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Abstract Introduction In Viet Nam, key populations (KPs) face barriers accessing HIV services. Virtual platforms can be leveraged to increase access for KPs, including for HIV self‐testing (HIVST). This study compares reach and effectiveness of a web‐based HIVST intervention from pilot to scale‐up in Viet Nam. Methods A mixed‐methods explanatory sequential design used cross‐sectional and thematic analysis. The pilot launched in Can Tho in November 2020, followed by Hanoi and Nghe An in April 2021. Scale‐up included Can Tho and Nghe An, with 21 novel provinces from April to December 2022. After risk assessment, participants registered on the website, receiving HIVST (OraQuick®) by courier, peer educator or self‐pick‐up. Test result reporting and completing satisfaction surveys were encouraged. Intervention reach was measured through numbers accessing the testing, disaggregated by demographics, and proportion of individuals reporting self‐testing post‐registration. Effectiveness was measured through numbers reporting self‐test results, testing positive and linking to care, and testing negative and using HIVST to manage pre‐exposure prophylaxis (PrEP) use. Thematic content analysis of free‐text responses from the satisfaction survey synthesized quantitative outcomes. Results In total, 17,589 participants registered on the HIVST website; 11,332 individuals ordered 13,334 tests. Participants were generally young, aged

Background: Androgen-deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations., Methods: The authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT., Results: In total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health-related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008-2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing., Conclusions: Most patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment-related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment-associated adverse events., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target., Methods: First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade. Healthy tendon stromal cells were stimulated in vitro with IL-1β to assess the production of CCL20 by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of conditioned media from stimulated tenocytes in inducing T cell migration was interrogated using a Transwell system., Results: We observed an up-regulation of both CCR6 and CCL20 in the enthesis of IL-23 MC-treated mice, which was confirmed in human biopsy specimens. Specific targeting of the CCR6/CCL20 axis with a CCL20 locked dimer (CCL20LD) blocked entheseal inflammation, leading to profound reductions in clinical and proinflammatory markers in the joints and skin of IL-23 MC-treated mice. The stromal compartment in the tendon was the main source of CCL20 in this model and, accordingly, in vitro activated human tendon cells were able to produce this chemokine and to induce CCR6+ T cell migration, the latter of which could be blocked by CCL20LD., Conclusion: Our study highlights the pathogenic role of the CCR6/CCL20 axis in enthesitis and introduces the prospect of a novel therapeutic approach for treating patients with PsO and PsA., (© 2021, American College of Rheumatology.)

Introduction: Detection of atrial fibrillation (AF) is required to initiate oral anticoagulation (OAC) after cryptogenic stroke (CS). However, paroxysmal AF can be difficult to diagnose with short term cardiac monitoring. Taking an Australian payer perspective, we evaluated whether long-term continuous monitoring for 3 years with an insertable cardiac monitor (ICM) is cost-effective for preventing recurrent stroke in patients with CS., Methods: A lifetime Markov model was developed to simulate the follow-up of patients, comparing long-term continuous monitoring with an ICM to monitoring by conventional care. We used a linked evidence approach to estimate the rates of recurrent stroke when AF detection leads to initiation of OAC, as detected using ICM during the lifetime of the device or as detected using usual care. All diagnostic and patient management costs were modeled. Other model inputs were determined by literature review. Probabilistic sensitivity analysis (PSA) was undertaken to explore the effect of parameter uncertainty according to CHADS 2 score and OAC treatment effect., Results: In the base-case analysis, the model predicted an incremental cost-effectiveness ratio (ICER) of A$29 570 per quality-adjusted life year (QALY). Among CHADS 2 subgroups analyses, the ICER ranged from A$26 342/QALY (CHADS 2  = 6) to A$42 967/QALY (CHADS 2  = 2). PSA suggested that the probabilities of ICM strategy being cost-effective were 53.4% and 78.7%, at thresholds of $30 000 (highly cost-effective) and $50 000 per QALY (cost-effective), respectively., Conclusions: Long-term continuous monitoring with an ICM is a cost-effective intervention to prevent recurrent stroke in patients following CS in the Australian context., Competing Interests: Vincent Thijs has received modest speaker fees from Medtronic not connected with his work on this analysis; Klaus K. Witte has received modest consulting fees from Medtronic for his work on the economic analysis; this was work was based on but not with regards to this adaptation; Carmel Guarnieri, Koji Makino, and Dominic Tilden are employed by THEMA Consulting that received financial support from Medtronic Australasia to conduct the analysis and prepare the MSAC submission. Marianne Huynh is a Medtronic employee and stakeholder. John Gillespie was a Medtronic employee at the time of this analysis., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

In this work, we explore the applicability and limitations of the current third order density functional tight binding (DFTB3) formalism for treating transition metal ions using nickel as an example. To be consistent with recent parameterization of DFTB3 for copper, the parametrization for nickel is conducted in a spin-polarized formulation and with orbital-resolved Hubbard parameters and their charge derivatives. The performance of the current parameter set is evaluated based on structural and energetic properties of a set of nickel-containing compounds that involve biologically relevant ligands. Qualitatively similar to findings in previous studies of copper complexes, the DFTB3 results are more reliable for nickel complexes with neutral ligands than for charged ligands; nevertheless, encouraging agreement is noted in comparison to the reference method, B3LYP/aug-cc-pVTZ, especially for structural properties, including cases that exhibit Jahn-Teller distortions; the structures also compare favorably to available X-ray data in the Cambridge Crystallographic Database for a number of nickel-containing compounds. As to limitations, we find it is necessary to use different d shell Hubbard charge derivatives for Ni(I) and Ni(II), due to the distinct electronic configurations for the nickel ion in the respective complexes, and substantial errors are observed for ligand binding energies, especially for charged ligands, d orbital splitting energies and splitting between singlet and triplet spin states for Ni(II) compounds. These observations highlight that future improvement in intra-d correlation and ligand polarization is required to enable the application of the DFTB3 model to complex transition metal ions. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Alfaxalone is a neuroactive steroid derivative of pregnanedione that was recently reintroduced to the market for use as an induction agent in small animal anaesthesia. The aim of this study was to determine an intramuscular alfaxalone dose for safe immobilisation. Ten healthy New Zealand white rabbits were used to evaluate a single intramuscular injection of alfaxalone. The design of the study was a three-way, complete block, cross-over trial to compare the effect of alfaxalone at three doses (4, 6 and 8 mg). The mean duration of the effect for the 4, 6 and 8 mg/kg doses was, respectively, 36.9 (95% CI (31.6 to 42.3)), 51.8 (46.4 to 57.2) and 58.4 (52.8 to 63.9) minutes. The loss of the righting reflex was achieved after 3.1 (2.5 to 3.8), 2.4 (1.7 to 3.1) and 2.3 (1.6 to 2.9) minutes, respectively. The mean duration of the effect for the 6 and 8 mg doses was significantly higher than for the 4 mg dose (with estimated differences of 14.8 95% CI (8.8 to 20.8) minutes and 21.4 (15.3 to 27.6) minutes, respectively). No significant dose effect was observed before the loss of the righting reflex (P=0.14). Ear pinching and limb withdrawal were elicited in all groups at every dose. Doses of 4 or 6 mg/kg could be recommended; higher doses do not provide clinical benefits and can be associated with anaesthetic complication., (British Veterinary Association.)

The performance of a diagnostic test is best evaluated against a reference test that is without error. For many diseases, this is not possible, and an imperfect reference test must be used. However, diagnostic accuracy estimates may be biased if inaccurately verified status is used as the truth. Statistical models have been developed to handle this situation by treating disease as a latent variable. In this paper, we conduct a systematized review of statistical methods using latent class models for estimating test accuracy and disease prevalence in the absence of complete verification., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

The developing mouse tongue provides a model for discrete patterns of morphogenesis during short periods of embryonic development. Occipital somite-derived myogenic cells interact with cranial neural crest-derived ecto-mesenchymal cells to form the musculature of the tongue. The biochemical signals that control close range autocrine and/or paracrine signaling processes required to establish the fast-twitch complex tongue musculature are not known. The present study was designed to test the hypothesis that desmin, epidermal growth factor (EGF), and transforming growth factor-alpha (TGF alpha) and their cognate receptor, epidermal growth factor receptor (EGFr), are co-expressed during tongue myogenesis and define specific developmental stages of tongue muscle cell differentiation. To test this hypothesis, we performed studies to analyze the timing, position, and concentration of desmin, TGF alpha, EGF, and EGFr from embryonic day 9 (E9) through birth in Swiss Webster mouse tongue development. Desmin, TGF alpha, EGF, and EGFr co-localized to cells of myogenic lineage in the four occipital somites and subsequently in myoblasts and myotubes from E9 through E17. By newborn stage, desmin is localized to discrete regions in myofibers corresponding to Z-line delimiting sarcomeres, and A-band within sarcomeres; immunostaining for desmin, TGF alpha, and EGF persisted in differentiated myotubes and striated skeletal muscle. Desmin increased from 0.01% at E11 to 0.51% of the total protein by E17 and at birth. Concomitantly, the patterns and increases in TGF alpha, EGF, and EGFr showed significant increases during the same developmental period. The temporal and positional co-localization of TGF alpha, EGF, and EGFr support the hypothesis that autocrine and paracrine regulation of desmin by actions of growth factor ligand and receptor defines critical stages of tongue myogenesis.