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HIV-associated neurocognitive disorder (HAND) remains prevalent despite antiretroviral therapy and involves white matter damage in the brain. Although iron is essential for myelination and myelin maintenance/repair, its role in HAND is largely unexplored. We tested the hypotheses that cerebrospinal fluid (CSF) heavy-chain ferritin (Fth1) and transferrin, proteins integral to iron delivery and myelination, are associated with neurocognitive performance in people with HIV (PWH). Fth1, transferrin, and the pro-inflammatory cytokines TNF-α and IL-6 were quantified in CSF at baseline (entry) in 403 PWH from a prospective observational study who underwent serial, comprehensive neurocognitive assessments. Associations of Fth1 and transferrin with Global Deficit Score (GDS)-defined neurocognitive performance at baseline and 30-42 months of follow-up were evaluated by multivariable regression. While not associated with neurocognitive performance at baseline, higher baseline CSF Fth1 predicted significantly better neurocognitive performance over 30 months in all PWH (p < 0.05), in PWH aged < 50 at 30, 36, and 42 months (all p < 0.05), and in virally suppressed PWH at all three visit time-points (all p < 0.01). Higher CSF transferrin was associated with superior neurocognitive performance at all visits, primarily in viremic individuals (all p < 0.05). All associations persisted after adjustment for neuro-inflammation. In summary, higher CSF Fth1 is neuroprotective over prolonged follow-up in all and virally suppressed PWH, while higher CSF transferrin may be most neuroprotective during viremia. We speculate that higher CSF levels of these critical iron-delivery proteins support improved myelination and consequently, neurocognitive performance in PWH, providing a rationale for investigating their role in interventions to prevent and/or treat HAND.

Eating disorders (EDs) have detrimental effects on an individual’s physical and mental health, along with significant interpersonal, social and economic effects. Furthermore, men who are suffering with an ED face unique challenges with this. Men suffering with EDs have historically received little attention within ED research, diagnosis and intervention. However, the number of men suffering with these issues is significant and growing. Understanding of EDs tend to ignore male experiences, meaning many are left to suffer in silence until the ED has developed to a critical point. However, many now recognize the need to understand the issues facing men suffering with an ED. By improving our understanding, we can better improve early detection, diagnosis and treatment for those who are suffering. This paper aims to provide a comprehensive general introduction to this growing area of research and it is hoped that it will be of good use to interested researchers, students and the general public. Prevalence, presentation, history, diagnosis and more will be covered in order to provide a well-rounded understanding of EDs in men.

Background: Systematic reviews, such as those prepared by Cochrane, are the strongest evidence on which to base recommendations in clinical guidelines. Network meta-analysis (NMA) can be used to combine the results of studies to compare multiple treatments, which is advantageous over pair-wise meta-analysis (PW-MA) that compares two treatments. We aimed to summarise which, when, where, who, and why Cochrane Reviews that applied NMA were cited in guidelines; and to compare the citation of NMA reviews in guidelines with PW-MA reviews. Methods and findings: We carried out a systematic review of Cochrane reviews that applied NMA and we summarised their citation in guidelines. The Cochrane Database of Systematic Reviews was searched (15th January 2024). Additionally, a cohort of Cochrane reviews that applied PW-MA was matched to the NMA reviews. Two authors assessed eligibility and extracted data. We summarised review and guideline characteristics, and the use of the review in guidelines. Results: Of the 60 included NMA reviews, 26 reviews (43%) were cited in 89 guidelines (1–13 per review). 15 NMA reviews (58%) were first cited within two years of publication, with the remaining 11 reviews (42%) cited 2–6 years later. 52 guideline developers authored the guidelines. The number of citations was higher for NMA than PW-MA reviews (rate ratio 1.53 (1.08 to 2.19), p = 0.02). The number of times reviews were commissioned or cited alongside a recommendation was also higher for NMA than PW-MA reviews (rate ratio 4.40 (1.80 to 13.14), p = 0.003). NMA reviews were more likely to be cited in the text surrounding a recommendation or used for NICE guideline development (1.94 (1.08 to 3.63), p = 0.03). Conclusions: Cochrane NMA reviews appear to have more impact than PW-MA reviews, but many are not cited in guidelines. Further work is needed to explore the barriers to use of NMAs and promote their use. [ABSTRACT FROM AUTHOR]

The Australian government has recently established a Royal Commission on Defence and Veteran Suicide (DVSRC). Veteran suicide rates for those who have left the Australian Defence Force (ADF) are higher than the national average and there has been little success in reducing this over an extended period of time. Veteran suicide is poorly understood, and the collected data is imprecise and incomplete. Deployment trauma and Post-traumatic stress disorder (PTSD i.e. a mental health lens) are taken for granted as the principal causes. This article presents a case study on institutional abuse in the ADF which led to the veteran attempting suicide on numerous occasions. The article draws upon the mental health and moral injury knowledge but questions their centrality and dominance. Military Institutional Abuse (MIA) and its consequent identity wounds are explained as institutional causes of military trauma. We argue that these institutional abuse processes and their consequences, occurring within military moral geographies, lead to suicidal ideation and attempt. These are situated within wider relations of civil society, the state, and the military. [ABSTRACT FROM AUTHOR]

Integrity is an ongoing concern in the public sector. Contemporary examples include fraud incidents, ethical violations, theft, and a disregard of legal advice resulting in significant harms to the public. Public service integrity management systems are interconnected frameworks of legislation and institutions intended to reduce such incidents, including Codes of Conduct (CoCs). A CoC is typically defined as a written set of norms that outline virtuous or desired behaviours, often creating or linking to sanctions for violations. Despite matters of integrity and corruption being a high concern for citizens, no method exists to compare monitoring, reporting, and review of CoCs across jurisdictions. We developed and applied a method to assess CoC implementation using specific assessment criteria developed by reviewing available content across jurisdictions and the current literature on CoCs and integrity management. Our results reveal substantial inconsistency between jurisdictions and a lack of available or accessible data for many CoC elements. Our method serves both as a tool for analysis of the effectiveness of CoCs over time and as an assessment of how jurisdictions are currently reporting on their compliance with their own CoCs. Points for practitioners: A lack of evidence exists in terms of how CoCs are monitored, reported on, and reviewed.As a first stage of a research program, we develop and apply a method to all Australian states, territories, and the Australian Public Service to compare the monitoring, reporting, and review activities undertaken by these jurisdictions.Application of the method reveals opportunities for jurisdictions to improve the availability and accessibility of CoC data collection, reporting, and review.Auditors General and Public Accounts Committees should consider this method as part of their works programs and potentially use it to inform their scrutiny programs and requirements for performance and annual reporting.Public Service Commissions could find the data useful in adapting and improving their CoC monitoring, reporting, and review systems. [ABSTRACT FROM AUTHOR]

BackgroundHIV-associated neurocognitive disorder (HAND) remains common, despite antiretroviral therapy (ART). HIV dysregulates iron metabolism, but cerebrospinal fluid (CSF) levels of iron and iron-transport proteins in HIV-infected (HIV+) persons are largely unknown. The objectives of this study were to characterize CSF iron-related biomarkers in HIV+ adults and explore their relationships to known predictors of HAND.MethodsWe quantified total iron, transferrin and heavy-chain (H)-ferritin by immunoassay in CSF sampled by lumbar puncture in 403 HIV+ participants in a multi-center, observational study and evaluated biomarker associations with demographic and HIV-related correlates of HAND [e.g., age, sex, self-reported race/ethnicity, ART, and detectable plasma virus and CSF viral load (VL)] by multivariable regression. In a subset (N = 110) with existing CSF: serum albumin (QAlb) measurements, QAlb and comorbidity severity were also included as covariates to account for variability in the blood-CSF-barrier.ResultsAmong 403 individuals (median age 43 years, 19% women, 56% non-Whites, median nadir CD4+ T cell count 180 cells/µL, 46% with undetectable plasma virus), men had 25% higher CSF transferrin (median 18.1 vs. 14.5 µg/mL), and 71% higher H-ferritin (median 2.9 vs. 1.7 ng/mL) than women (both p-values ≤0.01). CSF iron was 41% higher in self-reported Hispanics and 27% higher in (non-Hispanic) Whites than in (non-Hispanic) Blacks (median 5.2 and 4.7 µg/dL in Hispanics and Whites, respectively, vs. 3.7 µg/dL in Blacks, both p ≤ 0.01); these findings persisted after adjustment for age, sex, and HIV-specific factors. Median H-ferritin was 25% higher (p  50 years) than in younger persons (age ≤ 35 years; both p

BackgroundMitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.MethodsWe quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS

The role of iron dyshomeostasis in neurodegenerative disease has implicated the involvement of genes that regulate brain iron. The homeostatic iron regulatory gene (HFE) has been at the forefront of these studies given the role of the H63D variant (H67D in mice) in increasing brain iron load. Despite iron's role in oxidative stress production, H67D mice have shown robust protection against neurotoxins and improved recovery from intracerebral hemorrhage. Previous data support the notion that H67D mice adapt to the increased brain iron concentrations and hence develop a neuroprotective environment. This adaptation is particularly evident in the lumbar spinal cord (LSC) and ventral midbrain (VM), both relevant to neurodegeneration. We studied C57BL6/129 mice with homozygous H67D compared to WT HFE. Immunohistochemistry was used to analyze dopaminergic (in the VM) and motor (in the LSC) neuron population maturation in the first 3 months. Immunoblotting was used to measure protein carbonyl content and the expression of oxidative phosphorylation complexes. Seahorse assay was used to analyze metabolism of mitochondria isolated from the LSC and VM. Finally, a Nanostring transcriptomic analysis of genes relevant to neurodegeneration within these regions was performed. Compared to WT mice, we found no difference in the viability of motor neurons in the LSC, but the dopaminergic neurons in H67D mice experienced significant decline before 3 months of age. Both regions in H67D mice had alterations in oxidative phosphorylation complex expression indicative of stress adaptation. Mitochondria from both regions of H67D mice demonstrated metabolic differences compared to WT. Transcriptional differences in these regions of H67D mice were related to cell structure and adhesion as well as cell signaling. Overall, we found that the LSC and VM undergo significant and distinct metabolic and transcriptional changes in adaptation to iron‐related stress induced by the H67D HFE gene variant. [ABSTRACT FROM AUTHOR]

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes. [ABSTRACT FROM AUTHOR]

Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron's ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated. Some claim that mutated HFE exacerbates oxidative stress and neuroinflammation, thus predisposing carriers to neurodegeneration-linked pathologies. However, H63D HFE has also been shown to slow the progression of multiple neurodegenerative diseases and to protect against environmental toxins that cause neurodegeneration. These conflicting results showcase the need to further understand the contribution of HFE variants to neurodegenerative disease heterogeneity. Data from mouse models consistently demonstrate robust neuroprotection against toxins known to increase the risk of neurodegenerative disease. This may represent an adaptive, or hormetic, response to increased iron, which leaves cells better protected against future stressors. This review describes the current research regarding the contribution of HFE variants to neurodegenerative disease prognosis in the context of a hormetic model. To our knowledge, this is the first time that a hormetic model for neurodegenerative disease has been presented. [ABSTRACT FROM AUTHOR]

Summary: Iron deficiency (ID) and iron‐deficiency anaemia (IDA) are global public health concerns, most commonly afflicting children, pregnant women and women of childbearing age. Pathological outcomes of ID include delayed cognitive development in children, adverse pregnancy outcomes and decreased work capacity in adults. IDA is usually treated by oral iron supplementation, typically using iron salts (e.g. FeSO4); however, dosing at several‐fold above the RDA may be required due to less efficient absorption. Excess enteral iron causes adverse gastrointestinal side effects, thus reducing compliance, and negatively impacts the gut microbiome. Recent research has sought to identify new iron formulations with better absorption so that lower effective dosing can be utilized. This article outlines emerging research on oral iron supplementation and focuses on molecular mechanisms by which different supplemental forms of iron are transported across the intestinal epithelium and whether these transport pathways are subject to regulation by the iron‐regulatory hormone hepcidin. [ABSTRACT FROM AUTHOR]