Emerging therapeutic potential of nanoparticles in pancreatic cancer: a systematic review of clinical trials

Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009

Multidisciplinary discovery of ancient restoration using a rare mud carapace on a mummified individual from late New Kingdom Egypt.

Funder: Rundle Foundation for Egyptian ArchaeologyCT scans of an unnamed mummified adult from Egypt, now in the Chau Chak Wing Museum, University of Sydney (NMR.27.3), reveal it to be fully sheathed in a mud shell or carapace, exposing a mortuary treatment not previously documented in the Egyptian archaeological record. The carapace was placed between layers of linen wrappings thus it was not externally visible. Radiocarbon dating of textile samples provide a range of c.1370-1113 cal BC (95.4% probability), with a median date of 1207 cal BC. When assessed against mummification techniques of the era, the individual is placed in the late 19th-20th Dynasty, at the later end of this date range. Multi-proxy analysis including μ-XRF and Raman spectroscopy of carapace fragments from the head area revealed it to consist of three layers, comprising a thin base layer of mud, coated with a white calcite-based pigment and a red-painted surface of mixed composition. Whether the whole surface of the carapace was painted red is unknown. The carapace was a form of ancient conservation applied subsequent to post-mortem damage to the body, intended to reconfigure the body and enable continued existence of the deceased in the afterlife. The carapace can also be interpreted as a form of elite emulation imitating resin shells found within the wrappings of royal bodies from this period

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART

Emerging therapeutic potential of nanoparticles in pancreatic cancer: a systematic review of clinical trials

Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD4201502000

Trends in soil carbon and nutrients of hill-country pastures receiving different phosphorus fertilizer loadings for 20 years

There are few records of long-term trends in soil C and N in grazed pasture systems but recent measurements have demonstrated unexplained losses on New Zealand lowlands. To determine whether losses were also occurring in hill country pastures, we analyzed archived soil samples collected between 1983 and 2006 from two slope classes (steep and easy) at the Whatawhata Research Centre. Soils were Ultic Hapludand and Typic Haplohumult on the easy slopes (10–20°), and Typic Haplohumult on the steeper slopes (30–40°). Soil samples (0–75 mm) had been collected from paddocks that were fertilized with six different loading rates of P (ranging from 0 to 100 kg P ha⁻¹ year⁻¹ since 1985). This range of P loadings allowed us to determine whether P inputs would regulate trends in soil C and N. While there were significant temporal trends in C and N (P < 0.05), these were not unidirectional and trends were not dependent on P loading rate. On average, soil C initially increased during the first 6 years of the trial at 0.270% C year⁻¹ (1.56 t ha⁻¹ year⁻¹) and 0.156% C year⁻¹ (1.06 t ha⁻¹ year⁻¹) on easy and steep slopes, respectively. Subsequently, there was no significant trend in soil C on the easy slopes but soil C declined at −0.066% year⁻¹ (0.45 t ha⁻¹ year⁻¹) on the steep slopes. Similarly, soil N increased between 1983 and 1989 at 0.025% N year⁻¹ (144 kg ha⁻¹ year⁻¹) and 0.012% N year⁻¹ (82 kg ha⁻¹ year⁻¹) on easy and steep slopes, respectively. Post-1989, small but significant losses of total N were measured on the steep slopes of 0.004% year⁻¹ (27 kg N ha⁻¹ year⁻¹) (P < 0.05) with no trend on the easy slopes. Two potential causal factors for these decadal-scale patterns were identified, operating via changes in primary productivity. These were lower S inputs from 1989 due to a change in fertilizer type, and a series of relatively dry summers during the 1990s. These significant inter-annual trends in soil C and N complicate attempts to measure long-term changes in soil organic matter associated with land use change and management practices. This study has demonstrated the potential error associated with infrequent soil sampling to determine long-term trends in soil C and N; large gains or losses could have been detected at Whatawhata depending on when sampling started and finished. Understanding these long-term trends in soil organic matter dynamics and driving factors requires more long-term sampling trials

Multidisciplinary discovery of ancient restoration using a rare mud carapace on a mummified individual from late New Kingdom Egypt.

CT scans of an unnamed mummified adult from Egypt, now in the Chau Chak Wing Museum, University of Sydney (NMR.27.3), reveal it to be fully sheathed in a mud shell or carapace, exposing a mortuary treatment not previously documented in the Egyptian archaeological record. The carapace was placed between layers of linen wrappings thus it was not externally visible. Radiocarbon dating of textile samples provide a range of c.1370-1113 cal BC (95.4% probability), with a median date of 1207 cal BC. When assessed against mummification techniques of the era, the individual is placed in the late 19th-20th Dynasty, at the later end of this date range. Multi-proxy analysis including μ-XRF and Raman spectroscopy of carapace fragments from the head area revealed it to consist of three layers, comprising a thin base layer of mud, coated with a white calcite-based pigment and a red-painted surface of mixed composition. Whether the whole surface of the carapace was painted red is unknown. The carapace was a form of ancient conservation applied subsequent to post-mortem damage to the body, intended to reconfigure the body and enable continued existence of the deceased in the afterlife. The carapace can also be interpreted as a form of elite emulation imitating resin shells found within the wrappings of royal bodies from this period

Evidence-based practice in speech-language pathology curricula: a scoping study

This scoping study investigated how evidence-based practice (EBP) principles are taught in Australian speech-language pathology (SLP) teaching and learning contexts. It explored how Australian SLP university programs: (1) facilitate student learning about the principles of EBP in academic and clinical settings, and (2) self-evaluate their curricula in relation to EBP. The research involved two surveys. Survey 1 respondents were 131 academic staff, program coordinators, and on-campus and off-campus clinical educators. This survey gathered information about EBP teaching and learning in SLP programs as well as future EBP curriculum plans. Survey 2 investigated how clinical educators incorporated EBP into the way they taught clinical decision-making to students. Surveys responses from 85 clinical educators were analysed using descriptive and nonparametric statistics and thematic grouping of open-ended qualitative responses. Both surveys revealed strengths and gaps in integrating EBP into Australian SLP curricula. Perceived strengths were that respondents were positive about EBP, most had EBP training and access to EBP resources. The perceived gaps included the academic staff’s perceptions of students’ understanding and application of EBP, respondents’ understanding of research methodologies, communication and collaboration between academic staff and clinical educators, and a lack of explicit discussion by clinical educators and students of EBP in relation to clients

Dental pathology in the Circle: oral health, activity and intervention in Neolithic Malta

The ERC-funded FRAGSUS Project (Fragility and sustainability in small island environments: adaptation, culture change and collapse in prehistory, 2013–18) led by Caroline Malone has focused on the unique Temple Culture of Neolithic Malta and its antecedents. This third volume builds on the achievements of Mortuary customs in prehistoric Malta, published by the McDonald Institute in 2009. It seeks to answer many questions posed, but left unanswered, of the more than 200,000 fragments of mainly commingled human remains from the Xagħra Brochtorff Circle on Gozo. The focus is on the interpretation of a substantial, representative subsample of the assemblage, exploring dentition, disease, diet and lifestyle, together with detailed understanding of chronology and the affinity of the ancient population associated with the ‘Temple Culture’ of prehistoric Malta. The first studies of genetic profiling of this population, as well as the results of intra-site GIS and visualization, taphonomy, health and mobility, offer important insights into this complex mortuary site and its ritual. Remarkable evidence on the bioanthropology of care practised by these populations, together with a relatively low level of interpersonal violence, and examples of longevity, reveal new aspects about the Neolithic Maltese. Detailed case studies employing computerized tomography describe disease such as =scurvy and explore dietary issues, whilst physical activity and body size have been assessed through biomechanical analysis, supported by taphonomic study, isotopic analyses, a review of mortuary practices during prehistory and a robust new chronology. The results form a rich contextualized body of material that advances understanding of cultural change within the context of small island insularity, and provides biological comparisons for the graphic figurative art of early Malta. These data and the original assemblage are conserved in the National Museum of Archaeology in Valletta as a resource for future study.This project has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7-2007-2013) (Grant agreement No. 323727)