Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome.

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

Reverse Shoulder Arthroplasty to Treat Proximal Humerus Fracture Sequelae: A Review.

While several proximal humerus fractures treated nonsurgically reach satisfactory outcomes, some become symptomatic malunions or nonunions with pain and dysfunction. When joint-preserving options such as malunion or nonunion repair are not optimal because of poor remaining bone stock or glenohumeral arthritis, shoulder arthroplasty is a good option. Because of the semiconstrained design of reverse shoulder arthroplasty, it is effective at improving function when there is notable bony deformity or a torn rotator cuff. Clinical studies have demonstrated reliable outcomes, and a classification system exists that is helpful for predicting prognosis and complications. By understanding the associated pearls and pitfalls and with careful management of the tuberosities, reverse shoulder arthroplasty is a powerful tool for managing proximal humerus fracture sequelae.

Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways. We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy. METHODS: The TORREY trial was a phase 2, randomised, multicentre, multinational, double-blind, placebo-controlled study. Patients with PAH from 40 hospital and community sites were randomly assigned 1:1 via interactive response technologies to receive seralutinib (60 mg twice daily for 2 weeks, then increased to 90 mg twice daily as tolerated) or placebo by dry powder inhaler twice daily for 24 weeks. Randomisation was stratified by baseline pulmonary vascular resistance (PVR; <800 dyne·s/cm5 and ≥800 dyne·s/cm5). Patients were eligible if classified as WHO Group 1 PH (PAH), WHO Functional Class II or III, with a PVR of 400 dyne·s/cm5 or more, and a 6 min walk distance of between 150 m and 550 m. The primary endpoint was change in PVR from baseline to 24 weeks. Analyses for efficacy endpoints were conducted in randomly assigned patients (intention-to-treat population). Safety analyses included all patients who received the study drug. TORREY was registered with ClinicalTrials.gov (NCT04456998) and EudraCT (2019-002669-37) and is completed. FINDINGS: From Nov 12, 2020, to April 20, 2022, 151 patients were screened for eligibility, and following exclusions, 86 adults receiving PAH background therapy were randomly assigned to seralutinib (n=44; four male, 40 female) or placebo (n=42; four male, 38 female), and comprised the intention-to-treat population. At baseline, treatment groups were balanced except for a higher representation of WHO Functional Class II patients in the seralutinib group. The least squares mean change from baseline to week 24 in PVR was 21·2 dyne·s/cm5 (95% CI -37·4 to 79·8) for the placebo group and -74·9 dyne·s/cm5 (-139·7 to -10·2) for the seralutinib group. The least squares mean difference between the seralutinib and placebo groups for change in PVR was -96·1 dyne·s/cm5 (95% CI -183·5 to -8·8; p=0·03). The most common treatment-emergent adverse event in both treatment groups was cough: 16 (38%) of 42 patients in the placebo group; 19 (43%) of 44 patients in the seralutinib group. INTERPRETATION: Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH. FUNDING: Gossamer Bio.

Cystine/glutamate antiporter xCT controls skeletal muscle glutathione redox, bioenergetics and differentiation.

Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to cysteine. As glutathione redox is important in muscle regeneration in aging, we hypothesized that xCT exerts upstream control over skeletal muscle glutathione redox, metabolism and regeneration. Bioinformatic analyses of publicly available datasets revealed that expression levels of xCT and GSH-related genes are inversely correlated with myogenic differentiation genes. Muscle satellite cells (MuSCs) isolated from Slc7a11sut/sut mice, which harbour a mutation in the Slc7a11 gene encoding xCT, required media supplementation with 2-mercaptoethanol to support cell proliferation but not myotube differentiation, despite persistently lower GSH. Slc7a11sut/sut primary myotubes were larger compared to WT myotubes, and also exhibited higher glucose uptake and cellular oxidative capacities. Immunostaining of myogenic markers (Pax7, MyoD, and myogenin) in cardiotoxin-damaged tibialis anterior muscle fibres revealed greater MuSC activation and commitment to differentiation in Slc7a11sut/sut muscle compared to WT mice, culminating in larger myofiber cross-sectional areas at 21 days post-injury. Slc7a11sut/sut mice subjected to a 5-week exercise training protocol demonstrated enhanced insulin tolerance compared to WT mice, but blunted muscle mitochondrial biogenesis and respiration in response to exercise training. Our results demonstrate that the absence of xCT inhibits cell proliferation but promotes myotube differentiation by regulating cellular metabolism and glutathione redox. Altogether, these results support the notion that myogenesis is a redox-regulated process and may help inform novel therapeutic approaches for muscle wasting and dysfunction in aging and disease.

Metabolic network analysis of pre-ASD newborns and 5-year-old children with autism spectrum disorder.

Classical metabolomic and new metabolic network methods were used to study the developmental features of autism spectrum disorder (ASD) in newborns (n = 205) and 5-year-old children (n = 53). Eighty percent of the metabolic impact in ASD was caused by 14 shared biochemical pathways that led to decreased anti-inflammatory and antioxidant defenses, and to increased physiologic stress molecules like lactate, glycerol, cholesterol, and ceramides. CIRCOS plots and a new metabolic network parameter, V ° net, revealed differences in both the kind and degree of network connectivity. Of 50 biochemical pathways and 450 polar and lipid metabolites examined, the developmental regulation of the purine network was most changed. Purine network hub analysis revealed a 17-fold reversal in typically developing children. This purine network reversal did not occur in ASD. These results revealed previously unknown metabolic phenotypes, identified new developmental states of the metabolic correlation network, and underscored the role of mitochondrial functional changes, purine metabolism, and purinergic signaling in autism spectrum disorder.

Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study.

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

A Retrospective Review and Comprehensive Tumour Profiling of Advanced Non-Melanomatous Cutaneous Spindle Cell Neoplasms Treated with Immune-Checkpoint Inhibitors.

Non-melanomatous cutaneous spindle cell neoplasms are a rare group of malignancies that present a diagnostic challenge, and for which there is a lack of consensus on how to best manage patients with advanced disease and only limited reports of immune-checkpoint inhibitor (ICI) responses. In this study, we performed a single-center retrospective review of treatment outcomes for all advanced non-melanomatous cutaneous spindle cell neoplasms treated with ICIs. Blinded histopathology reviews occurred to confirm each diagnosis. Comprehensive tumour profiling included whole exome sequencing for tumour mutational burden (TMB) and ultraviolet(UV) signatures, and immunohistochemistry for immune-cell infiltration (CD4/CD3/CD8/CD103/CD20) and immune-checkpoint expression (PD-L1/LAG3/TIGIT). Seven patients were identified. The objective response rate was 86% (6/7) with five complete responses (CR). Responses were durable with two patients in CR > 30 months after ICI commencement. All patients had high TMB and UV signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression. In advanced non-melanomatous cutaneous spindle cell neoplasms, excellent responses to ICIs with durable disease control were observed. ICIs are worthy of further exploration in these patients. UV signatures and high TMB could be used to help select patients for treatment.

Global trends in carbapenem- and difficult-to-treat-resistance among World Health Organization priority bacterial pathogens: ATLAS surveillance program 2018-2022.

OBJECTIVES: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022. METHODS: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. ß-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates. RESULTS: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions. CONCLUSION: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship.

Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4+ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1fl/flMaffl/flCd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Cre and Maffl/flCd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell-myeloid-neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease.

Needles in haystacks: monitoring the potential escape of bioaerosolised antibacterial resistance genes from wastewater treatment plants with air and phyllosphere sampling.

Wastewater treatment plants are well-known point sources of emissions of antibacterial resistance genes (ARGs) into the environment. Although most work to date has focused on ARG dispersal via effluent, aerial dispersal in bioaerosols is a poorly understood, but likely important vector for ARG dispersal. Recent evidence suggests that ARG profiles of the conifer needle phyllosphere could be used to measure bioaerosol dispersal from anthropogenic sources. Here, we assessed airborne dispersal of ARGs from wastewater treatment plants in Wales, UK and Quebec, Canada, using conifer needles as passive bioaerosol monitors. ARG profiles of wastewater were compared to those of conifer phyllosphere using high-throughput qPCR. ARG richness was significantly lower in conifer phyllosphere samples than wastewater samples, though no differences were observed across the dispersal gradients. Mean copy number of ARGs followed a similar trend. ARG profiles showed limited, but consistent patterns with increasing distance from wastewater treatment plants, but these did not align with those of wastewater samples. For example, proportional abundance of aminoglycosides decreased over the dispersal gradient in Wales, whereas mobile genetic elements showed the inverse relationship. In summary, while distinct ARG profiles exist along dispersal gradients, links to those of wastewater were not apparent.

Antimicrobial stewardship markers and healthcare-associated pneumonia threshold criteria in UK hospitals: analysis of the MicroGuideTm application.

Background: To address antimicrobial resistance, antimicrobial stewardship (AMS) principles must be implemented and adhered to. Clinical decision aids such as the MicroGuideTM app are an important part of these efforts. We sought to evaluate the consistency of core AMS information and the diversity of classification thresholds for healthcare-associated pneumonia (HAP) in the MicroGuide app. Methods: Guidelines in the MicroGuide app were extracted and analysed for content related to AMS and HAP. Guidelines were characterized according to HAP naming classification; community-acquired pneumonia (CAP) classifications were analysed to serve as a comparator group. Results: In total, 115 trusts (119 hospitals) were included. Nearly all hospitals had developed MicroGuide sections on AMS (n = 112/119, 94%) and sepsis management (n = 117/119, 98%). Other AMS sections were outpatient parenteral antimicrobial therapy (47%), antifungal stewardship (70%), critical care (23%) and IV to oral switch therapy (83%). Only 9% of hospitals included guidance on the maximum six key AMS sections identified. HAP definitions varied widely across hospitals with some classifying by time to onset and some classifying by severity or complexity. The largest proportion of HAP guidelines based classification on severity/complexity (n = 69/119, 58%). By contrast, definitions in CAP guidelines were uniform. Conclusions: The high heterogeneity in HAP classification identified suggests inconsistency of practice in identifying thresholds for HAP in the UK. This complicates HAP management and AMS practices. To address HAP in alignment with AMS principles, a comprehensive strategy that prioritizes uniform clinical definitions and thresholds should be developed.

Magnetostriction measurements at milli-kelvin temperatures using a Fabry-Pérot interferometer.

This paper demonstrates an optical technique to measure magnetostrictive strain in a cryogenic environment using a Fabry-Pérot resonator spaced by crystal samples. Optical measurement techniques are calibration-free and highly sensitive. This technique was used to measure the magnetostrictive strain of neodymium gallate at a temperature of 49 mK to be λ = 1.3 × 10-5 at 3 T, with a sensitivity of 3.0 × 10-8. We highlight the interesting properties of the crystal's magnetic ordering. The sensitivity of this technique was limited by the wavemeter used to measure the laser frequency, and significant improvements in the sensitivity should be possible.

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Assessment of perineural spread in advanced cutaneous squamous cell carcinomas treated with immunotherapy.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system. METHODS: This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). RESULTS: Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT. CONCLUSIONS: PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.

Scar massage as an intervention for post-surgical scars: A practice survey of Australian hand therapists.

Introduction: Scar massage is a commonly used treatment in hand therapy. The current empirical evidence that supports it is disparate and of variable quality, with no established effective dosage and method proposed. This study aimed to identify the current practice among Australian hand therapists using massage as an intervention for scarring following surgery to the hand and upper limb. Methods: A purposely designed self-report online survey was emailed to current members of the Australian Hand Therapy Association (n = 958). Data collected included demographics, intervention techniques, conditions treated and protocols, scar assessment and knowledge and training about scar massage as a clinical intervention. Results: A total of 116 completed questionnaires were received (a response rate of 12.1%). All respondents used scar massage as part of their clinical practice with 98% to improve soft tissue glide (n = 114), 92% for hypersensitivity (n = 107), and 84% to increase hand function (n = 97). Only 18% (n = 21) of respondents used standardised outcome measures, and most therapists had learned scar massage from a colleague (81%). Conclusions: Commonalities in how respondents implemented scar massage were found. Participants reported relying primarily on clinical experience to inform their practice. Whilst scar massage was widely used, few respondents had received formal skills training or completed outcome measures regularly to formally evaluate its clinical efficacy or impact. Replication of this study with a larger international sample of participants is warranted to determine if these findings reflect general practice.

Real-World Experience of Immune-Checkpoint Inhibitors in Older Patients with Advanced Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Older patients are often underrepresented in clinical trials owing to exclusionary comorbidities, which are more common with age. Chemotherapy is poorly tolerated in older comorbid advanced cutaneous squamous cell carcinoma (CSCC) patients; however, little is known on the efficacy and tolerability of immune-checkpoint inhibitors (ICIs) in this population. To our knowledge, this is the largest dedicated report on a cohort of older patients with advanced CSCC treated with immunotherapy to date. OBJECTIVE: The aim was to report outcomes of ICI use in a real-world older cohort with advanced CSCC. PATIENTS AND METHODS: A single-centre retrospective audit of all patients treated via an access scheme providing ICIs to patients with advanced CSCC was conducted. Participants were ≥ 70 years of age and had advanced CSCC not amenable to curative surgery or radiotherapy. Best overall response rate (ORR), 12-month overall survival (OS) and progression-free survival (PFS), and toxicity rates were assessed. RESULTS: A total of 53 patients were analysed. The median age was 81.8 years (range 70.1-96.8); 81% were male; 34% were immunocompromised; and 34% had an Eastern Cooperative Oncology Group (ECOG) performance status score of ≥ 2. The ORR was 57%, and 12-month OS and PFS were 63% (95% confidence interval [CI] 44-78) and 41% (95% CI 25-57), respectively. Thirty-two per cent developed an immune-related adverse event (irAE), but only two patients experienced a grade 3 irAE, with no treatment-related deaths. Higher ECOG score was associated with worse OS and PFS. No significant association was identified for increasing age, sex, Charlson Comorbidity Index score, or immunocompromised status. CONCLUSIONS: ICIs have demonstrated efficacy and have an acceptable safety profile among older patients with advanced CSCC, with comparable efficacy to what has been demonstrated in current clinical trials.

Heme metabolism in nonerythroid cells.

Heme is an iron-containing prosthetic group necessary for the function of several proteins termed "hemoproteins." Erythrocytes contain most of the body's heme in the form of hemoglobin and contain high concentrations of free heme. In nonerythroid cells, where cytosolic heme concentrations are 2 to 3 orders of magnitude lower, heme plays an essential and often overlooked role in a variety of cellular processes. Indeed, hemoproteins are found in almost every subcellular compartment and are integral in cellular operations such as oxidative phosphorylation, amino acid metabolism, xenobiotic metabolism, and transcriptional regulation. Growing evidence reveals the participation of heme in dynamic processes such as circadian rhythms, NO signaling, and the modulation of enzyme activity. This dynamic view of heme biology uncovers exciting possibilities as to how hemoproteins may participate in a range of physiologic systems. Here, we discuss how heme is regulated at the level of its synthesis, availability, redox state, transport, and degradation and highlight the implications for cellular function and whole organism physiology.

Comparison of the out-of-pocket costs of Medicare-funded telepsychiatry and face-to-face consultations: A descriptive study.

OBJECTIVE: Telepsychiatry items in the Australian Medicare Benefits Schedule (MBS) were expanded following the COVID-19 pandemic. However, their out-of-pocket costs have not been examined. We describe and compare patient out-of-pocket payments for face-to-face and telepsychiatry (videoconferencing and telephone) MBS items for outpatient psychiatric services to understand the differential out-of-pocket cost burden for patients across these modalities. METHODS: out-of-pocket cost information was obtained from the Medical Costs Finder website, which extracted data from Services Australia's Medicare claims data in 2021-2022. Cost information for corresponding face-to-face, video, and telephone MBS items for outpatient psychiatric services was compared, including (1) Median specialist fees; (2) Median out-of-pocket payments; (3) Medicare reimbursement amounts; and (4) Proportions of patients subject to out-of-pocket fees. RESULTS: Medicare reimbursements are identical for all comparable face-to-face and telepsychiatry items. Specialist fees for comparable items varied across face-to-face to telehealth options, with resulting differences in out-of-pocket costs. For video items, higher proportions of patients were not bulk-billed, with greater out-of-pocket costs than face-to-face items. However, the opposite was true for telephone items compared with face-to-face items. CONCLUSIONS: Initial cost analyses of MBS telepsychiatry items indicate that telephone consultations incur the lowest out-of-pocket costs, followed by face-to-face and video consultations.