Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.

Rationale: G-protein biased mu-opioid receptor (MOR) agonists have been reported to exhibit superior therapeutic windows compared to prototypical MOR agonists when relating antinociception to respiratory depression. However, there is relatively little research on the abuse potential of G-protein biased MOR agonists in relation to other behavioral endpoints.

Objectives: The aim of the present study was to quantitatively compare the reinforcing, antinociceptive, and respiratory-depressant effects of the prototypical MOR agonists, fentanyl and oxycodone, to the G-protein biased MOR agonists, SR14968 and SR17018, in male and female rats.

Mycoplasma genitalium retrospective audit of Northern Territory isolates from 2022.

The Northern Territory (NT) has the highest rates of sexually transmitted infections (STI) in Australia; however, the local prevalence of () has not been previously determined. This study was designed to review detection, to determine the regional NT prevalence and macrolide resistance rates. In our study the NT background prevalence of is 13%, with the highest detection rates occurring in central Australia and in correctional facility inmates.

Transcription factor 4 is a key mediator of oncogenesis in neuroblastoma by promoting MYC activity.

Super-enhancer-associated transcription factor networks define cell identity in neuroblastoma (NB). Dysregulation of these transcription factors contributes to the initiation and maintenance of NB by enforcing early developmental identity states. We report that the class I basic helix-loop-helix (bHLH) transcription factor 4 (TCF4; also known as E2-2) is a critical NB dependency gene that significantly contributes to these identity states through heterodimerization with cell-identity-specific bHLH transcription factors.

Altered epidemiological patterns of Respiratory Syncytial Virus and influenza detections in a tropical Australian setting 2020 to 2023.

Background: We describe the recent temporal patterns of respiratory syncytial virus (RSV) and influenza virus detections in the Northern Territory (NT) of Australia, between 2020 and 2023.

Methods: This retrospective analysis of patients presenting with respiratory diseases utilised a multiplex viral nucleic acid detection assay for RSV, influenza and SARS Cov2 (COVID-19) to determine the relative frequency of non-COVID-19 respiratory viral detections by age and month during the study period.

Results: During this period of the NT COVID-19 epidemic, disruption of the usual annual wet season RSV outbreak patterns occurred, and the yearly influenza peak was absent for two annual cycles.

Assessment of the antinociceptive, respiratory-depressant, and reinforcing effects of the low pK fluorinated fentanyl analogs, FF3 and NFEPP.

Rationale: Recent studies report that fentanyl analogs with relatively low pK values produce antinociception in rodents without other mu opioid-typical side effects due to the restriction of their activity to injured tissue with relatively low pH values. However, it is unclear if and to what degree these compounds may produce mu opioid-typical side effects (respiratory depression, reinforcing effects) at doses higher than those required to produce antinociception.

Objectives: The present study compared the inflammatory antinociceptive, respiratory-depressant, and reinforcing effects of fentanyl and two analogs of intermediate (FF3) and low (NFEPP) pK values in terms of potency and efficacy in male and female Sprague-Dawley rats.

Comprehensive observational study evaluating the enduring effectiveness of 4CMenB, the meningococcal B vaccine against gonococcal infections in the Northern Territory and South Australia, Australia: study protocol.

Introduction: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, and that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections.

Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma.

Neuroblastoma with MYCN amplification (MNA) is a high-risk disease that has a poor survival rate. Neuroblastoma displays cellular heterogeneity, including more differentiated (adrenergic) and more primitive (mesenchymal) cellular states. Here, we demonstrate that MYCN oncoprotein promotes a cellular state switch in mesenchymal cells to an adrenergic state, accompanied by induction of histone lysine demethylase 4 family members (KDM4A-C) that act in concert to control the expression of MYCN and adrenergic core regulatory circulatory (CRC) transcription factors.

Contingent administration of typical and biased kappa opioid agonists reduces cocaine and oxycodone choice in a drug vs. food choice procedure in male rhesus monkeys.

Rationale: Combinations of mu and kappa-opioid receptor (KOR) agonists have been proposed as analgesic formulations with reduced abuse potential. The feasibility of this approach has been increased by the development of KOR agonists with biased signaling profiles that produce KOR-typical antinociception with fewer KOR-typical side effects.

Objective: The present study determined if the biased KOR agonists, nalfurafine and triazole 1.

Psychosis secondary to thyrotoxicosis that persisted post-thyroidectomy: a case report.

Background: This case report is of a patient with psychosis secondary to thyrotoxicosis that persisted and reemerged after definitive treatment of thyroidectomy, which is a unique occurrence in the literature.

Case Presentation: This patient is a male between 30 and 35 years of age with a history of Graves Disease and no past psychiatric history who was admitted to the hospital due to psychosis secondary to thyrotoxicosis. The thyrotoxicosis was treated with surgical removal, but the psychotic symptoms persisted after surgery and normalization of standard thyroid functional measures.

Increased hippocampal cannabinoid 1 receptor expression is associated with protection from severe seizures in pregnant mice with reduced uterine perfusion pressure.

Eclampsia, new-onset seizures in pregnancy, can complicate preeclampsia, a hypertensive pregnancy disorder. The mechanisms contributing to increased risk of seizures in preeclampsia are not fully known. One mechanism could be abnormal endocannabinoid system (ECS) activity and impaired neuromodulation.

Quantification of observable behaviors following oral administration of oxycodone and nalfurafine in male rhesus monkeys.

Background: Recent preclinical studies have investigated the atypical kappa-opioid receptor (KOR) agonist, nalfurafine, as a co-formulary with mu-opioid receptor (MOR) agonists as a potential deterrent for misuse. However, no study has investigated effects of nalfurafine combined with a MOR agonist using an oral route of administration. The objective of the current study was to measure behavioral effects of orally administered oxycodone and nalfurafine, alone and combined, in rhesus monkeys using a quantitative behavioral observation procedure.

Comparison of Melioidosis Indirect Hemagglutination Assay between Three Testing Laboratories in Australia.

Melioidosis caused by Burkholderia pseudomallei causes significant morbidity and mortality in Southeast Asia and northern Australia. Clinical manifestations remain diverse, including localized skin infection, pneumonia, and chronic abscess formation. Culture remains the gold standard of diagnosis, with serology and antigen detection tests playing a role if culture is unfeasible.

Detection of Influenza in Managed Quarantine in Australia and the Estimated Risk of Importation.

Background: Influenza circulated at historically low levels during 2020/2021 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic travel restrictions. In Australia, international arrivals were required to undergo a 14-day hotel quarantine to limit new introduction of SARS-CoV-2.

Methods: We usedtesting data for travelers arriving on repatriation flights to Darwin, Australia, from 3 January 2021 to 11 October 2021 to identify importations of influenza virus into Australia.

Effects of methadone, buprenorphine, and naltrexone on actigraphy-based sleep-like parameters in male rhesus monkeys.

Opioid use disorder (OUD) has been associated with the emergence of sleep disturbances. Although effective treatments for OUD exist, evidence suggests that these treatments also may be associated with sleep impairment. The extent to which these effects are an effect of OUD treatment or a result of chronic opioid use remains unknown.

Epidemiological and clinical characteristics of legionellosis in Northern Australia, 2010-2021.

Objective: This study describes characteristics of the legionellosis cases occurring between 2010 and 2021 in the Northern Territory (NT), Australia.

Methods: We retrospectively reviewed 53 cases of legionellosis during the defined period and documented patient and clinical characteristics, diagnostics, and seasonality of infection.

Results: All cases were sporadic.

The G-protein biased kappa opioid agonists, triazole 1.1 and nalfurafine, produce non-uniform behavioral effects in male rhesus monkeys.

Kappa-opioid receptor (KOR) agonists have been studied as potential treatments for pain, pruritus, and substance-use disorders, but prototypical KOR agonists produce side-effects like dysphoria and sedation. Atypical KOR agonists that exhibit G-protein biased signaling at the KOR have been reported to produce therapeutic-like effects with fewer or reduced side effects relative to prototypical KOR agonists. In the current report, behavioral profiles were determined using a behavioral scoring system that was modified to quantify drug-induced behaviors in nonhuman primates (NHPs).

Genomic Evidence of In-Flight SARS-CoV-2 Transmission, India to Australia, April 2021.

Epidemiologic and genomic investigation of SARS-CoV-2 infections associated with 2 repatriation flights from India to Australia in April 2021 indicated that 4 passengers transmitted SARS-CoV-2 to >11 other passengers. Results suggest transmission despite mandatory mask use and predeparture testing. For subsequent flights, predeparture quarantine and expanded predeparture testing were implemented.

Treatment-resistant depression with anhedonia: Integrating clinical and preclinical approaches to investigate distinct phenotypes.

In our clinical work with treatment-resistant depressed (TRD) patients, certain patterns have emerged in terms of patients' presentations of anhedonia. Multiple studies have investigated anhedonia either as a state or a trait variable in depression, but anhedonia is a multifaceted construct and, as we better understand anhedonia, we increase our ability to measure and treat it. With the aim of personalizing medicine for more efficacious treatments, this paper focuses on clinical patterns we have seen in anhedonic TRD and argues for studies to be done in support of translational, face, and construct validity.

Choice between food and cocaine reinforcers under fixed and variable schedules in female and male rhesus monkeys.

Illicit drugs like cocaine may be uncertain in terms of the time and effort required to obtain them. Behavior maintained by variable schedules resembles excessive drug-taking compared with fixed schedules. However, no prior research has examined fixed versus variable schedules in drug versus nondrug choice.

Therapeutically targeting oncogenic CRCs facilitates induced differentiation of NB by RA and the BET bromodomain inhibitor.

Retinoic acids (RAs) are the most successful therapeutics for cancer differentiation therapy used in high-risk neuroblastoma (NB) maintenance therapy but are limited in effectiveness. This study identifies a strategy for improving efficacy through disruption of cancer cell identity via BET inhibitors. Mutations that block development are theorized to cause NB through retention of immature cell identities contributing to oncogenesis.

The kappa-opioid receptor agonist, triazole 1.1, reduces oxycodone self-administration and enhances oxycodone-induced thermal antinociception in male rats.

Rationale: Triazole 1.1 is a novel kappa-opioid receptor (KOR) agonist reported to produce antinociception without KOR-typical adverse effects. When combined with the mu-opioid receptor (MOR) agonist, oxycodone, triazole 1.