly invasive protocols for loading NCs and the relatively large size of NCs compared to the cellular machinery, along with the subsequent sequestration of NCs in endosomal/lysosomal compartments. For long-period observation the potential cytotoxicity of cytoplasmically loaded NCs must be evaluated. This review focuses on the challenges of intracellular uses of NCs

A highly selective purine-based inhibitor of CSF1R potently inhibits osteoclast differentiation

The colony-stimulating factor 1 receptor (CSF1R) plays an important role in the regulation of many inflammatory processes, and overexpression of the kinase is implicated in several disease states. Identifying selective, smallmolecule inhibitors of CSF1R may be a crucial step toward treating these disorders. Through modelling, synthesis, and a systematic structure-activity relationship study, we have identified a number of potent and highly selective purine-based inhibitors of CSF1R. The optimized 6,8-disubstituted antagonist, compound 9, has enzymatic IC50 of 0.2 nM, and displays a strong affinity toward the autoinhibited form of CSF1R, contrasting that of other previously reported inhibitors. As a result of its binding mode, the inhibitor shows excellent selectivity (Selectivity score: 0.06), evidenced by profiling towards a panel of 468 kinases. In cell-based assays, this inhibitor shows dose-dependent blockade of CSF1-mediated downstream signalling in murine bone marrow-derived macrophages (IC50 = 106 nM) as well as disruption of osteoclast differentiation at nanomolar levels. In vivo experiments, however, indicate that improve metabolic stability is needed in order to further progress this compound class

Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>It has recently been shown that <it>NDRG2 </it>mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high <it>NDRG2 </it>expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine <it>NDRG2 </it>mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages <it>NDRG2 </it>down-regulation occurs during colonic carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>NDRG2 </it>in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). <it>NDRG2 </it>levels were normalised to <it>β-actin</it>.</p> <p>Results</p> <p><it>NDRG2 </it>mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, <it>NDRG2 </it>expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for <it>NDRG2 </it>levels to decrease with increasing Dukes' stage (p < 0.05).</p> <p>Conclusion</p> <p>Our results demonstrate that expression of <it>NDRG2 </it>is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether <it>NDRG2 </it>down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma.</p

Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study

BACKGROUND: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively. METHODS: We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes (XRCC1 Arg(194)Trp, Arg(280)His, Arg(399)Gln, XRCC3 Thr(241)Met and XPD Lys(751)Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption. RESULTS: The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46). The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96). Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89), while no association was found with risk of carcinomas. CONCLUSION: Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg(280)His polymorphism and a reduced risk associated with the XRCC1 Arg(399)Gln polymorphism. Interestingly, individuals with the XPD Lys(751)Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas

Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

<p>Abstract</p> <p>Background</p> <p>The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population.</p> <p>Methods</p> <p>We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (<it>GSTM1</it>, <it>GSTT1</it>, <it>GSTP1 </it>Ile¹⁰⁵Val, <it>EPHX1 </it>Tyr¹¹³His and <it>EPHX1 </it>His¹³⁹Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression.</p> <p>Results</p> <p>A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2^ndquartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the <it>EPHX1 </it>codon 113 polymorphism. An association was also observed for the <it>EPHX1 </it>codon 113 polymorphism in the low-risk adenomas, although not as obvious.</p> <p>Conclusion</p> <p>Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma.</p