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Liver cancer is one of the most common cancers, accounting for the sixth-highest number of new cases and the third-highest number of deaths. Sorafenib is a well-known targeted therapy for the treatment of liver cancer. Sorafenib's therapeutic use has also been linked to side effects such as diarrhea, hypertension, and skin toxicity. As a result, combining Sorafenib with other therapeutic agents is required to avoid unwanted side effects. In this study, we tried to test the combination effect of Sorafenib and Curcuma aromatica extract. The cytotoxic, migration, and colony assays were used to investigate the conjugated effect of C. aromatica extract and Sorafenib on liver cancer cell growth inhibition. At the same Sorafenib concentration, the more C. aromatica extract supplemented, the higher the cell death rate, with a statistically significant difference. To assess the relative potency of the combination, an isobologram model integrated into the CalcuSyn software was used. All of the data points were located in a synergistic area below the additive line, according to the schematic isobologram and CI distribution chart. The results indicated that the effect of sorafenib and C. aromatica was synergistic. C. aromatica extract could be used to help treat liver cancer when used with sorafenib.

This article investigates how the climate imaginaries of Gitga’at people (an Indigenous Nation on the northwest coast of what is now known as British Columbia, Canada) take shape on the lands and waters of their territory and whether these imaginaries differ from or actively resist hegemonic settler-colonial imaginaries of climate futures. We analyze community values-led climate adaptation planning documents and actions, and knowledge-holder interviews to answer our research questions. Our interpretation as collaborative non-Indigenous scholars is that lived experiences and millennia-old relationship between Gitga’at people and their ancestral territory play a strong role in informing a contemporary climate imaginary of “turning to the territory”. This imaginary is evidenced in the ways the Gitga’at Nation is currently adapting to impacts of climate change in their territory. We juxtapose “turning to the territory” with common settler climate imaginaries and find that it moves beyond the paralyzing “climate apocalypse” imaginary, and in fact encompasses “techno-markets” and “sustainable lifestyles” themes within a frame of Indigenous self-determination and resurgence. However, it is at odds with the hegemonic “fossil fuels forever” imaginary enacted by settler-colonial governments.

This study aims to compare the effect of fTCP-contained toothpaste in combination with 950 ppm fluoride on primary dentin caries surface to ordinary 1100 ppm fluoride toothpaste by using estimation statistics. Dental caries with deep lesion and dentin exposure from nine primary teeth were cut into two equal parts and randomly divided into two groups in a before-after study. Each group was brushed with one type of toothpaste two times per day for 28 days and rested in artificial saliva. SEM images of cavity bottom surfaces and energy-dispersive X-ray spectrometry (EDX) were used to determine the percentage of calcium (Ca), phosphorus (P), fluoride (F) and oxygen (O) at six continuous measured areas from the surface of the cavity bottom into 45 µm depth before and after brushing. About 95% confidence interval of the mean difference was calculated by performing bootstrap resampling with 5000 resamples followed by comparison analysis. The percentage of Ca, P, F, O was shifted after treatment. There was no difference between the two groups. The SEM images reflected a similar illustration of EDX data. The combination of fTCP and 950 ppm fluoride in toothpaste showed equivalent effectiveness to the 1100 ppm fluoride toothpaste in primary dentin caries.

The aim of this study was to investigate genetic structures and expression ofblaOXA-58gene in fiveAcinetobacter baumanniiclinical isolates recovered from two hospitals in southern Vietnam during 2012-2014.A. baumanniiisolates were identified by automated microbiology systems and confirmed by PCR. All isolates were characterized as multidrug resistant by antimicrobial testing using the disk diffusion method. Four imipenem susceptible and one nonsusceptible isolates (MIC>32 μg·ml-1) were identified by E-test. PCR amplification ofblaOXA-58gene upstream and downstream sequences revealed the presence of ISAba3at both locations in one multidrug-resistant isolate. Semiquantitation ofblaOXA-51andblaOXA-58gene expression was performed by the 2-ΔΔCtmethod. TheblaOXA-51gene expression of five isolates showed little difference, but the isolate bearing ISAba3-blaOXA-58-ISAba3exhibited significantly higherblaOXA-58mRNA level. Higherβ-lactamases activity in periplasmic than cytoplasmic fraction was found in most isolates. The isolate overexpressingblaOXA-58gene possessed very high periplasmic enzyme activity. In conclusion, theA. baumanniiisolate bearing ISAba3-blaOXA-58gene exhibited high resistance to imipenem, corresponding to an overexpression ofblaOXA-58gene and very high periplasmicβ-lactamase activity.

Funding: This research was supported by a Mitacs Accelerate Internship (IT21479); the Save Our Seas Foundation; Willow Grove Foundation; Donner Canadian Foundation; Tides Canada; LUSH Charity Pot; private donations to North Coast Cetacean Society; Fisheries and Oceans Canada; and the Canada Nature Fund for Aquatic Species at Risk (CANAFSAR 2019-2021). Fin whales (Balaenoptera physalus) are widely considered an offshore and oceanic species, but certain populations also use coastal areas and semi-enclosed seas. Based upon fifteen years of study, we report that Canadian Pacific fin whales (B. p. velifera) have returned to the Kitimat Fjord System (KFS) in the Great Bear Rainforest, and have established a seasonally resident population in its intracoastal waters. This is the only fjord system along this coast or elsewhere in which fin whales are known to occur regularly with strong site fidelity. The KFS was also the only Canadian Pacific fjord system in which fin whales were commonly found and killed during commercial whaling, pointing to its long-term importance. Traditional knowledge, whaling records, and citizen science databases suggest that fin whales were extirpated from this area prior to their return in 2005-2006. Visual surveys and mark-recapture analysis documented their repopulation of the area, with 100-120 whales using the fjord system in recent years, as well as the establishment of a seasonally resident population with annual return rates higher than 70%. Line transect surveys identified the central and outer channels of the KFS as the primary fin whale habitat, with the greatest densities occurring in Squally Channel and Caamano Sound. Fin whales were observed in the KFS in most months of the year. Vessel- and shore-based surveys (27,311 km and 6,572 hours of effort, respectively) indicated regular fin whale presence (2,542 detections), including mother-calf pairs, from June to October and peak abundance in late August-early September. Seasonal patterns were variable year-to-year, and several lines of evidence indicated that fin whales arrived and departed from the KFS repeatedly throughout the summer and fall. Additionally, we report on the population's social network and morphometrics. These findings offer insights into the dynamics of population recovery in an area where several marine shipping projects are proposed. The fin whales of the Great Bear Rainforest represent a rare exception to general patterns in this species' natural history, and we highlight the importance of their conservation. Publisher PDF

Skeletal muscle dysfunction is an important systemic consequence of chronic obstructive pulmonary disease (COPD) that worsens the natural cause of the disease. Up to a third of all people with COPD ...

Skeletal muscle dysfunction is an important systemic consequence of chronic obstructive pulmonary disease (COPD) that worsens the natural cause of the disease. Up to a third of all people with COPD express some form of impairment which encompasses reductions in strength and endurance, as well as an increased fatigability. Considering this complexity, no single test could be used to measure and monitor all aspects of the impaired skeletal muscle function within the COPD population, resulting in a wide range of available tests and measurement techniques. The aim of the current review is to highlight current and new perspectives relevant to skeletal muscle function measurements within the COPD population in order to provide guidance for researchers as well as for clinicians. First of all, standardized and clinically feasible measurement protocols, as well as normative values and predictive equations across the spectrum of impaired function in COPD, are needed before assessment of skeletal muscle function can become a reality in clinical praxis. This should minimally target the quadriceps muscle; however, depending on the objective of measurements, eg, to determine upper limb muscle function or walking capacity, other muscles could also be tested. Furthermore, even though muscle strength measurements are important, current evidence suggests that other aspects, such as the endurance and power capacity of the muscle, should also be considered. Moreover, although static (isometric) measurements have been favored, dynamic measurements of skeletal muscle function should not be neglected as they, in a larger extent than static measurements, are related to tasks of daily living. Lastly, the often modest relationships between functional tests and skeletal muscle function measurements indicate that they evaluate different constructs and thus cannot replace one another. Therefore, for accurate measurements of skeletal muscle function in people with COPD, specific and formal measurements should still be prioritized.

Researchers and government agencies are increasingly embracing Indigenous knowledge to inform ecological monitoring. However, there are few detailed accounts of designing monitoring methods based in Indigenous knowledge to meet Indigenous objectives. This research details the design of a program initiated by the Gitga’at First Nation to document the knowledge and observations of their harvesters as a contemporary monitoring initiative. We, Gitga’at and academic researchers, first conducted informal interviews with knowledge holders to gauge interest and to establish community objectives. We then convened community meetings and workshops to design methods to document harvesters’ knowledge and observations. We tested and revised these methods (a post-harvest season interview guide, and a logbook to be completed by harvesters) over the course of two harvest seasons. Semi-structured interviews were more successful than the logbooks in meeting multiple community monitoring objectives. However, we were encouraged by younger participants’ suggestions to develop a digital app based on the logbook to encourage future participation. Our work can serve as a guide to other Indigenous peoples and collaborators who wish to leverage the knowledge of their land and (or) sea users, and the methods we develop are available to adapt to other cultural, social-ecological, and political contexts.

"Chronic obstructive pulmonary disease (COPD) is often accompanied by extrapulmonary manifestations such as limb muscle dysfunction. This term encompasses several features, including atrophy, weakness, and reduced oxidative capacity. Clinicians should become accustomed with this manifestation of COPD because of its relevance for important outcomes such as exercise tolerance and survival. Measuring muscle strength and mass can be performed with simple and valid tools that could be implemented in clinical practice. One identified, limb muscle dysfunction is amenable to therapy such as exercise training that has been repeatedly shown to improve muscle mass, strength, and oxidative capacity in COPD."

We will study the effects of the methanol extract of Sphagneticola trilobata (L.) Pruski (Asteraceae) (MeST) on the growth of leukemia cells that may contain the BCR/ABL gene. This study also clarifies the mechanism of this effect on these cells. For this purpose, the cells harboring wild-type BCR/ABL, imatinib-resistant BCR/ABL (K562 and TCCYT315I), or Ba/F3 cells transfected with wild-type or mutant BCR/ABL genes were used. The results showed that MeST effectively inhibited the viability of leukemia cells in both a dose- and time-dependent manner. The effect of MeST seems to be more sensitive in the cells that carry imatinib-resistant BCR/ABL (especially the T315I BCR/ABL mutation) than those with wild-type BCR/ABL. Furthermore, we have demonstrated that the death caused by MeST is apoptosis and the treatment with MeST could suppress the expression of BCR/ABL, subsequently altering the downstream cascade of BCR/ABL such as AKT and MAPK signaling. In conclusion, MeST has been able to suppress the growth of leukemia cells harboring BCR/ABL. The mechanism of the anti-leukemic effect of MeST on cells harboring imatinib-resistant BCR/ABL mutations could be due to the disruption of the BCR/ABL oncoprotein signaling cascade.

Introdução: A dificuldade de uma avulsão dentária depende de cada situação clínica. No caso de uma extração difícil, geralmente, o operador utiliza instrumentos rotativos e convencionais. No entanto, com a evolução da tecnologia, foi introduzida a piezocirurgia, que se baseia no princípio da piezoeletricidade inversa. A mesma é 3 vezes mais potente que os instrumentos convencionais. Objetivo: O objetivo desta revisão sistémica é conhecer o funcionamento da piezocirurgia, a forma como pode ajudar durante a realização de uma avulsão complexa e os seus benefícios relativamente aos métodos tradicionais. Matérias e métodos: Foi realizada uma pesquisa na base de dados PubMed com a combinação de vários termos científicos. Através da pesquisa foram encontrados 108 artigos que, após a aplicação dos critérios de inclusão e exclusão, foram considerados relevantes apenas 22 artigos, sendo assim, incluídos nesta pesquisa. Resultados: Os artigos demonstram que existem várias vantagens do uso da piezocirurgia, tanto ao nível da capacidade de corte (micro vibrações, corte preciso e fino, sem grande pressão aplicada), como na conservação do osso e dos tecidos (seletividade do corte, risco de necrose diminuído, sistema de arrefecimento). Para além disto, é também benéfico para o bem-estar do paciente durante e pós-operatório (menos ruido). Conclusão: A piezocirurgia é caracterizada como uma tecnologia adequada na realização de avulsões complexas, devido aos seus benefícios. Sendo também utilizada nas diversas áreas da medicina.

Patents diagnosed with acute promyelocytic leukemia were treated with Vesanoid® [all-trans retinoic acid (ATRA)]. ATRA promotes the maturation and differentiation of leukemia cells and is therefore capable of reducing the symptoms of leukemia by preventing aggregation of myeloid cells. However, the clinical applications of ATRA are limited by its side effects, including acute retinoid resistance, hypertriglyceridemia, mucocutaneous dryness, nausea, brief recovery time relapse and drug resistance. Therefore, combinations of ATRA and other anticancer drugs are being investigated to overcome these limitations. In our previous study it was shown that in leukemia cells, (-)-epigallocatechin-3-gallate (EGCG) reduced cell proliferation and induced apoptotic cell death. In the present study, an in vitro evaluation of the effects of the combination of EGCG and ATRA on FLT3-mutated cell lines was performed using the isobologram method. The results showed that there was an additive effect in leukemic cells when treated with a combination of ATRA and EGCG. Thus, it was concluded that the cytotoxic effects of EGCG were improved by ATRA.

In our previous paper we previously reported that epigallocatechin-3-gallate (EGCG) inhibits FLT3 expression in cell lines harboring FLT3 mutations. In this research, we carried on to investigate the influence of EGCG on FLT3 promoter activity and FLT3 transcription. Methods The effect of EGCG on the mRNA expression of flt3 and flt3-promoter activity was evaluated using semiquantitative reverse transcription-PCR and luciferase reporter assay. The gene expression profiling analysis was done for detecting the effect of EGCG on flt3-transcription factors. Then, the protein level of C-MyB was obsvered using western blot analysis.The results showed that EGCG reduced the transcription level of FLT3 by suppressing its promoter activity. By doing gene expression profile analysis in MOLM-13 cells established from acute monocytic leukemia patient with two mutations within FLT3 EXON 14 in a time-dependent manner, we found that the expression of mRNA of FLT3 was first observed to downregulate at 6 h together with the decreasing of Homeobox A9 (HOXA9) transcription factor after EGCG treatment. The changing of C/EBPα expression was found at 8 h. Interestingly, the reducing mRNA of c-Myb by EGCG was observed at 4 h, earlier than FLT3 was downregulated. There was no change in Meis Homeobox 1 (Meis1) by EGCG. We also found the protein level c-Myb was inhibited by EGCG in MOLM-13 and MOLM-14 cells after treating these cells with 60µM of EGCG for 8 h.This data indicated the involvement of transcription factors in controlling the expression of FLT3 by EGCG.

There is a growing interest by governments and academics in including Indigenous knowledge alongside scientific knowledge in environmental management, including monitoring. Given this growing interest, a critical review of how Indigenous peoples have been engaged in monitoring is needed. We reviewed and analyzed the academic literature to answer the following questions: How have Indigenous peoples participated in environmental monitoring, and how has their participation influenced monitoring objectives, indicators, methods, and monitoring outcomes? We also summarized how this literature discussed power, governance, and the use of both Indigenous and scientific knowledge in environmental monitoring efforts. We found that the literature most often characterized participation as data collection, and that higher degrees of participation and power held by Indigenous peoples in environmental monitoring leads to initiatives that have different objectives, indicators, and outcomes than those with heavier involvement of external groups. Our review also showed that a key challenge of conducting effective monitoring that leverages both Indigenous knowledge systems and science is the power imbalances that uncouple Indigenous monitoring efforts from management. We encourage future initiatives to carefully consider the ways in which power and governance shape their programs and the ability of their monitoring to lead to meaningful management actions.

Objectives To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58–86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45–2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. Trial registration ClinicalTrials.gov Identifier: NCT04325893 ( https://clinicaltrials.gov/ct2/show/NCT04325893 ).

Postpartum depression (PPD) places a burden on maternal health. PPD exerts a negative impact on mothers’ health and children’s life. The purpose of this research was to identify the prevalence of PPD and the risk factors contributing to PPD. Therefore, a cross-sectional quantitative study was conducted. 116 women were categorized into two groups. One category included new mothers who received scores of Edinburgh Postpartum Depression Scale (EPDS) 12 or more. The other category included mothers who received scores less than 12. Descriptive statistic and then binary logistic regression were also performed. For EPDS ≥ 12, the prevalence of PPD was 27.6% among new mothers during the first year after delivery. Level of education, diseases during pregnancy, being the first-time mothers, dissatisfaction about family, and limited communication and interaction with others were significant predictors of PPD.