Mental health in society's margins: poor n-3 PUFA intake and psychological well-being of homeless youth.

Dietary intake of long-chain n-3 PUFA (n-3 PUFA), particularly EPA and DHA, has been associated with psychological well-being, but little is known about the n-3 PUFA intake of homeless youth. The current study determined the association between depression and anxiety symptoms and n-3 PUFA intake and erythrocytes status in homeless youth. Totally, 114 homeless youth aged 18-24 years were recruited from a drop-in centre. n-3 PUFA dietary intake was assessed using an FFQ, and erythrocytes status was determined by gas chromatography (GC). Linear regression models were used to determine the relationship between psychological well-being and n-3 PUFA intake and status. The mean intakes of EPA and DHA for all participants (0·06 ± 0·13 g/d and 0·11 ± 0·24 g/d) were well below recommended levels, and mean erythrocytes EPA + DHA (n-3 index) in the cohort (2·42 %) was lower than reported for healthy, housed adolescents and those with clinical depression. There was no association of n-3 PUFA intake and erythrocytes status with either depression or anxiety. However, the relationships of depression with dietary EPA (P = 0·017) and DHA (P = 0·008), as well as erythrocytes DHA (P = 0·007) and n 3-index (P = 0·009), were significantly moderated by sex even after adjusting for confounders. Specifically, among females, as the intake and status of these n-3 PUFA decreased, depression increased. Our findings show poor dietary intake and low erythrocytes status of n-3 PUFA among homeless youth, which is associated with depressive symptoms among females.

Accelerated cell culture process development and characterization for cilgavimab/tixagevimab (AZD7442) for the prevention and treatment of COVID-19.

The global COVID-19 pandemic ignited an unprecedented race to develop vaccines and antibody therapeutics. AstraZeneca's pursuit to provide AZD7442 (EVUSHELD), two long-acting, SARS-CoV-2 spike receptor binding domain-specific neutralizing monoclonal antibodies, to individuals at risk on highly accelerated timelines challenged our traditional ways of process development and spurred the rapid adoption of novel approaches. Conventional upstream development processes were replaced by agile strategies that combined technological advances and highly accelerated workflows. With calculated business risks and close cross-functional collaborations, this process paved the way for hyper accelerated antibody development from discovery through manufacturing, process validation, emergency use authorization filing, and global regulatory approvals. The result was initiation of commercial manufacturing at a contract manufacturing organization less than 6 months from the selection of cilgavimab and tixagevimab-a process that historically has taken close to 10 years.

Disrupted caregiving behavior as a mediator of the relation between disrupted prenatal maternal representations and toddler social-emotional functioning.

The development of maternal representations of the child during pregnancy guides a mother's thoughts, feelings, and behavior toward her child. The association between prenatal representations, particularly those that are disrupted, and toddler social-emotional functioning is not well understood. The present study examined associations between disrupted prenatal representations and toddler social-emotional functioning and to test disrupted maternal behavior as a mediator of this association. Data were drawn from 109 women from a larger prospective longitudinal study (N=120) of women and their young children. Prenatal disrupted maternal representations were assessed using the Working Model of the Child Interview disrupted coding scheme, while disrupted maternal behavior was coded 12-months postpartum from mother-infant interactions. Mother-reported toddler social-emotional functioning was assessed at ages 12 and 24 months. Disrupted prenatal representations significantly predicted poorer toddler social-emotional functioning at 24 months, controlling for functioning at 12 months. Further, disrupted maternal behavior mediated the relation between disrupted prenatal representations and toddler social-emotional problems. Screening for disrupted representations during pregnancy is needed to facilitate referrals to early intervention and decrease the likelihood of toddler social-emotional problems.

Implementing the battery-operated hand-held fan as an evidence-based, non-pharmacological intervention for chronic breathlessness in patients with chronic obstructive pulmonary disease (COPD): a qualitative study of the views of specialist respiratory clinicians.

INTRODUCTION: The battery-operated hand-held fan ('fan') is an inexpensive and portable non-pharmacological intervention for chronic breathlessness. Evidence from randomised controlled trials suggests the fan reduces breathlessness intensity and improves physical activity in patients with a range of advanced chronic conditions. Qualitative data from these trials suggests the fan may also reduce anxiety and improve daily functioning for many patients. This study aimed to explore barriers and facilitators to the fan's implementation in specialist respiratory care as a non-pharmacological intervention for chronic breathlessness in patients with chronic obstructive pulmonary disease (COPD). METHODS: A qualitative approach was taken, using focus groups. Participants were clinicians from any discipline working in specialist respiratory care at two hospitals. Questions asked about current fan-related practice and perceptions regarding benefits, harms and mechanisms, and factors influencing its implementation. Analysis used a mixed inductive/deductive approach. RESULTS: Forty-nine participants from nursing (n = 30), medical (n = 13) and allied health (n = 6) disciplines participated across 9 focus groups. The most influential facilitator was a belief that the fan's benefits outweighed disadvantages. Clinicians' beliefs about the fan's mechanisms determined which patient sub-groups they targeted, for example anxious or palliative/end-stage patients. Barriers to implementation included a lack of clarity about whose role it was to implement the fan, what advice to provide patients, and limited access to fans in hospitals. Few clinicians implemented the fan for acute-on-chronic breathlessness or in combination with other interventions. CONCLUSION: Implementation of the fan in specialist respiratory care may require service- and clinician-level interventions to ensure it is routinely recommended as a first-line intervention for chronic breathlessness in patients for whom this symptom is of concern, regardless of COPD stage.

Intergenerational transmission of trauma from mother to infant: the mediating role of disrupted prenatal maternal representations of the child.

Data from a multi-method, longitudinal study involving a community sample (N = 120) of pregnant women aged 18-42 were used to examine disrupted maternal representations of the child as a mechanism of the transmission of trauma from mother to infant. Using structural equation modeling, the best fitting model indicated that severity of mothers' childhood interpersonal trauma was associated with severity of disruption in prenatal representations of the child, which in turn was associated with less secure infant-mother attachment at 1 year of age. There was a significant indirect effect of maternal childhood interpersonal trauma on infant-mother attachment insecurity via disrupted prenatal maternal representations. Findings highlight an important mechanism of trauma transmission that could be targeted in interventions with mother-infant dyads.

Childhood abuse, posttraumatic stress symptoms, and alcohol misuse among African-American women.

The study explored associations among childhood abuse, post-traumatic stress symptoms (PTSS), and alcohol misuse in a sample of low-income African-American women (N = 172). Using bootstrapping techniques, a mediation effect was found of childhood physical and emotional abuse on alcohol misuse via PTSS symptom severity, avoidance, and hyperarousal, as well as for childhood sexual abuse on alcohol misuse via PTSS symptom severity and hyperarousal. Our results suggest that PTSS indicators, particularly symptom severity and hyperarousal, may be important mechanisms underlying the association of experiences of abuse during childhood and alcohol misuse in adulthood.

Introduction of a Management Toolkit for Lewy Body Dementia: A Pilot Cluster-Randomized Trial.

BACKGROUND: Lewy body dementia, comprising both dementia with Lewy bodies and Parkinson's disease dementia, is challenging to manage because of a complex symptom profile and lack of clear evidence-based management guidelines. OBJECTIVES: We assessed the feasibility of undertaking a cluster randomized study of the introduction of an evidence-based management toolkit for Lewy body dementia, assessing the outcomes for patients and carers as secondary measures. METHODS: We randomized 23 memory/dementia, movement disorder, or nonspecialist secondary care services to the management toolkit or usual care. People with dementia with Lewy bodies or Parkinson's disease dementia underwent assessments of cognition, motor and neuropsychiatric symptoms, and global outcome at baseline and 3 and 6 months. Healthcare, personal and social care costs, and carer-related outcomes of carer stress, depression, and anxiety were also examined. RESULTS: A total of 131 participants were recruited (target 120), for whom 6-month data were available on 108 (83%). There was a benefit of being in the intervention arm for carers (reduced Zarit Burden Scale [P < 0.01], reduced depressive symptoms [P < 0.05]), who also reported less marked patient deterioration on the global outcome measure (P < 0.05). There were no significant differences in other outcomes or in costs between groups. CONCLUSIONS: The introduction of an evidence-based management toolkit for Lewy body dementia was feasible and associated with some benefits, especially for carers. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Examining the utility of the Violence Prevention Climate scale: In a metropolitan Australian general hospital.

AIM AND OBJECTIVES: To evaluate and examine the utility of the Violence Prevention Climate scale by generalist healthcare professionals. BACKGROUND: Workplace violence in general hospital settings remains a challenge for healthcare organisations. High rates of violence are still being reported towards healthcare workers, despite organisational violence prevention strategies being implemented. There is a major challenge to healthcare organisation in the measurement of the effectiveness of these interventions, traditionally completed via the reporting and monitoring of workplace violent incidents. A novel approach to measuring workplace violence is by studying hospital atmosphere or climate. DESIGN: A cross-sectional survey using the STARD guidelines was used. METHODS: The Violence Prevention Climate scale was completed by 194 healthcare staff working in the emergency department, medical/surgical wards, respiratory/infectious disease, spinal care, renal unit, corrections health, and rehabilitation and community services of a major Australian tertiary referral hospital. The Violence Prevention Climate scale has previously been validated and used in mental health settings, but not general hospital settings. A content analysis of an open-ended question on violence prevention management strategies was also conducted. RESULTS: Comprising of 14 items with two factors (patients and staff), the study revealed a 9-item staff factor scale that can be used in the general hospital setting, the patient factor did not show adequate reliability. The content analysis revealed seven categories of staff identified violence prevention and management strategies. CONCLUSIONS: The use of the 9-item scale across an organisation annually, or added to existing organisational workforce surveys, could prove to be practical way of measuring the social climate of violence in a general hospital setting. RELEVANCE TO CLINICAL PRACTICE: The results of which could guide clinical practice, workplace safety, policy and educational initiatives for the prevention and management of workplace violence.

A Narrative Review for Perioperative Physicians of the 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants.

In 2017 the American College of Cardiology issued an Expert Consensus Decision Pathway dedicated specifically to the management of bleeding in patients on anticoagulants. The consensus document is both timely and important as indications for more novel anticoagulants expand rapidly. The document reviews in detail recommendations for interruption, management and re-initiation of anticoagulation in bleeding scenarios. Numerous points within the document are relevant to perioperative physicians managing patients on anticoagulation with either bleeding complications or undergoing surgical procedures. The intent of this narrative review is to highlight the salient points within the expert consensus for perioperative physicians.

Receptor for advanced glycation end products is targeted by FBXO10 for ubiquitination and degradation.

The receptor for advanced glycation end products (RAGE) is a highly expressed cell membrane receptor serving to anchor lung epithelia to matrix components, and it also amplifies inflammatory signaling during acute lung injury. However, mechanisms that regulate its protein concentrations in cells remain largely unknown. Here we show that RAGE exhibits an extended life span in lung epithelia (t½ 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through activation of protein kinase Cζ (PKCζ), which phosphorylates RAGE. PKCζ overexpression enhances RAGE degradation, while PKCζ knockdown stabilizes RAGE protein levels and prevents ODN2006-mediated degradation. We identify that RAGE is targeted by the ubiquitin E3 ligase subunit F-box protein O10 (FBXO10), which associates with RAGE to mediate its ubiquitination and degradation. FBXO10 depletion in cells stabilizes RAGE and is required for ODN2006-mediated degradation. These data suggest that modulation of regulators involved in ubiquitin-mediated disposal of RAGE might serve as unique molecular inputs directing RAGE cellular concentrations and downstream responses, which are critical in an array of inflammatory disorders, including acute lung injury.-Evankovich, J., Lear, T., Mckelvey, A., Dunn, S., Londino, J., Liu, Y., Chen, B. B., Mallampalli, R. K. Receptor for advanced glycation end products is targeted by FBXO10 for ubiquitination and degradation.

RING finger protein 113A regulates C-X-C chemokine receptor type 4 stability and signaling.

As an α-chemokine receptor specific for stromal-derived-factor-1 (SDF-1, also called CXCL12), C-X-C chemokine receptor type 4 (CXCR4) plays a vital role in chemotactically attracting lymphocytes during inflammation. CXCR4 also regulates HIV infection due to its role as one of the chemokine coreceptors for HIV entry into CD4+ T cells. Chemokine receptors and their signaling pathways have been shown to be regulated by the process of ubiquitination, a posttranslational modification, guided by ubiquitin E3 ligases, which covalently links ubiquitin chains to lysine residues within target substrates. Here we describe a novel mechanism regulating CXCR4 protein levels and subsequent CXCR4/CXCL12 signaling pathway through the ubiquitination and degradation of the receptor in response to ligand stimulation. We identify that an uncharacterized really interesting new gene (RING) finger ubiquitin E3 ligase, RING finger protein 113A (RNF113A), directly ubiquitinates CXCR4 in cells, leading to CXCR4 degradation, and therefore disrupts the signaling cascade. We determined that the K331 residue within CXCR4 is essential for RNF113A-mediated ubiquitin conjugation. Overexpression of RNF113A significantly reduces CXCL12-induced kinase activation in HeLa cells, whereas RNF113A knockdown enhances CXCL12-induced downstream signaling. Further, RNF113A expression and silencing directly affect cell motility in a wound healing assay. These results suggest that RNF113A plays an important role in CXCR4 signaling through the ubiquitination and degradation of CXCR4. This mechanistic study might provide new understanding of HIV immunity and neutrophil activation and motility regulated by CXCR4.

THE CAREGIVING HELPLESSNESS QUESTIONNAIRE: EVIDENCE FOR VALIDITY AND UTILITY WITH MOTHERS OF INFANTS.

Severe disruptions in the caregiving system can lead to disorganized caregiving characterized by maternal helplessness and fear. Such caregivers abdicate their caregiving role and fail to provide protection to the child. The measurement of disorganized caregiving has historically been limited to lengthy, labor-intensive interviews, indicating a need for other feasible tools to assess this important construct. Furthermore, few studies have investigated correlates of disorganized caregiving. Participants included 120 diverse, primarily economically disadvantaged women who were part of a longitudinal study examining psychosocial risk factors before and after the birth of a child. Participants completed the Caregiving Helplessness Questionnaire (CHQ; C. George & J. Solomon, 2011) along with measures assessing maternal mental health, trauma exposure, parenting stress, and infant socioemotional adjustment. Results indicated that caregiver helplessness and fear, based on the CHQ, were positively associated with maternal depression, parenting stress, and perceptions of infant socioemotional problems. Importantly, results also revealed significant associations between current maternal trauma experiences and mothers' reports of helplessness and fear. Findings from the present study indicate that the CHQ may be a valid screening tool for disorganized caregiving among mothers of infants. In addition, a number of maternal experiences may be related to disorganized caregiving following the birth of a child.

Histone deacetylase 2 (HDAC2) protein-dependent deacetylation of mortality factor 4-like 1 (MORF4L1) protein enhances its homodimerization.

Histone acetyltransferase mortality factor 4-like 1 (MORF4L1) is a relatively new histone acetyltransferase component that exists as a homodimer to exert its epigenetic function. The mechanism of MORF4L1 self-assembly is unknown. Here we report that Lys-148 deacetylation is indispensable for facilitating MORF4L1 self-assembly into a homodimeric unit. Among a stretch of ∼10 amino acids in the NH2 terminus between the chromodomain and MORF4-related gene (MRG) domain within MORF4L1, Lys-148 is normally acetylated. Substitution of Lys-148 with arginine augments MORF4L1 self-assembly. However, acetylation mimics of MORF4L1, including K148L and K148Q, abolished its self-assembly of the histone acetyltransferase component. HDAC2, a deacetylase, interacts with and keeps MORF4L1 in a deacetylation status at Lys(148) that triggers MORF4L1 self-assembly. Knockdown of HDAC2 reduces MORF4L1 self-assembly. HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, thus facilitating the functionality of complex formation to repress cell proliferation.

Three-dimensional structure of victorivirus HvV190S suggests coat proteins in most totiviruses share a conserved core.

Double-stranded (ds)RNA fungal viruses are currently assigned to six different families. Those from the family Totiviridae are characterized by nonsegmented genomes and single-layer capsids, 300-450 Å in diameter. Helminthosporium victoriae virus 190S (HvV190S), prototype of recently recognized genus Victorivirus, infects the filamentous fungus Helminthosporium victoriae (telomorph: Cochliobolus victoriae), which is the causal agent of Victoria blight of oats. The HvV190S genome is 5179 bp long and encompasses two large, slightly overlapping open reading frames that encode the coat protein (CP, 772 aa) and the RNA-dependent RNA polymerase (RdRp, 835 aa). To our present knowledge, victoriviruses uniquely express their RdRps via a coupled termination-reinitiation mechanism that differs from the well-characterized Saccharomyces cerevisiae virus L-A (ScV-L-A, prototype of genus Totivirus), in which the RdRp is expressed as a CP/RdRp fusion protein due to ribosomal frameshifting. Here, we used transmission electron cryomicroscopy and three-dimensional image reconstruction to determine the structures of HvV190S virions and two types of virus-like particles (capsids lacking dsRNA and capsids lacking both dsRNA and RdRp) at estimated resolutions of 7.1, 7.5, and 7.6 Å, respectively. The HvV190S capsid is thin and smooth, and contains 120 copies of CP arranged in a "T = 2" icosahedral lattice characteristic of ScV-L-A and other dsRNA viruses. For aid in our interpretations, we developed and used an iterative segmentation procedure to define the boundaries of the two, chemically identical CP subunits in each asymmetric unit. Both subunits have a similar fold, but one that differs from ScV-L-A in many details except for a core α-helical region that is further predicted to be conserved among many other totiviruses. In particular, we predict the structures of other victoriviruses to be highly similar to HvV190S and the structures of most if not all totiviruses including, Leishmania RNA virus 1, to be similar as well.

Targeting F box protein Fbxo3 to control cytokine-driven inflammation.

Cytokine-driven inflammation underlies the pathobiology of a wide array of infectious and immune-related disorders. The TNFR-associated factor (TRAF) proteins have a vital role in innate immunity by conveying signals from cell surface receptors to elicit transcriptional activation of genes encoding proinflammatory cytokines. We discovered that a ubiquitin E3 ligase F box component, termed Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by mediating the degradation of the TRAF inhibitory protein, Fbxl2. Analysis of the Fbxo3 C-terminal structure revealed that the bacterial-like ApaG molecular signature was indispensible for mediating Fbxl2 disposal and stimulating cytokine secretion. By targeting this ApaG motif, we developed a highly unique, selective genus of small-molecule Fbxo3 inhibitors that by reducing TRAF protein levels, potently inhibited cytokine release from human blood mononuclear cells. The Fbxo3 inhibitors effectively lessened the severity of viral pneumonia, septic shock, colitis, and cytokine-driven inflammation systemically in murine models. Thus, pharmacological targeting of Fbxo3 might be a promising strategy for immune-related disorders characterized by a heightened host inflammatory response.

Integrated cost-effectiveness analysis of agri-environmental measures for water quality.

This paper presents an application of integrated methodological approach for identifying cost-effective combinations of agri-environmental measures to achieve water quality targets. The methodological approach involves linking hydro-chemical modelling with economic costs of mitigation measures. The utility of the approach was explored for the River Dee catchment in North East Scotland, examining the cost-effectiveness of mitigation measures for nitrogen (N) and phosphorus (P) pollutants. In-stream nitrate concentration was modelled using the STREAM-N and phosphorus using INCA-P model. Both models were first run for baseline conditions and then their effectiveness for changes in land management was simulated. Costs were based on farm income foregone, capital and operational expenditures. The costs and effects data were integrated using 'Risk Solver Platform' optimization in excel to produce the most cost-effective combination of measures by which target nutrient reductions could be attained at a minimum economic cost. The analysis identified different combination of measures as most cost-effective for the two pollutants. An important aspect of this paper is integration of model-based effectiveness estimates with economic cost of measures for cost-effectiveness analysis of land and water management options. The methodological approach developed is not limited to the two pollutants and the selected agri-environmental measures considered in the paper; the approach can be adapted to the cost-effectiveness analysis of any catchment-scale environmental management options.

Psychologists' Contributions to Patient-Centered Medical Homes.

Mounting evidence supports the value of integrated healthcare and the need for interprofessional practice within patient-centered medical homes (PCMH). Incorporating behavioral health services is key to fully implementing the PCMH concept. Unfortunately, psychologists have not been front and center in this integrative and interprofessional care movement nor have they typically received adequate training or experience to work effectively in these integrated care programs. This article builds the case for the value of PCMHs, particularly those that incorporate behavioral health services. Attention is paid to the diverse roles psychologists play in these settings, including as direct service providers, consultants, teachers/supervisors, scholars/program evaluators, and leaders. There is a discussion of the competencies psychologists must possess to play these roles effectively. Future directions are discussed, with a focus on ways psychologists can bolster the PCMH model by engaging in interprofessional partnerships related to education and training, practice, research, and leadership.