Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer's Disease.

A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function.

An epigenetic predictor of death captures multi-modal measures of brain health.

Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities.

Childhood intelligence attenuates the association between biological ageing and health outcomes in later life.

The identification of biomarkers that discriminate individual ageing trajectories is a principal target of ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is 'DNAm PhenoAge'.

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron.

Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron.

Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts.

Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.

Promoting resilience in street connected young people in Guatemala: The role of psychological and educational protective factors.

Street connected young people (SCYP) are at risk of encountering negative life experiences, such as abuse, neglect, violence and exploitation. Nonetheless, some demonstrate remarkable resilience. This study therefore aimed to explore protective factors that promote resilience in SCYP in Guatemala City.

A 3,000-year-old Egyptian emmer wheat genome reveals dispersal and domestication history.

Tetraploid emmer wheat (Triticum turgidum ssp. dicoccon) is a progenitor of the world's most widely grown crop, hexaploid bread wheat (Triticum aestivum), as well as the direct ancestor of tetraploid durum wheat (T. turgidum subsp.

Hemodynamic Responses and G Protection Afforded by Three Different Anti-G Systems.

UK Royal Air Force fast jet aircrew use three different anti-G systems, however, little objective comparison of the G protection they provide exists. The G-protection afforded by each system and associated hemodynamic responses were investigated. Ten subjects performed centrifuge acceleration exposures using Mk-10 (S1) and Mk-4 (S2) five-bladder anti-G trousers (AGT) and full coverage AGT plus pressure breathing for G-protection (PBG; S3).

Gender-specific experiences of serious mental illness in rural Ethiopia: A qualitative study.

Considerable variation in the gender-specific prevalence of serious mental illness (SMI) has been reported in low- and middle-income countries (LMICs). In the rural setting of Butajira, Ethiopia, the male-to-female prevalence ratio of schizophrenia was reported to be 5:1. This qualitative study explores gender-specific experiences of SMI and the extent to which sociocultural factors may explain the observed difference in prevalence estimates.

Neighbourhood retail food outlet access, diet and body mass index in Canada: a systematic review.

Introduction: There is growing interest in the role of food environments in suboptimal diet and overweight and obesity. This review assesses the evidence for the link between the retail food environment, diet quality and body mass index (BMI) in the Canadian population.

Methods: We conducted a systematic keyword search in two bibliometric databases.

'Global mental health': systematic review of the term and its implicit priorities.

Background: The term 'global mental health' came to the fore in 2007, when the Lancet published a series by that name.

Aims: To review all peer-reviewed articles using the term 'global mental health' and determine the implicit priorities of scientific literature that self-identifies with this term.

Method: We conducted a systematic review to quantify all peer-reviewed articles using the English term 'global mental health' in their text published between 1 January 2007 and 31 December 2016, including by geographic regions and by mental health conditions.

Totally robotic right hemicolectomy: a multicentre case-matched technical and peri-operative comparison of port placements and da Vinci models.

The objective of the study was to review the technical and peri-operative outcomes using the da Vinci Xi (dVXi) and da Vinci Si (dVSi) models with suprapubic port placement (SPPP) or traditional port placements (TPP) during a robotic right hemicolectomy (RRHC). A retrospective review was undertaken of prospectively maintained databases of RRHC performed by two senior colorectal surgeons in the USA and Australia. Data were prospectively collected for patient demographics, intra-operative technical outcomes and peri-operative clinical outcomes.

Surgical techniques in the management of rectal cancer: a modified Delphi method by colorectal surgeons in Australia and New Zealand.

Background: Technological developments have allowed advances in minimally invasive techniques for total mesorectal excision such as laparoscopy, robotics, and transanal surgery. There remains an ongoing debate about the safety, benefits, and appropriate clinical scenarios for which each technique is employed. The aim of this study was to provide a panel of expert opinion on the role of each surgical technique currently available in the management of rectal cancer using a modified Delphi method.

Aircrew Conditioning Programme Impact on +Gz Tolerance.

Physical conditioning may improve aircrew performance during exposure to high +G acceleration, although few studies have directly assessed this. The present study investigated the effects of a 12-wk Aircrew Conditioning Programme (ACP) on markers of G tolerance. The ACP comprises aerobic and muscle strengthening exercise performed twice weekly and targets improved fitness and reduced injury risk.

Successful patient-oriented surgical outcomes in robotic vs laparoscopic right hemicolectomy for cancer - a systematic review.

Aim: Minimally invasive surgical approaches for cancer of the right colon have been well described with significant patient and equivalent oncological benefits. Robotic surgery has advanced in its ability to provide multi-quadrant abdominal access, leading the surgical community to widen its application outside of the pelvis to other abdominal compartments. Globally it is being realized that a patient's surgical episode of care is becoming the epicentre of cancer treatment.

Integrated Model for Patient-Centered Advanced Liver Disease Care.

Advanced liver disease (AdvLD) is a high-risk common condition with a progressive, highly morbid, and often fatal course. Despite effective treatments, there are substantial shortfalls in access to and use of evidence-based supportive and palliative care for AdvLD. Although patient-centered, chronic illness models that integrate early supportive and palliative care with curative treatments hold promise, there are several knowledge gaps that hinder development of an integrated model for AdvLD.

Assessment and Comparison of Molecular Subtyping and Characterization Methods for .

The food industry is facing a major transition regarding methods for confirmation, characterization, and subtyping of . Whole-genome sequencing (WGS) is rapidly becoming both the method of choice and the gold standard for subtyping; however, routine use of WGS by the food industry is often not feasible due to cost constraints or the need for rapid results. To facilitate selection of subtyping methods by the food industry, we present: (i) a comparison between classical serotyping and selected widely used molecular-based subtyping methods including pulsed-field gel electrophoresis, multilocus sequence typing, and WGS (including WGS-based serovar prediction) and (ii) a scoring system to evaluate and compare subtyping assays.

Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936.

Although plasma proteins may serve as markers of neurological disease risk, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. Therefore, we conduct genome- and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750 healthy older adults). We identify 41 independent genome-wide significant (P < 5.

Posterior wall acetabular fracture fixation: A mechanical analysis of fixation methods.

Stable, anatomical fixation of acetabular fractures gives the best chance of successful outcome, while penetration of the acetabular articular surface with screws is associated with poor outcomes. Spring plates are an alternative to interfragmentary lag screws when penetration is a concern. A mechanical study comparing fracture stability and construct stiffness of three fixation methods for posterior wall acetabular fractures with transverse comminutions was performed.

Degenerative Cervical Myelopathy: A 7-Letter Coding System That Supports Decision-Making for the Surgical Approach.

Objective: To validate with a prospective study a decision-supporting coding system for the surgical approach for multilevel degenerative cervical myelopathy.

Methods: Ten cases were presented on an internet platform, including clinical and imaging data. A single-approach (G1), a choice between 2 (G2), or 3 approaches (G3) were options.

Clinical Evaluation of Intraoperative Near Misses in Laparoscopic Rectal Cancer Surgery.

Objective: To investigate the frequency, nature, and severity of intraoperative adverse near miss events within advanced laparoscopic surgery and report any associated clinical impact.

Background: Despite implementation of surgical safety initiatives, the intraoperative period is poorly documented with evidence of underreporting. Near miss analyses are undertaken in high-risk industries but not in surgical practice.