Optimizing Older Adult Mental Health in Support of Healthy Ageing: A Pluralistic Framework to Inform Transformative Change across Community and Healthcare Domains.

This paper describes a pluralistic framework to inform transformative change across community and healthcare domains to optimize the mental health of older adults in support of healthy ageing. An extensive review and analysis of the literature informed the creation of a framework that contextualizes the priority areas of the WHO Decade of Health Ageing (ageism, age-friendly environments, long-term care, and integrated care) with respect to older adult mental health. The framework additionally identifies barriers, facilitators, and strategies for action at macro (social/system), meso (services/supports), and micro (older adults) levels of influence. This conceptual (analytical) framework is intended as a tool to inform planning and decision-making across policy, practice, education and training, research, and knowledge mobilization arenas. The framework described in this paper can be used by countries around the globe to build evidence, set priorities, and scale up promising practices (both nationally and sub-nationally) to optimize the mental health and healthy ageing trajectories of older adults as a population.

Child Sexual Abuse in Nigeria: A Systematic Review.

Child sexual abuse (CSA) is a major social and public health issue that creates short- and long-lasting impacts on victims, families, and society. While global researchers have considered the topic of CSA since the 19th century, the Nigerian context has been largely ignored. Yet, without sufficient evidence and understanding, making changes to practices and policies becomes almost impossible. The review aimed to gain insights into the nature and extent of CSA and identify areas for improvement in practice and research in Nigeria. This article presents the findings of a systematic review of 31 empirical articles related to CSA in Nigeria. Using key search terms along Boolean operators and truncation, PubMed, PsycINFO, CINAHL, ASSIA, PILOTS, African Journals Online, and Google Scholar were searched. A total of 1,325 studies were found, and 31 empirical studies, including 20 quantitative, 9 qualitative, and 2 mixed methods studies, were included. The review findings reveal the discourse on CSA and delve into various aspects such as its prevalence, manifestation patterns, root causes, management, and consequential impact on victims and societal domains. The gaps in the existing literature are identified and explored to identify areas for improvement in victim services, societal awareness, and healthcare practices and relevant policies. The sociocultural norms not only heightened children's vulnerability to sexual abuse but also posed significant barriers to them disclosing such abuse. Survivors of CSA often receive inadequate care, indicating a pressing need for improvements in this area. Implications for research, policy, and conclusion were discussed.

Comparison of noninvasive prenatal screening with combined first-trimester screening as a frontline screening approach for common trisomies in a public hospital in Australia.

BACKGROUND: Combined first-trimester screening (cFTS) for fetal anomalies involves maternal serum screening for biochemical markers and measurement of the nuchal translucency (NT) by ultrasound. Noninvasive prenatal screening (NIPS) analyses cell-free DNA present in a maternal blood sample for presence of fetal chromosomal aneuploidies. AIMS: To compare NIPS with cFTS as frontline screening in a public hospital in Australia. MATERIALS AND METHODS: Women were offered NIPS in addition to the usual cFTS routinely offered to all women at a public hospital in NSW, Australia. The cFTS sample was collected at ten weeks' gestation and the NIPS sample at 12 weeks' gestation at the ultrasound appointment. RESULTS: In a low-risk population of 997 women, frontline NIPS had a screen-positive rate of 0.5% (5/997) vs 4.2% (42/997) with cFTS. cFTS correctly identified one trisomy 21 case and one trisomy 18 case; however, there were two trisomy 18 false negatives. Of five positive NIPS calls, four were correctly identified as trisomy 21 (one) and trisomy 18 (three); there were no NIPS false negatives. Overall, the false-positive rate with NIPS was 0.1% vs 4.0% by cFTS. CONCLUSIONS: The lower screen-positive rate with NIPS for common trisomies was a result of the significantly lower false-positive rate with NIPS. Consequently, NIPS as first-line screening, even if funded by the hospital, may provide cost savings. We believe NIPS should be used from ten weeks' gestation in conjunction with morphology ultrasound for routine first-trimester prenatal management.

The experience of structural burden for culturally and linguistically diverse family carers of people living with dementia in Australia.

Evidence suggests that family carers of culturally and linguistically diverse (CALD) people living with dementia experience higher stress and unmet need than the general Australian population. These disparities are often framed as the result of CALD communities failing to seek formal support. Challenging this, we draw on the concept of 'structural burden' to explore how the complexity of health and aged systems contribute to the burden that CALD carers experience. We conducted semi-structured interviews with 104 family carers for CALD people with dementia in Australia, followed by thematic analysis of transcripts. Additional to structural burdens encountered by the general older population, CALD carers faced challenges understanding Australia's Anglo-centric aged care system, locating culturally appropriate care and were required to translate the languages and operations of health and aged care systems into terms their family members understood. This burden was mitigated by the presence of ethno-specific organisations and other navigation support. Australia's aged care system has moved towards centralised governance and consumer-directed care provision. This system involves a confusing array of different programmes and levels, bureaucratic applications and long waiting times. Carers' encounters with these systems demonstrates how some CALD people are being left behind by the current aged care system. While ethno-specific services can reduce this burden, not all CALD groups are represented. Consequently, improving access to dementia care among CALD populations requires entry point and navigation support that is culturally appropriate and linguistically accessible.

Effectiveness of alternative prenatal genetic counselling methods in a cohort of pregnant women from a low socio-economic population.

BACKGROUND: There are concerns about the capacity of healthcare providers to adequately counsel women on the implications of noninvasive prenatal screening (NIPS). Studies suggest that more resource-efficient counselling methods are needed for broad adoption. AIMS: We prospectively examined the effectiveness of alternative methods of prenatal counselling on a patient's knowledge and understanding of prenatal testing choices, with a focus on NIPS. We also evaluated prenatal test choice and emotional well-being after making this decision. METHODS: Women from a low socio-economic population were offered NIPS at no additional cost along with typical prenatal screening and diagnosis. Study participants underwent prenatal counselling via a web-based video consultation or a telephone consultation with a genetic counsellor. Participants were asked to complete pre-counselling and post-counselling questionnaires. RESULTS: Of 1000 women enrolled, 600 completed both surveys in full and were included in the analysis. Of these, 354 (59%) underwent counselling via a telephone consultation and 246 (41%) via the web-based video consultation. Both counselling methods led to a significant increase in patient knowledge (P < 0.01). NIPS uptake was equivalent between groups. Patients expressed a high level (90%) of satisfaction with their prenatal screen choice, with no significant difference (P > 0.10) between telephone and web participants. CONCLUSIONS: Alternative methods of counselling such as a web-based education portal can be highly effective and should be considered to enable informed decision-making prior to undergoing prenatal screening such as NIPS. Further, web-based education tools could be beneficial for those in rural areas with limited access to healthcare providers and non-native speakers.

Boundary Crossers: How Providers Facilitate Ethnic Minority Families' Access to Dementia Services.

OBJECTIVES: Providers who work closely with ethnic minority people with dementia and their families are pivotal in helping them access services. However, few studies have examined how these providers actually do this work. Using the concept of "boundary crossers," this article investigates the strategies applied by these providers to facilitate access to dementia services for ethnic minority people with dementia and their families. METHODS: Between 2017 and 2020, in-depth video-recorded interviews were conducted with 27 health, aged care, and community service providers working with ethnic minority people living with dementia across Australia. Interviews were conducted in one of seven languages and/or in English, then translated and transcribed verbatim into English. The data were analyzed thematically. RESULTS: Family and community stigma associated with dementia and extra-familial care were significant barriers to families engaging with services. To overcome these barriers, participants worked at the boundaries of culture and dementia, community and systems, strategically using English and other vernaculars, clinical and cultural terminology, building trust and rapport, and assisting with service navigation to improve access. Concurrently, they were cognizant of familial boundaries and were careful to provide services that were culturally appropriate without supplanting the families' role. DISCUSSION: In negotiating cultural, social, and professional boundaries, providers undertake multidimensional and complex work that involves education, advocacy, negotiation, navigation, creativity, and emotional engagement. This work is largely undervalued but offers a model of care that facilitates social and community development as well as service integration across health, aged care, and social services.

The use of the ketogenic diet in the treatment of psychiatric disorders.

INTRODUCTION: The ketogenic diet (KD) is a high-fat, low-carbohydrate, and moderate-protein diet that has shown benefit as a treatment in neurologic disorders and may serve as a therapeutic option in individuals with psychiatric disorders. METHODS: A search was conducted using EBSCOhost and PubMed databases for studies relating to ketogenic or low-carbohydrate diets and psychiatric disorders. RESULTS: A total of 32 experimental or observational studies were identified by initial search strategies, 14 of which met the criteria to be included in this analysis. Although specific diet formulations varied somewhat between studies, they all generally examined low-carbohydrate dietary intake with the goal of producing a ketotic state. The studies included in this review indicated the KD was beneficial in reducing symptoms associated with various psychiatric disorders. DISCUSSION: This review summarizes the available evidence regarding the efficacy of the ketogenic diet in psychiatric disease states. Data from the studies analyzed demonstrated a positive response in individuals who were able to remain on the diet, regardless of the disease state. However, there is a need for more data to clearly define the specific benefits the KD may provide.

Beyond crisis: Enacted sense-making among ethnic minority carers of people with dementia in Australia.

The 'family crisis' narrative is frequently used in dementia studies to explain ethnic minority families' pathways to health and aged care and why there is delayed dementia diagnoses in ethnic minority communities. Such narratives may obscure the family carers' agency in negotiating services and managing personal, social and structural burdens in the lead up to diagnosis. To illuminate agency, this article describes ethnic minority families' pathways to a dementia diagnosis using the concept of sense-making. Three case studies were drawn from 56 video interviews with family carers of older adults with dementia from Chinese, Arab and Indian backgrounds. Interviews were conducted across Australia from February to August 2018, then translated, transcribed and thematically analysed. Findings suggest families did not enter into formal care because of a crisis, instead navigating fragmented systems and conflicting advice to obtain a dementia diagnosis and access to relevant care. This experience was driven by sense-making (a search for plausible explanations) that involved family carers interpreting discrepant cues in changes to the behaviour of the person with dementia over time, managing conflicting (medical) advice about these discrepancies and reinterpreting their relationships with hindsight. The sense-making concept offers a more constructive hermeneutic than the 'family crisis' narrative as it illuminates the agency of carers' in understanding changed behaviours, negotiating services and managing personal, social and structural barriers pre-diagnosis. The concept also demonstrates the need for a multimodal approach to promoting timely diagnosis of dementia in ethnic minority communities through dementia awareness and literacy campaigns as well as initiatives that address structural inequities.

How to Incorporate the Experiential Student Pharmacist Into the Pediatric Practice Setting.

Experiential education conducted in the pediatric practice setting provides student pharmacists the opportunity to learn about a unique patient population. For many students, experiential rotations may be the only form of pediatric education they receive in pharmacy school. Providing quality pediatric experiences is essential to stimulate students' interest in this practice area and train those with goals to become pediatric pharmacists. It is also important to ensure graduating pharmacists have exposure to fundamental pediatric pharmacy concepts. Although pediatric practice areas and institutions differ in patient populations and services, a well-rounded rotation experience should be provided for the pharmacy student. Preceptors must decide what concepts to teach and what activities students should be incorporated into during this experiential period. This article provides goals and activities for student pharmacists that can be included in newly designed introductory pharmacy practice experiences and advanced pharmacy practice experiences within various pediatric settings.

Magnetic resonance imaging and histopathological evaluation of equine oblique sesamoidean ligaments.

BACKGROUND: Pathology involving the oblique sesamoidean ligaments (OSLs) is commonly diagnosed during magnetic resonance imaging (MRI) of the equine distal limb. Presence of striations within the ligament and magic angle artefact can result in an incorrect diagnosis of pathological change. No studies have been performed using histopathology, the gold standard, to corroborate their imaging diagnosis. OBJECTIVES: (a) To determine which MRI characteristics are associated with normal vs abnormal OSLs and (b) to evaluate the ability of MRI to correctly identify abnormal vs normal oblique sesamoidean ligaments using histopathology as the gold standard. STUDY DESIGN: Observational, cross-sectional study. METHODS: Cadaver limbs (n = 77) were obtained from horses (n = 21) subjected to euthanasia at the hospital. MRI and histopathology was performed on each of the limbs. MRI scoring was performed for multiple MRI characteristics, and each limb was deemed normal or abnormal. Histopathology scoring was performed to give an overall score of normal or abnormal. Mixed model logistic regression was performed to evaluate which MRI characteristics were associated with normal vs abnormal OSLs using backwards elimination and a significance level of <0.1. Sensitivity and specificity were also calculated. RESULTS: The sensitivity and specificity of MRI to correctly identify abnormal OSLs was 81% (95% CI 54%-96%) and 90% (95% CI 79%-96%) respectively. Based on logistic regression, increased cross-sectional area at the origin (OR: 26.77, 95% CI 1.1-4640, P = .07), increased ligament hyperintensity (OR: 9.59, 95% CI 1.23-155; P = .04) and reduction in striations (increased hypointensity score) (OR: 7.8, 95% CI 0.72-218, P = .07) were associated with abnormal OSL. MAIN LIMITATIONS: Lameness exam was not performed on any of the horses prior to euthanasia. Findings can only be applied to chronic, degenerative changes, rather than an acute injury. CONCLUSIONS: Increased cross-sectional area and changes in the signal intensity are associated with pathology within the OSLs. Medial to lateral size asymmetry and striation pattern variation can occur in histologically normal OSLs and should be interpreted with caution if other signs of pathology are absent.

Disability, communication, and life itself in the COVID-19 pandemic.

In this article we offer an analysis of a deeply problematic and troubling dual aspect of the COVID-19 pandemic: how disability is being understood within normative accounts of health and medicine to frame, interpret, and respond to its spread and implications; what are the terms of inclusion and exclusion in altered social life in the COVID crisis; and how people with disabilities fare. We find disturbing indications of disablism and oppressive biopolitics in the 'enforcing of normalcy' that frames and dominates COVID reconstruction of social life - a situation that we suggest needs urgent deciphering, critique, and intervention.

Rare autosomal trisomies: Important and not so rare.

OBJECTIVE: Noninvasive prenatal testing (NIPT) can assess chromosomes other than 13, 18, 21, X and Y. These rare autosomal trisomies (RATs) can adversely affect pregnancy outcome. METHODS: A prospective study of NIPT using the Illumina sequencing platform assessing all chromosomes were reported for further management. RESULTS: There were 28 RATs identified in 23 388 samples (one in 835), the most common being trisomy 7 (n = 6), followed by trisomy 16 (n = 4) and trisomy 22 (n = 3). Abnormal outcomes occurred in 16 cases: miscarriage (n = 6), true fetal mosaicism (n = 5), and fetal structural anomaly on ultrasound (n = 5). Growth restriction was seen in eight cases and correlated with very low-pregnancy-associated plasma protein-A levels. Two of the 17 live born babies had a structural anomaly, and one had a phenotype similar to mosaic trisomy 16 despite a normal microarray result. CONCLUSION: Rare autosomal trisomies are not rare and often associated with poor obstetric outcomes. They should be discussed with the clinician to guide management. Pregnancy outcomes varied by chromosome being generally favourable for some (eg, trisomy 7) and poor for others (eg, trisomy 22). In the presence of a RAT, pregnancy-associated plasma protein-A is predictive of placental dysfunction and fetal growth restriction.

Isochromosome 21q is overrepresented among false-negative cell-free DNA prenatal screening results involving Down syndrome.

False-negative cell-free DNA (cfDNA) screening results involving Down syndrome are rare, but have high clinical impact on patients and their healthcare providers. Understanding the biology behind these results may allow for improved diagnostic follow-up and counseling. In 5 different centers offering cfDNA prenatal screening, 9 false-negative results were documented in 646 confirmed cases of trisomy 21; a false-negative rate of 1.4% (95% CI, 0.7-2.6). False-negative results included 4 cases of classical trisomy 21 and 5 cases with a de novo 21q;21q rearrangement. Two out of five rearrangements had molecular studies and were confirmed as isochromosomes. When combined with reports from the cfDNA screening literature, 8 out of 29 (28%) Down syndrome cases with a false-negative "non-invasive prenatal test" (NIPT) were associated with a 21q;21q rearrangement, compared with 2% reported in live born children with Down syndrome. In our laboratory series, evidence for placental or fetal mosaicism was present in 3 out of 3 true-positive cases involving a 21q;21q rearrangement and was confirmed in one false-negative case where placental material was available for study. Isochromosome 21q rearrangements are thus overrepresented among false-negative cfDNA screening results involving Down syndrome. Postzygotic isochromosome formation leading to placental mosaicism provides a biological cause for the increased prevalence of these rearrangements among false-negative cases. For clinical practice, a low trisomic fraction (z-score or equivalent measure) relative to the fetal fraction suggests placental mosaicism. Care should be taken as these cases may not reflect confined placental mosaicism, but rather full trisomy in the presence of a placenta containing normal cells.

Multi-heme proteins: nature's electronic multi-purpose tool.

While iron is often a limiting nutrient to Biology, when the element is found in the form of heme cofactors (iron protoporphyrin IX), living systems have excelled at modifying and tailoring the chemistry of the metal. In the context of proteins and enzymes, heme cofactors are increasingly found in stoichiometries greater than one, where a single protein macromolecule contains more than one heme unit. When paired or coupled together, these protein associated heme groups perform a wide variety of tasks, such as redox communication, long range electron transfer and storage of reducing/oxidizing equivalents. Here, we review recent advances in the field of multi-heme proteins, focusing on emergent properties of these complex redox proteins, and strategies found in Nature where such proteins appear to be modular and essential components of larger biochemical pathways. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems.

Impact of quaternary structure upon bacterial cytochrome c peroxidases: does homodimerization matter?

All known active forms of diheme bacterial cytochrome c peroxidase (bCcP) enzymes are described by a homodimeric state. Further, the majority of bCcPs reported display activity only when the high-potential electron transfer heme of the protein (Fe(H)) is reduced to the ferrous oxidation state. Reduction of Fe(H) results in a set of conformational changes allowing for the low-potential peroxidatic heme (Fe(L)) to adopt a high-spin, five-coordinate state that is capable of binding substrate. Here we examine the impact of dimerization upon the activity of the Shewanella oneidensis (So) bCcP by the preparation of single charge-reversal mutants at the dimer interface and use the resulting constructs to illustrate why dimerization is likely a requirement for activity in bCcPs. The E258K mutant is found to form a monomeric state in solution as characterized by size exclusion chromatography and analytical ultracentrifugation analyses. The resulting E258K monomer has an unfolding stability comparable to that of wild-type So bCcP and an activity that is only slightly diminished (k(cat)/K(m) = 23 × 10(6) M(-1) s(-1)). Spectroscopic and potentiometric analyses reveal that while the thermodynamic stability of the activated form of the enzyme is unchanged (characterized by the E(m) value of the Fe(H)(II)/Fe(H)(III) couple), the kinetic stability of the activated form of the enzyme has been greatly diminished upon generation of the monomer. Together, these data suggest a model in which dimerization of bCcP enzymes is required to stabilize the lifetime of the activated form of the enzyme against reoxidation of Fe(H) and deactivation of Fe(L).

MacA is a second cytochrome c peroxidase of Geobacter sulfurreducens.

The metal-reducing δ-proteobacterium Geobacter sulfurreducens produces a large number of c-type cytochromes, many of which have been implicated in the transfer of electrons to insoluble metal oxides. Among these, the dihemic MacA was assigned a central role. Here we have produced G. sulfurreducens MacA by recombinant expression in Escherichia coli and have solved its three-dimensional structure in three different oxidation states. Sequence comparisons group MacA into the family of diheme cytochrome c peroxidases, and the protein indeed showed hydrogen peroxide reductase activity with ABTS(-2) as an electron donor. The observed K(M) was 38.5 ± 3.7 µM H(2)O(2) and v(max) was 0.78 ± 0.03 µmol of H(2)O(2)·min(-1)·mg(-1), resulting in a turnover number k(cat) = 0.46 · s(-1). In contrast, no Fe(III) reductase activity was observed. MacA was found to display electrochemical properties similar to other bacterial diheme peroxidases, in addition to the ability to electrochemically mediate electron transfer to the soluble cytochrome PpcA. Differences in activity between CcpA and MacA can be rationalized with structural variations in one of the three loop regions, loop 2, that undergoes conformational changes during reductive activation of the enzyme. This loop is adjacent to the active site heme and forms an open loop structure rather than a more rigid helix as in CcpA. For the activation of the protein, the loop has to displace the distal ligand to the active site heme, H93, in loop 1. A H93G variant showed an unexpected formation of a helix in loop 2 and disorder in loop 1, while a M297H variant that altered the properties of the electron transfer heme abolished reductive activation.

Geobacter sulfurreducens cytochrome c peroxidases: electrochemical classification of catalytic mechanisms.

Bacterial cytochrome c peroxidase (CcP) enzymes are diheme redox proteins that reduce hydrogen peroxide to water. They are canonically characterized by a peroxidatic (called L, for "low reduction potential") active site heme and a secondary heme (H, for "high reduction potential") associated with electron transfer, and an enzymatic activity that exists only when the H-heme is prereduced to the Fe(II) oxidation state. The prereduction step results in a conformational change at the active site itself, where a histidine-bearing loop will adopt an "open" conformation allowing hydrogen peroxide to bind to the Fe(III) of the L-heme. Notably, the enzyme from Nitrosomonas europaea does not require prereduction. Previously, we have shown that protein film voltammetry (PFV) is a highly useful tool for distinguishing the electrocatalytic mechanisms of the Nitromonas type of enzyme from other CcPs. Here, we apply PFV to the recently described enzyme from Geobacter sulfurreducens and the Geobacter S134P/V135K double mutant, which have been shown to be similar to members of the canonical subclass of peroxidases and the Nitrosomonas subclass of enzymes, respectively. Here we find that the wild-type Geobacter CcP is indeed similar electrochemically to the bacterial CcPs that require reductive activation, yet the S134P/V135K mutant shows two phases of electrocatalysis: one that is low in potential, like that of the wild-type enzyme, and a second, higher-potential phase that has a potential dependent upon substrate binding and pH yet is at a potential that is very similar to that of the H-heme. These findings are interpreted in terms of a model in which rate-limiting intraprotein electron transfer governs the catalytic performance of the S134P/V135K enzyme.