Diagnostic delay of myositis: an integrated systematic review.

BACKGROUND: Idiopathic inflammatory myopathies (IIM) are a heterogenous group of rare muscular autoimmune diseases characterised by skeletal muscle inflammation with possible diagnostic delay. Our aim was to review the existing evidence to identify overall diagnostic delay for IIM, factors associated with diagnostic delay, and people's experiences of diagnostic delay. METHODS: Three databases and grey literature sources were searched. Diagnostic delay was defined as the period between the onset of symptoms and the year of first diagnosis of IIM. We pooled the mean delay using random effects inverse variance meta-analysis and performed subgroup analyses. RESULTS: 328 titles were identified from which 27 studies were included. Overall mean diagnostic delay was 27.91 months (95% CI 15.03-40.79, I2 = 99%). Subgroup analyses revealed a difference in diagnostic delay between non-inclusion body myositis (IBM) and IBM types. There was no difference in diagnostic delay between studies in which myositis specific autoantibodies (MSA) were tested or not tested. In countries with gatekeeper health systems, where primary care clinicians authorize access to specialty care, people experienced longer periods of diagnostic delay than people with IIM in countries with non-gatekeeper systems. While studies discussed factors that may influence diagnostic delay, significant associations were not identified. No qualitative studies examining people's experiences of diagnostic delay were identified. CONCLUSION: Diagnostic delay of IIM has extensive impacts on the quality of life of people living with this disease. Understanding the experiences of people with IIM, from symptom onset to diagnosis, and factors that influence diagnostic delay is critical to inform clinical practice and training activities aimed at increasing awareness of this rare disease and expediting diagnosis. TRIAL REGISTRATION: PROSPERO Registration number: CRD42022307236 URL of the PROSPERO registration: https://www.crd.york.ac.uk/PROSPEROFILES/307236_PROTOCOL_20220127.pdf.

Diagnostic delay of myositis: protocol for an integrated systematic review.

INTRODUCTION: Idiopathic inflammatory myopathies (IIM). described as 'inflammatory myositis', are a heterogeneous group of rare muscular autoimmune diseases characterised by skeletal muscle inflammation. Its complex characteristics with lack of accurate diagnostic tests, unified classification system and comprehensive widely used diagnostic criteria could lead to diagnostic delay. This study will review diagnostic delay in myositis and provide an overview and clearer insight of patients' experiences, causes and consequences of diagnostic delay in myositis. METHODS AND ANALYSIS: The literature source will be a systematic search of PubMed/MEDLINE, Scopus, ProQuest and sources of grey literature, conducted from database inception to December 2021 without restrictions on publication date. All study types (qualitative and quantitative) except review articles, examining diagnostic delay, incorrect diagnosis, missed diagnosis or slow diagnosis of all types of myositis in all ages will be included. Evidence of patients' experiences associated with diagnostic delay will also be examined. Studies in languages other than English, German and Indonesian will be excluded. Outcomes will be diagnostic delay time, patients' experiences, and causes and consequences associated with diagnostic delay in myositis. Two review authors will independently screen the titles and abstracts of search results against the inclusion criteria. The Mixed Methods Appraisal Tool (MMAT) will be used to appraise selected studies. Two independent authors will extract data using a prepiloted data extraction tool. If sufficient quantitative data is available, a meta-analysis will be conducted along with subgroup analysis including pooled diagnostic delay in each type of myositis. Qualitative data will be analysed in line with meta-aggregation methods. If data is insufficient, a narrative synthesis will be conducted. ETHICS AND DISSEMINATION: As this work is a systematic review, ethical approval was not required. Findings of the study will be disseminated through publications in peer-reviewed journals, conferences and symposia. PROSPERO REGISTRATION NUMBER: CRD42022289830.

Coastal wetlands can be saved from sea level rise by recreating past tidal regimes.

Climate change driven Sea Level Rise (SLR) is creating a major global environmental crisis in coastal ecosystems, however, limited practical solutions are provided to prevent or mitigate the impacts. Here, we propose a novel eco-engineering solution to protect highly valued vegetated intertidal ecosystems. The new 'Tidal Replicate Method' involves the creation of a synthetic tidal regime that mimics the desired hydroperiod for intertidal wetlands. This synthetic tidal regime can then be applied via automated tidal control systems, "SmartGates", at suitable locations. As a proof of concept study, this method was applied at an intertidal wetland with the aim of restabilising saltmarsh vegetation at a location representative of SLR. Results from aerial drone surveys and on-ground vegetation sampling indicated that the Tidal Replicate Method effectively established saltmarsh onsite over a 3-year period of post-restoration, showing the method is able to protect endangered intertidal ecosystems from submersion. If applied globally, this method can protect high value coastal wetlands with similar environmental settings, including over 1,184,000 ha of Ramsar coastal wetlands. This equates to a saving of US$230 billion in ecosystem services per year. This solution can play an important role in the global effort to conserve coastal wetlands under accelerating SLR.

Elaeocarpus reticulatus fruit extracts reduce viability and induce apoptosis in pancreatic cancer cells in vitro.

Treatment options for pancreatic cancer (PC) are severely limited due to late diagnosis, early metastasis and the inadequacy of chemotherapy and radiotherapy to combat the aggressive biology of the disease. In recent years, plant-derived bioactive compounds have emerged as a source of novel, anti-cancer agents. Used in traditional medicine worldwide, Elaeocarpus species have reported anti-inflammatory, antioxidant and anti-cancer properties. This study aimed to isolate and identify potential anti-PC compounds in the fruit of Elaeocarpus reticulatus Sm. A 50% acetone crude extract significantly decreased the viability of four pancreatic cell lines (≥ 10 µg/mL for BxPC-3 cells) and induced apoptosis in BxPC-3 and HPDE cells. Analysis by HPLC identified the triterpenoid Cucurbitacin I as a likely component of the extract. Furthermore, treatment with Cucurbitacin I significantly reduced the viability of HPDE and BxPC-3 cells, with results comparable to the same concentration of gemcitabine. Interestingly, attempts to isolate bioactive compounds revealed that the crude extract was more effective at reducing PC-cell viability than the fractionated extracts. This study provides initial insight into the bioactive constituents of E. reticulatus fruits.

Fruit characteristics, phytochemical and antioxidant properties of blueberry ash (Elaeocarpus reticulatus).

Blueberry ash (Elaeocarpus reticulatus Sm.) fruit has potential for human nutrition, but there is limited information on this fruit. This preliminary study aimed to characterise blueberry ash fruit and examine the influence of extraction solvents on its phytochemical and antioxidant properties. Blueberry ash fruit is dark blue in colour and is a stone fruit of small size (7 mm) and light weight (0.2 g). However, it has a high portion of flesh (60% of fruit weight), which is edible and can be a potential source of phytochemicals. Water, ethanol, acetonitrile, acetone, and their combination were tested for extraction of phytochemicals from flesh of this fruit. Water or absolute organic solvent was ineffective for extraction of phenolic compounds from this fruit, but mixtures of water and organic solvents were more effective, and 50% acetone was the most suitable extraction solvent. Extraction with 50% acetone, this fruit was found to contain high levels of total phenolic content, flavonoids, proanthocyanidins, and anthocyanins (104 mg GAE/g, 155 mg RUE/g, 78 mg CE/g, and 119 mg CGE/g, respectively). In addition, this fruit was found to possess potent antioxidant properties. Therefore, this fruit should be further studied for identification of its phenolic compounds and further tested for their biological properties.

An Array of Bioactive Compounds From Australian Eucalypts and Their Relevance in Pancreatic Cancer Therapeutics.

Pancreatic cancer (PC) is one of the most devastating human cancers, and despite the significant advances in the current therapeutic options, the overall survival rate for PC has remained static for the past 50 years. Plant-derived bioactive compounds play a vital role in cancer therapeutics by providing new lead compounds for future drug development. Therefore, the isolation, characterization, and identification of new bioactive compounds for the prevention and treatment of cancer continue to be an important aspect of natural product research. Many in vitro and in vivo studies published in the last few decades have established strong links between the phytochemical profile of eucalypts and anticancer activity. However, only a small number of these reports have attempted to demonstrate a relationship between the biological activity of eucalypt extracts and PC. This review focuses on potential anti-PC effects of an array of bioactive compounds present in various species of eucalypts. It also highlights the necessity for further in vitro and in vivo studies to develop a complete understanding of the potential this group of plants has for the development of potent and specific chemotherapeutic drugs for PC.

Eucalyptus microcorys leaf extract derived HPLC-fraction reduces the viability of MIA PaCa-2 cells by inducing apoptosis and arresting cell cycle.

New therapeutic strategies such as the development of novel drugs and combinatorial therapies with existing chemotherapeutic agents are urgently needed to improve the clinical prognosis of pancreatic cancer. We have previously reported the antiproliferative properties of aqueous crude Eucalyptus microcorys extract against pancreatic cancer cell lines. In this study, bioassay-guided fractionation of the aqueous crude E. microcorys extract using RP-HPLC and subsequent assessment of the resultant fractions (F1-F5) for their antioxidant activity and cytotoxicity against pancreatic cancer cell lines were performed. The molecular mechanisms associated with the cytotoxicity was characterised by studying the effects of the most potent fraction-1 (F1) on apoptosis and cell cycle profiles as well as its phytochemical constituents by LC-ESI/MS/MS. F1 displayed significantly greater antioxidant activity in three different assays (p < 0.05). Moreover, F1 exhibited significantly greater antiproliferative activity (IC50 = 93.11 ±â€¯3.43 µg/mL) against MIA PaCa-2 cells compared to the other four fractions (p < 0.05). F1 induced apoptosis by regulating key apoptotic proteins- Bcl-2, Bak, Bax, cleaved PARP, procaspase-3 and cleaved caspase-3 in MIA PaCa-2 cells, suggesting the involvement of intrinsic mitochondrial apoptotic pathway and arrested cells at G2/M phase. A combination of gemcitabine and F1 exerted a greater effect on apoptosis and cell cycle arrest than F1 or gemcitabine alone (p < 0.05). LC-ESI/MS/MS revealed the tentative identities of phytochemicals present in F1 and their similarities with the phenolic compounds previously reported in Eucalyptus with antipancreatic cancer activity. Our study shows that the polyphenol and antioxidant-rich fraction of E. microcorys extract is a promising candidate for developing mono or combination therapies against pancreatic cancer.

In vitro anticancer properties of selected Eucalyptus species.

In spite of the recent advancements in oncology, the overall survival rate for pancreatic cancer has not improved over the last five decades. Eucalypts have been linked with cytotoxic and anticancer properties in various studies; however, there is very little scientific evidence that supports the direct role of eucalypts in the treatment of pancreatic cancer. This study assessed the anticancer properties of aqueous and ethanolic extracts of four Eucalyptus species using an MTT assay. The most promising extracts were further evaluated using a CCK-8 assay. Apoptotic studies were performed using a caspase 3/7 assay in MIA PaCa-2 cells. The aqueous extract of Eucalyptus microcorys leaf and the ethanolic extract of Eucalyptus microcorys fruit inhibited the growth of glioblastoma, neuroblastoma, lung and pancreatic cancer cells by more than 80% at 100 µg/mL. The E. microcorys and Eucalyptus saligna extracts showed lower GI50 values than the ethanolic Eucalyptus robusta extract in MIA PaCa-2 cells. Aqueous E. microcorys leaf and fruit extracts at 100 µg/mL exerted significantly higher cell growth inhibition in MIA PaCa-2 cells than other extracts (p < 0.05). Statistically similar IC50 values (p > 0.05) were observed in aqueous E. microcorys leaf (86.05 ± 4.75 µg/mL) and fruit (64.66 ± 15.97 µg/mL) and ethanolic E. microcorys leaf (79.30 ± 29.45 µg/mL) extracts in MIA PaCa-2 cells using the CCK-8 assay. Caspase 3/7-mediated apoptosis and morphological changes of cells were also witnessed in MIA PaCa-2 cells after 24 h of treatment with the extracts. This study highlighted the significance of E. microcorys as an important source of phytochemicals with efficacy against pancreatic cancer cells. Further studies are warranted to purify and structurally identify individual compounds and elucidate their mechanisms of action for the development of more potent and specific chemotherapeutic agents for pancreatic cancer.

Exploring the Least Studied Australian Eucalypt Genera: Corymbia and Angophora for Phytochemicals with Anticancer Activity against Pancreatic Malignancies.

While the pharmacological and toxicological properties of eucalypts are well known in indigenous Australian medicinal practice, investigations of the bioactivity of eucalypt extracts against high mortality diseases such as pancreatic cancer in Western medicine have to date been limited, particularly amongst the genera Corymbia and Angophora. Four Angophora and Corymbia species were evaluated for their phytochemical profile and efficacy against both primary and secondary pancreatic cancer cell lines. The aqueous leaf extract of Angophora hispida exhibited statistically higher total phenolic content (107.85 ± 1.46 mg of gallic acid equiv. per g) and total flavonoid content (57.96 ± 1.93 mg rutin equiv. per g) and antioxidant capacity compared to the other tested eucalypts (P < 0.05). Both A. hispida and A. floribunda aqueous extracts showed statistically similar saponin contents. Angophora floribunda extract exerted significantly greater cell growth inhibition of 77.91 ± 4.93% followed by A. hispida with 62.04 ± 7.47% (P < 0.05) at 100 µg/ml in MIA PaCa-2 cells with IC50 values of 75.58 and 87.28 µg/ml, respectively. More studies are required to isolate and identify the bioactive compounds from these two Angophora species and to determine their mode of action against pancreatic malignancies.

Botanical, Phytochemical, and Anticancer Properties of the Eucalyptus Species.

The genus Eucalyptus (Myrtaceae) is mainly native to Australia; however, some species are now distributed globally. Eucalyptus has been used in indigenous Australian medicines for the treatment of a range of aliments including colds, flu, fever, muscular aches, sores, internal pains, and inflammation. Eucalyptus oils containing volatile compounds have been widely used in the pharmaceutical and cosmetics industries for a multitude of purposes. In addition, Eucalyptus extracts containing nonvolatile compounds are also an important source of key bioactive compounds, and several studies have linked Eucalyptus extracts with anticancer properties. With the increasing research interest in Eucalyptus and its health properties, this review briefly outlines the botanical features of Eucalyptus, discusses its traditional use as medicine, and comprehensively reviews its phytochemical and anticancer properties and, finally, proposes trends for future studies.

Phytochemical, Antioxidant and Anti-Cancer Properties of Euphorbia tirucalli Methanolic and Aqueous Extracts.

Euphorbia tirucalli is a succulent shrub or small tree that is native to the African continent, however, it is widely cultivated across the globe due to its use in traditional medicines to treat ailments, ranging from scorpion stings to HIV. Recent studies have identified compounds present in the latex of the plant, including a range of bi- and triterpenoids that exhibit bioactivity, including anticancer activity. This study aimed to optimize water extraction conditions for high-yield total phenolic content recovery, to prepare methanol and aqueous extracts from the aerial sections of the plant, and to test the phytochemical, antioxidant, and anti-cancer properties of these extracts. Water extraction of total phenolic compounds (TPC) was optimized across a range of parameters including temperature, extraction time, and plant mass-to-solvent ratio. The water extract of the E. tirucalli powder was found to contain TPC of 34.01 mg GAE (gallic acid equivalents)/g, which was approximately half that of the methanol extract (77.33 mg GAE/g). The results of antioxidant assays showed a uniform trend, with the methanol extract's antioxidant reducing activity exceeding that of water extracts, typically by a factor of 2:1. Regression analysis of the antioxidant assays showed the strongest correlation between extract TPC and antioxidant activity for the ABTS (2,2-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) methods. The methanol extract also showed greater growth inhibition capacity towards the MiaPaCa-2 pancreatic cancer cell line. These data suggest that further investigations are required to confirm the source of activity within the E. tirucalli leaf and stems for potential use in the nutraceutical and pharmaceutical industries.