Publications by authors named "Browne C"

Introduction: Capnocytophaga is a genus of bacteria that are commensal to the oral microbiome of humans and some animals. Some Capnocytophaga species are found in the human oral cavity and rarely cause disease in people; the species found in animals are zoönotic and can be transmitted to people via saliva. This study describes the clinical and epidemiologic features of patients from whom Capnocytophaga spp.

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Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J.

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Background: Sex workers' risk of violence and ill-health is shaped by their work environments, community and structural factors, including criminalisation.

Aim: We evaluated the impact of removing police enforcement on sex workers' safety, health and access to services.

Design: Mixed-methods participatory study comprising qualitative research, a prospective cohort study, mathematical modelling and routine data collation.

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The Omura's whale () is one of the most recently described species of baleen whale. Initially known only from stranding and whaling specimens, it has now been identified in all ocean basins excluding the central and eastern Pacific. Unlike most baleen whales that migrate between the poles and the equator seasonally, the Omura's whale is known to inhabit tropical to sub-tropical waters year-round.

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Extraction of proteins from the membrane using styrene maleic acid co-polymers (SMA), forming SMA lipid particles (SMALPs), has allowed for the first time the purification of membrane proteins with their lipid bilayer environment. To date, SMA2000 has been the most effective polymer used for this purpose, with a 2:1 ratio of styrene:maleic acid, and styrene and maleic acid moieties spread statistically throughout the chain. However, SMA2000 is a highly polydisperse polymer that contains an array of different polymer lengths and sequences.

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Objective: To characterise the effect of solitary and serial manual bolus irrigations on intrarenal pressures (IRPs) and observe the clinical consequences.

Patients And Methods: A pressure guidewire was used for IRP measurement during routine flexible ureterorenoscopy for management of renal stone disease, including manual bolus irrigation when required to maintain vision. The fluid bolus was either as a solitary manual bolus or a series of manual boluses in quick succession.

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Article Synopsis
  • Chronic exposure to cocaine leads to lasting changes in the brain's genetic structure, particularly in the nucleus accumbens, which plays a key role in motivation and addiction.
  • After withdrawing from cocaine, the depletion of a specific histone variant (H2A.Z) occurs, resulting in increased gene expression linked to relapse behavior among certain neurons (D1 MSNs).
  • The study highlights how the chaperone ANP32E regulates H2A.Z removal, suggesting potential therapeutic targets for preventing the negative effects of cocaine on brain function and behavior.
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Liquid-liquid phase separation, whereby two liquids spontaneously demix, is ubiquitous in industrial, environmental, and biological processes. While isotropic fluids are known to condense into spherical droplets in the binodal region, these dynamics are poorly understood for structured fluids. Here, we report the unique observation of condensate networks, which spontaneously assemble during the demixing of a mesogen from a solvent.

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Purpose: A shortage of essential intravenous (IV) etoposide lasted from 2018 until 2020 in Ontario, Canada, allowing for a natural experiment in which external factors (IV etoposide availability) dictated patients' treatment assignment. The purpose of this study was to evaluate the impact of this IV etoposide shortage (IVES) on patient care outcomes.

Methods: Individuals with extensive-stage small-cell lung cancer (ES-SCLC) treated during a pre-IVES (November 2017-October 2018) and IVES (November 2018-October 2019) time intervals were retrospectively reviewed at the Verspeeten Family Cancer Centre.

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Article Synopsis
  • The study highlights a significant disparity in mental health prevalence, showing that a higher percentage of prisoners in Australia and New Zealand suffer from mental illness compared to the general population.
  • A meta-analysis of 17 studies revealed that about 69% of prisoners have experienced some form of mental illness over their lifetime, with 9.1% specifically having psychotic disorders.
  • The findings indicate a concerning rise in the rates of psychosis over time, suggesting a need for better mental health interventions and diversion strategies to steer affected individuals away from the criminal justice system and into appropriate healthcare.
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Due to their interactions with the neurovasculature, microglia are implicated in maladaptive responses to hypobaric hypoxia at high altitude (HA). To explore these interactions at HA, pharmacological depletion of microglia with the colony-stimulating factor-1 receptor inhibitor, PLX5622, was employed in male C57BL/6J mice maintained at HA or sea level (SL) for 3-weeks, followed by assessment of ex-vivo hippocampal long-term potentiation (LTP), fear memory recall and microglial dynamics/physiology. Our findings revealed that microglia depletion decreased LTP and reduced glucose levels by 25% at SL but did not affect fear memory recall.

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Anhedonia and avolition are emotions frequently endorsed by individuals with stress related disorders. Kappa opioid receptor (KOR) activation can induce negative emotions and recent clinical evidence suggests that KOR antagonism can alleviate anhedonia in a transdiagnostic cohort of patients. However, the behavioral consequences of KOR activation and antagonism in modulating motivation, as assessed by schedule-controlled behavioral performance without preexisting conditions (stress or substance use), have not been formally assessed.

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Article Synopsis
  • IRAK4 is a key player in IL-1R and TLR signaling, making it a target for treating autoimmune diseases.
  • Researchers developed KT-474, a powerful and selective IRAK4 degrader that can be taken orally, marking it as the first of its kind tested outside of cancer treatment.
  • KT-474 has completed phase I trials in healthy individuals and patients with skin conditions, and has advanced to phase II trials for further evaluation.
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Purpose: Despite the high rates of psychotic disorders amongst people in prison, current prison mental health screening approaches have not included assessment of the full psychosis spectrum to capture those at-risk of an emerging psychosis as well as those with established illness nor assessed the concurrent validity of psychosis symptom screening.

Methods: Using a clinical staging approach to establish the prevalence of Ultra High Risk (UHR), first episode of psychosis (FEP) and established psychosis (EP) groups, 291 adults entering custody in two prison reception centres in NSW completed a two-stage (screening and validation) interview process. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to determine the clinical stages of psychosis and concurrent validity of symptom screening in identifying individuals on the psychosis spectrum was formally assessed.

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Small-cell lung cancer (SCLC) remains a disease with poor prognosis, particularly in extensive-stage SCLC (ES-SCLC). Current standard-of-care treatment includes chemotherapy with platinum agents and etoposide plus immunotherapy with atezolizumab or durvalumab, which has achieved a mean overall survival of 12-13 months in clinical trials. However, long-term survival in ES-SCLC, even with the addition of immunotherapy, continues to be rare.

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The development of drug addiction is characterized by molecular changes in brain reward regions that lead to the transition from recreational to compulsive drug use. These neurobiological processes in brain reward regions, such as the nucleus accumbens (NAc), are orchestrated in large part by transcriptional regulation. Our group recently identified the transcription factor E2F3a as a novel regulator of cocaine's rewarding effects and gene expression regulation in the NAc of male mice.

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Turbulent flows have been used for millennia to mix solutes; a familiar example is stirring cream into coffee. However, many energy, environmental, and industrial processes rely on the mixing of solutes in porous media where confinement suppresses inertial turbulence. As a result, mixing is drastically hindered, requiring fluid to permeate long distances for appreciable mixing and introducing additional steps to drive mixing that can be expensive and environmentally harmful.

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Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region.

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Article Synopsis
  • * Researchers have developed KT-413, a novel dual-function molecule that effectively degrades IRAK4 and key transcription factors, Ikaros and Aiolos, to combat this subtype of lymphoma.
  • * KT-413 has shown promising results in preclinical studies, leading to the initiation of a phase 1 clinical trial targeting B-cell lymphomas, particularly those with MYD88 mutations.
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Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation.

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Background: The nursing workforce faces significant stressors every day that can lead to exhaustion and burnout. The unprecedented challenges that were faced during the Covid-19 pandemic, placed an added burden on nurses who were already under pressure. Nurses were at the frontline of care provision, and nursing leaders had to rapidly implement strategies to support and maintain staff safety, short and long-term well-being.

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Drugs of abuse are thought to promote addiction in part by "hijacking" brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type-specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified as a molecular substrate that regulates cell type-specific signal transduction in NAc while enabling drugs to suppress natural reward consumption.

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Article Synopsis
  • Major depressive disorder (MDD) is associated with changes in brain structure and synaptic function, particularly in limbic regions.
  • Astrocytes, brain cells affected by chronic stress, show altered gene profiles that may play a role in these changes, especially in the nucleus accumbens (NAc).
  • The study found that a specific astrocyte-produced protease gene is downregulated in males and upregulated in females, revealing sex-specific responses to stress and offering potential new targets for MDD treatment.
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