scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.

SMARCB1 Gene Therapy Using a Novel Tumor-Targeted Nanomedicine Enhances Anti-Cancer Efficacy in a Mouse Model of Atypical Teratoid Rhabdoid Tumors.

Purpose: Atypical teratoid rhabdoid tumor (ATRT) is a deadly, fast-growing form of pediatric brain cancer with poor prognosis. Most ATRTs are associated with inactivation of SMARCB1, a subunit of the chromatin remodeling complex, which is involved in developmental processes. The recent identification of SMARCB1 as a tumor suppressor gene suggests that restoration of SMARCB1 could be an effective therapeutic approach.

A Pralidoxime Nanocomplex Formulation Targeting Transferrin Receptors for Reactivation of Brain Acetylcholinesterase After Exposure of Mice to an Anticholinesterase Organophosphate.

Introduction: Organophosphates are among the deadliest of known chemicals based on their ability to inactivate acetylcholinesterase in neuromuscular junctions and synapses of the central and peripheral nervous systems. The consequent accumulation of acetylcholine can produce severe acute toxicities and death. Oxime antidotes act by reactivating acetylcholinesterase with the only such reactivator approved for use in the United States being 2-pyridine aldoxime methyl chloride (.

A Second Career for p53 as A Broad-Spectrum Antiviral?

As the world exits the global pandemic caused by the previously unknown SARS-CoV-2, we also mark the 30th anniversary of p53 being named "molecule of the year" by based on its role as a tumor suppressor. Although p53 was originally discovered in association with a viral protein, studies on its role in preventing carcinogenesis have far overshadowed research related to p53's role in viral infections. Nonetheless, there is an extensive body of scientific literature demonstrating that p53 is a critical component of host immune responses to viral infections.

A Novel P53 Nanomedicine Reduces Immunosuppression and Augments Anti-PD-1 Therapy for Non-Small Cell Lung Cancer in Syngeneic Mouse Models.

Lung cancer is among the most common and lethal cancers and warrants novel therapeutic approaches to improving patient outcomes. Although immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical benefits, most patients remain unresponsive to currently approved ICIs or develop resistance after initial response. Many ongoing clinical studies are investigating combination therapies to address the limited efficacy of ICIs.

Nanomedicine-Based Gene Delivery for a Truncated Tumor Suppressor RB94 Promotes Lung Cancer Immunity.

Because lung cancer remains the most common and lethal of cancers, novel therapeutic approaches are urgently needed. RB94 is a truncated form of retinoblastoma tumor suppressor protein with elevated anti-tumor efficacy. Our investigational nanomedicine (termed scL-RB94) is a tumor-targeted liposomal formulation of a plasmid containing the gene encoding RB94.

A Longitudinal Study of Chronic Periodontitis in Two Cohorts of Community-Dwelling Elderly Australians.

The study aimed to estimate and compare the incidence and progression of chronic periodontitis among two generations of older Australian adults. Data were from two population-based cohort studies of Australian older adults aged 60+ years South Australian Dental Longitudinal Studies (SADLS), SADLS I (1991-1992) and SADLS II (2013-2014). American Academy of Periodontology/the U.

"Eat clean, train mean, get lean": Body image and health behaviours of women who engage with fitspiration and clean eating imagery on Instagram.

The present study examined the relationship between posting or viewing fitspiration and clean eating imagery in relation to body image, disordered eating, and compulsive exercise among women. Participants (269 women aged 18-30 years) who posted and/or viewed fitspiration, clean eating or travel imagery on Instagram completed an online cross-sectional questionnaire. Results showed engaging with fitspiration and clean eating material (either posting or viewing) was significantly positively associated with increased levels of compulsive exercise and athletic-ideal internalization.

Population Impact of Sugar-Sweetened Beverages on Dental Caries and Overweight/Obesity in Australian Children.

The reported findings greatly consolidated evidence of detrimental effects of sugars intake on child oral health and overweight and obesity, some of the most prevalent chronic conditions in children. Evidence on population impact of sugars intake is directly informative to policy makers and the public about the potential impact of population-based programs targeting sugars intake to prevent dental caries and overweight and obesity.

Gene Therapy as a Potential Treatment for Patients with COVID-19.

SGT-53 is a novel investigational agent that comprises an immunoliposome carrying a plasmid vector driving expression of the human gene that encodes wild-type human p53. SGT-53 is currently in phase II human trials for advanced pancreatic cancer. Although p53 is best known as a tumor suppressor, its participation in both innate and adaptive immune responses is well documented.

Prevalence, extent, and severity of periodontitis among Australian older adults: Comparison of two generations.

Background: Chronic periodontitis is highly prevalent among older adults. The study aimed to compare periodontal disease among Australian older adults in two generations. We hypothesized that the prevalence and severity of periodontitis would decrease from the previous generation to the recent generation.

No likes, no problem? Users' reactions to the removal of Instagram number of likes on other people's posts and links to body image.

In the age of social media, "likes" are increasingly considered a numerical indicator of popularity and a measure of self-worth. Using an online questionnaire, Australian women (N = 291) aged 18-55 years self-reported their reaction to Instagram removing the visibility of the number of likes from other people's posts, and completed measures of comparison and body image. Findings showed that the majority of participants were in favour of the removal (66.

A systematic approach to quantitative Western blot analysis.

Attaining true quantitative data from WB requires that all the players involved in the procedure are quality controlled including the user. Appropriate protein extraction method, electrophoresis, and transfer of proteins, immunodetection of blotted protein by antibodies, and the ultimate step of imaging and analyzing the data is nothing short of a symphony. Like with any other technology in life-sciences research, Western blotting can produce erroneous and irreproducible data.

The prevalence and severity of root surface caries across Australian generations.

Background: The "failure of success" theory predicts that as subsequent generations of older adults retain more teeth, those additional teeth will experience more oral disease like root surface caries. The theory in relation to root surface caries has never been tested in a cross-generational study. This study aims to compare root surface caries across generations of South Australian older adults to test the theory and explore risk indicators for root surface caries.

A tumor-targeting nanomedicine carrying the p53 gene crosses the blood-brain barrier and enhances anti-PD-1 immunotherapy in mouse models of glioblastoma.

Despite its anticipated clinical potential, anti-PD-1 immunotherapy has only yielded poor outcomes in recent clinical trials for glioblastoma patients. Strategies combining anti-PD-1 antibody with other treatment modalities are being explored to alter the immunosuppressive microenvironment that appears to characterize these anti-PD-1-insensitive tumors. Here, we evaluated whether introducing wild-type p53 gene via a tumor-targeting nanomedicine (termed SGT-53) could provide immune stimulation and augment anti-PD-1 therapy in mouse syngeneic GL261 tumor models (either subcutaneous or intracranial).

Australia's sugar tale.

Objective: To establish high intake of free sugars and its related disease burden as a significant public health challenge in Australia.

Design: We discuss five key actions to reduce intake of free sugars tailored to the Australian context. These strategies are informed by reviewing the global scientific evidence on the effectiveness of a range of policy responses to reduce intake of free sugars at the population level.

Socioeconomic gradients in toothache experience among Australian adults: A time trend analysis from 1994 to 2013.

Objectives: To identify time trend pattern in toothache and to estimate whether toothache prevalence differs by socioeconomic position and residential location over time.

Methods: Data from nine successive National Dental Telephone Interview Surveys (NDTIS) from 1994 (n = 6907) to 2013 (n = 6778) performed in Australia among individuals aged 15 years or over were used. The dependent variable was toothache reported very often, often or sometimes during the previous 12 months.

Advancing Cancer Research in Africa Through Early-Career Awards: The BIG Cat Initiative.

Purpose: The burden of cancer in Africa is growing rapidly, and increased cancer research on the continent is a critical component of an effective response. In 2010, the US National Cancer Institute, in partnership with the African Organization for Research and Training in Cancer, launched the Beginning Investigator Grant for Catalytic Research (BIG Cat) initiative to support cancer research projects conducted by early-career African investigators.

Methods: To date, BIG Cat has provided 18 awards of up to $50,000 to support 2-year cancer research projects.

How much free sugar do Australians consume? Findings from a national survey.

Objective: To identify the characteristics of Australian adults exceeding the World Health Organization's free sugar (FS) intake recommendations of <10% and compare the sources of FS among those exceeding (high FS consumers) and complying (low FS consumers) with the recommendations.

Method: Nationally weighted data from the Australian National Nutrition and Physical Activity Survey 2011-12 was used to describe the proportions of FS consumption and sources of FS among adults aged ≥18 years (n=9,435) across demographic, socioeconomic and health behavioural subgroups. Six categories of food groups likely to contain FS were generated and analysed.

Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor.

The tumor suppressor p53 responds to genotoxic and oncogenic stresses by inducing cell cycle arrest and apoptosis. Recent studies suggest that p53 also participates in the regulation of cellular immune responses. Here, we have investigated the potential of p53 gene therapy to augment immune checkpoint inhibition by combining an anti-programmed cell death protein 1 (PD1) antibody with SGT-53, our investigational nanomedicine carrying a plasmid encoding human wild-type p53.

Different Myosin Head Conformations in Bony Fish Muscles Put into Rigor at Different Sarcomere Lengths.

At a resting sarcomere length of approximately 2.2 µm bony fish muscles put into rigor in the presence of BDM (2,3-butanedione monoxime) to reduce rigor tension generation show the normal arrangement of myosin head interactions with actin filaments as monitored by low-angle X-ray diffraction. However, if the muscles are put into rigor using the same protocol but stretched to 2.

Nanocomplex-based gene therapy promotes anti-tumor immunity through TP53- and STING-dependent mechanisms.

Loss or mutation of TP53 has been linked to alterations in anti-tumor immunity as well as dysregulation of cell cycle and apoptosis. We explored immunologic effects and mechanisms following restoration of wild-type human cDNA in murine oral cancer cells using the therapeutic nanocomplex scL-53. We demonstrated scL-53 induces dose-dependent expression of TP53 and induction of apoptosis and immunogenic cell death.

Determinants of knowledge and attitudes about sugar and the association of knowledge and attitudes with sugar intake among adults: A systematic review.

Efforts to reduce sugar intake levels have been primarily limited to increasing knowledge and changing attitudes. We conducted a systematic review to (1) identify factors influencing adults' knowledge and attitudes about sugar, and (2) determine if there is an association between knowledge and attitudes about sugar and sugar intake. We searched 15 electronic databases from inception to December 2016 for English language publications including adults with relevant exposure and outcome measures.

Investigating societal determinants of oral health-Opportunities and challenges in multilevel studies.

The high prevalence of oral diseases and the persistent nature of socioeconomic inequalities in oral health outcomes across societies presents a significant challenge for public health globally. A debate exists in epidemiology on the merits of investigating population variations in health and its determinants over studying individual health and its individual risk factors. The choice of analytical unit for health outcomes at the population level has policy implications and consequences for the causal understanding of population-level variations in health/disease.