En ce 21
e
siècle, le cancer est une maladie qui suscite particulièrement l’attention en raison de sa complexité ainsi que des impacts physiques, émotionnels et financiers sur notre vie. L’attention ...portée à la recherche et les investissements dans le traitement contre le cancer en font la maladie la plus étudiée dans les essais cliniques à l’échelle mondiale. Les infirmières de recherche clinique font partie de l’équipe de recherche en oncologie et sont un élément fondamental de réussite des essais. Leurs relations directes avec les participants d’une étude de recherche sont essentielles pour les activités des essais cliniques en première ligne. De façon générale, l’afflux et la complexité des essais cliniques en oncologie ont transformé la pratique infirmière en oncologie et ont mené à la création de la sous-spécialité unique qu’est l’infirmière de recherche clinique en oncologie. La présente revue exploratoire s’est penchée sur le rôle et la pratique futurs de l’infirmière de recherche clinique.
An ideal material for C2H6/C2H4 separation would simultaneously have the highest C2H6 uptake capacity and the highest C2H6/C2H4 selectivity. But such material is elusive. A benchmark material for ...ethane-selective C2H6/C2H4 separation is peroxo-functionalized MOF-74-Fe that exhibits the best known separation performance due to its high C2H6/C2H4 selectivity (4.4), although its C2H6 uptake capacity is moderate (74.3 cm3/g). Here, we report a family of pore-space-partitioned crystalline porous materials (CPMs) with exceptional C2H6 uptake capacity and C2H6/C2H4 separation potential (i.e., C2H4 recovered from the mixture) despite their moderate C2H6/C2H4 selectivity (up to 1.75). The ethane uptake capacity as high as 166.8 cm3/g at 1 atm and 298 K, more than twice that of peroxo-MOF-74-Fe, has been achieved even though the isosteric heat of adsorption (21.9–30.4 kJ/mol) for these CPMs is as low as about one-third of that for peroxo-MOF-74-Fe (66.8 kJ/mol). While the overall C2H6/C2H4 separation potentials have not yet surpassed peroxo-MOF-74-Fe, these robust CPMs exhibit outstanding properties including high thermal stability (up to 450 °C) and aqueous stability, low regeneration energy, and a high degree of chemical and geometrical tunability within the same isoreticular framework.
A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a ...traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis - findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.).
International hospitals and healthcare facilities are facing catastrophic financial challenges related to the COVID-19 pandemic. The American Hospital Association estimates a financial impact of ...$202.6 billion in lost revenue for America's hospitals and healthcare systems, or an average of $50.7 billion per month. Furthermore, it could cost low- and middle-income countries ~ US$52 billion (equivalent to US$8.60 per person) each four weeks to provide an effective healthcare response to COVID-19. In the setting of the largest daily COVID-19 new cases in the US, this burden will influence patient care, surgeries, and surgical outcomes. From a global economic standpoint, The World Bank projects that global growth is projected to shrink by almost 8% with poorer countries feeling most of the impact, and the United Nations projects that it will cost the global economy around 2 trillion dollars this year. Overall, a lack of preparedness was a major contributor to the struggles experienced by healthcare facilities around the world. Items such as personal protective equipment (PPE) for healthcare workers, hospital equipment, sanitizing supplies, toilet paper, and water were in short supply. These deficiencies were exposed by COVID-19 and have prompted healthcare organizations around the world to invent new essential plans for pandemic preparedness. In this paper, we will discuss the economic impact of COVID-19 on US and international hospitals, healthcare facilities, surgery, and surgical outcomes. In the future, the US and countries around the world will benefit from preparing a plan of action to use as a guide in the event of a disaster or pandemic.
Adult hippocampal neurogenesis has been linked to learning but details of the relationship between neuronal production and memory formation remain unknown. Using low dose irradiation to inhibit adult ...hippocampal neurogenesis we show that new neurons aged 4–28 days old at the time of training are required for long-term memory in a spatial version of the water maze. This effect of irradiation was specific since long-term memory for a visibly cued platform remained intact. Furthermore, irradiation just before or after water maze training had no effect on learning or long-term memory. Relationships between learning and new neuron survival, as well as proliferation, were investigated but found non-significant. These results suggest a new role for adult neurogenesis in the formation and/or consolidation of long-term, hippocampus-dependent, spatial memories.
Leptonic CP violation search, neutrino mass hierarchy determination, and the precision measurements of oscillation parameters for a unitary test of the leptonic mixing matrix are among the major ...targets of the ongoing and future neutrino oscillation experiments. The work explores the physics reach for these targets by around 2027, when the third generation of the neutrino experiments starts operation, with a combined sensitivity of three experiments: T2K-II, NO νA extension, and JUNO. It is shown that a joint analysis of these three experiments can conclusively determine the neutrino mass hierarchy. Also, at certain values of true δCP, it provides closely around a 5σ confidence level (C.L.) to exclude C P -conserving values and more than a 50% fractional region of true δCP values can be explored with a statistic significance of at least a 3σ C.L. Besides, the joint analysis can provide unprecedented precision measurements of the atmospheric neutrino oscillation parameters and a great offer to solve the θ23 octant degeneracy in the case of nonmaximal mixing.
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► The efficiency of Kerria japonica and Rosa chinensis dye is 0.22%, 0.29% respectively. ► In the presence of sugar molecule, it was increased to 0.29% for K. japonica and decreased ...to 0.27% for R. chinensis. ► Implementation of natural dye in DSSC is cost effective compared to the metal based dyes.
The natural dyes carotenoid and anthocyanin were extracted from Kerria japonica and Rosa chinensis, respectively, using a simple extraction technique without any further purification. They were then used as sensitizers in dye-sensitized solar cells (DSSCs), and their characteristics were studied. The ranges of short-circuit current (JSC) from 0.559 to 0.801(mA/cm2), open-circuit voltage (VOC) from 0.537 to 0.584V, and fill factor from 0.676 to 0.705 were obtained for the DSSCs made using the extracted dyes. Sugar molecules were added externally to the dye for stabilization and to increase the conversion efficiency. The efficiencies of the K. japonica and R. chinensis dyes were 0.22% and 0.29%, respectively; after the addition of sugar, the efficiency increased to 0.29% for K. japonica and decreased to 0.27% for R. chinensis. Thus, the addition of sugar molecules increased the conversion efficiency slightly with the carotenoid dye of K. japonica, while there was no considerable change with the anthocyanin of R. chinensis. This paper briefly discusses the simple extraction technique of these natural dyes and their performance in DSSCs.
Background
Small bowel obstruction due to adhesions (aSBO) is a common indication for admission to a surgical unit. Despite the prevalence of this condition, the short‐ and medium‐term survival of ...this patient population has not been well described. The purpose of this study was to measure the short‐ and medium‐term survival of patients admitted to hospital with aSBO.
Methods
Linked administrative data were used to identify patients admitted to hospital in Ontario, Canada, for aSBO between 2005 and 2011. Patients were divided into two groups: those aged less than 65 years (younger group) and those aged 65 years and older (older group). Thirty‐day, 90‐day and 1‐year mortality rates were estimated. One‐year mortality was compared with that in the general population, adjusting for age and sex. The timing of deaths in relation to admission was assessed, as well as the proportion of patients discharged before experiencing short‐term mortality.
Results
There were 22 197 patients admitted to hospital for aSBO for the first time in the study interval. Mean age was 64·5 years and 52·2 per cent of the patients were women. Overall, the 30‐day, 90‐day and 1‐year mortality rates for the cohort were 5·7 (95 per cent c.i. 5·4 to 6·0), 8·7 (8·3 to 9·0) and 13·9 (13·4 to 14·3) per cent respectively. For both groups, the 1‐year risk of death was significantly greater than that of the age‐matched general population. The majority of deaths (62·5 per cent) occurred within 90 days of admission, with 36·4 per cent occurring after discharge from the aSBO admission.
Conclusion
Patients admitted with aSBO have a high short‐term mortality rate. Increased monitoring of patients in the early period after admission is advisable.
Antecedentes
La obstrucción del intestino delgado por adherencias (adhesive small bowel obstruction, aSBO) es una indicación frecuente de ingreso en una unidad quirúrgica. A pesar de la prevalencia de esta patología, la supervivencia de estos pacientes a corto y a medio plazo no ha sido bien descrita. El objetivo de este estudio fue determinar la supervivencia a corto y a medio plazo de pacientes con aSBO ingresados en el hospital.
Métodos
Utilizando el enlace de datos administrativos se identificaron a los pacientes ingresados por aSBO en Ontario, Canadá, entre 2005‐2011. Los pacientes se dividieron en dos subgrupos: los menores de 65 años de edad (subgrupo joven) y los de 65 años o más (subgrupo mayor). Se estimó la mortalidad a los 30 días, 90 días y a 1 año. La mortalidad a 1 año se comparó con la de la población general, ajustando por edad y sexo. Se evaluó el momento del fallecimiento respecto al ingreso, así como la proporción de pacientes que fueron dados de alta antes de fallecer a los 30 días.
Resultados
Durante el periodo de estudio se ingresaron en el hospital 22.197 pacientes con aSBO por primera vez. La edad media de los pacientes era de 65 años y un 52% eran mujeres. La mortalidad global de la cohorte a los 30 días, a los 90 días y a 1 año fue del 5,7% (i.c. del 95%: 5,4‐6,0%), 8,3% (i.c. del 95%: 8,3‐9,0%) y 13% (i.c. del 95%: 12,9‐15,0%), respectivamente. Para ambos subgrupos, el riesgo de mortalidad a 1 año fue significativamente mayor que en la población general emparejada por edad. La mayoría de los fallecimientos (59%) ocurrieron durante los 90 días del ingreso, con un 36% tras el alta después del ingreso por aSBO.
Conclusión
Los pacientes ingresados por aSBO presentan una alta mortalidad a corto plazo. Se recomienda incrementar la vigilancia de estos pacientes en el periodo temprano tras el alta hospitalaria.
The risk of 30‐day, 90‐day and 1‐year mortality is extremely high among patients admitted for adhesive small bowel obstruction. Moreover, more than one‐third of deaths occur after discharge from hospital but within 90 days of the initial small bowel obstruction admission, suggesting that more careful monitoring of patients in this early period after admission may be critical.
Higher than expected.
Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell ...survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
Key points
LRRC8A‐containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor‐α (TNFα) signalling. Here we show that LRRC8C and 8D ...also co‐immunoprecipitate with Nox1 in vascular smooth muscle cells.
LRRC8C knockdown inhibited TNFα‐induced O2•− production, receptor endocytosis, nuclear factor‐κB (NF‐κB) activation and proliferation while LRRC8D knockdown enhanced NF‐κB activation. Significant changes in LRRC8 isoform expression in human atherosclerosis and psoriasis suggest compensation for increased inflammation.
The oxidant chloramine‐T (ChlorT, 1 mM) weakly (∼25%) inhibited LRRC8C currents but potently (∼80%) inhibited LRRC8D currents. Substitution of the extracellular loop (EL1, EL2) domains of 8D into 8C conferred significantly stronger (69%) ChlorT‐dependent inhibition.
ChlorT exposure impaired subsequent current block by DCPIB, which occurs through interaction with EL1, further implicating external oxidation sites.
LRRC8A/C channels most effectively sustain Nox1 activity at the plasma membrane. This may result from their ability to remain active in an oxidized microenvironment.
Tumour necrosis factor‐α (TNFα) activates NADPH oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs), producing superoxide (O2•–) required for subsequent signalling. LRRC8 family proteins A–E comprise volume‐regulated anion channels (VRACs). The required subunit LRRC8A physically associates with Nox1, and VRAC activity is required for Nox activity and the inflammatory response to TNFα. VRAC currents are modulated by oxidants, suggesting that channel oxidant sensitivity and proximity to Nox1 may play a physiologically relevant role. In VSMCs, LRRC8C knockdown (siRNA) recapitulated the effects of siLRRC8A, inhibiting TNFα‐induced extracellular and endosomal O2•− production, receptor endocytosis, nuclear factor‐κB (NF‐κB) activation and proliferation. In contrast, siLRRC8D potentiated NF‐κB activation. Nox1 co‐immunoprecipitated with 8C and 8D, and colocalized with 8D at the plasma membrane and in vesicles. We compared VRAC currents mediated by homomeric and heteromeric LRRC8C and LRRC8D channels expressed in HEK293 cells. The oxidant chloramine T (ChlorT, 1 mM) weakly inhibited 8C, but potently inhibited 8D currents. ChlorT exposure also impaired subsequent current block by the VRAC blocker DCPIB, implicating external sites of oxidation. Substitution of the 8D extracellular loop domains (EL1, EL2) into 8C conferred significantly stronger ChlorT‐mediated inhibition of 8C currents. Our results suggest that LRRC8A/C channel activity can be effectively maintained in the oxidized microenvironment expected to result from Nox1 activation at the plasma membrane. Increased ratios of 8D:8C expression may potentially depress inflammatory responses to TNFα. LRRC8A/C channel downregulation represents a novel strategy to reduce TNFα‐induced inflammation.
Key points
LRRC8A‐containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor‐α (TNFα) signalling. Here we show that LRRC8C and 8D also co‐immunoprecipitate with Nox1 in vascular smooth muscle cells.
LRRC8C knockdown inhibited TNFα‐induced O2•− production, receptor endocytosis, nuclear factor‐κB (NF‐κB) activation and proliferation while LRRC8D knockdown enhanced NF‐κB activation. Significant changes in LRRC8 isoform expression in human atherosclerosis and psoriasis suggest compensation for increased inflammation.
The oxidant chloramine‐T (ChlorT, 1 mM) weakly (∼25%) inhibited LRRC8C currents but potently (∼80%) inhibited LRRC8D currents. Substitution of the extracellular loop (EL1, EL2) domains of 8D into 8C conferred significantly stronger (69%) ChlorT‐dependent inhibition.
ChlorT exposure impaired subsequent current block by DCPIB, which occurs through interaction with EL1, further implicating external oxidation sites.
LRRC8A/C channels most effectively sustain Nox1 activity at the plasma membrane. This may result from their ability to remain active in an oxidized microenvironment.
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