Suicide crises among women and mothers during and around the time of pregnancy: Prevalence and timing of initial contact with first responders and health services.

OBJECTIVES: Suicide is a leading cause of maternal mortality. Suicidality during and around the time of pregnancy can have detrimental impacts on a child's development and outcomes. This paper examines prevalence, demographic characteristics, and timing of initial contact with first responders and health services for a cohort of women who experienced suicidality during and around the time of pregnancy. METHODS: Findings are drawn from the Partners in Prevention (PiP) study, a population-wide linked data set of suicide-related attendances by police or paramedics in Queensland, Australia. A sub-cohort of women was identified, who were between 6 months preconception and 2 years postpartum at the time of a suicide-related contact with police or paramedics (PiP-Maternal). Findings are compared to other girls and women who had a suicide-related contact with police or paramedics (PiP-Female). Prevalence, demographic characteristics, timing of contact with first responders and health services, re-presentations, and mortality are reported. RESULTS: The PiP-Maternal cohort comprised 3020 individuals and 3400 births. Women in the PiP-Maternal cohort were younger, more likely to be of Aboriginal and/or Torres Strait Islander descent and live outside of a major city than the PiP-Female cohort. There were high rates of out-of-hours calls to police and ambulance, and similar perceived seriousness of the call between women in the PiP-Maternal and PiP-Female cohorts. Women in the PiP-Maternal cohort were less likely to be admitted to an emergency department within 24 hours, even after matching on covariates. Prevalence of suicidality for women who were pregnant and up to 2 years postpartum was 1.32% (95% CI = [1.27, 1.37]). CONCLUSION: Vulnerabilities and high rates of contact with police or paramedics, coupled with lower levels of follow-up, highlight the critical need to improve service responses for women with mental health needs during these phases of life.

Primary mental health prevention in partners of mothers with a major mental illness: SMS4Dads.

BACKGROUND: Mental health promotion and prevention with expecting and new fathers has historically been challenging. Approximately 10% of this population report experiencing depression in the post-partum period and 18% report experiencing anxiety. This population may be further at risk if their partner has a mental illness. OBJECTIVE: To assess if information provided by SMS may be a way to reach a vulnerable population of new fathers with partners who have a mental illness. METHOD: Twenty-three new and expecting fathers who have partners with a mental illness were engaged in a qualitative assessment of their experience with the SMS4Dads programme. RESULTS: This analysis showed that at risk new fathers appreciated the information received during the programme and reported acting on this, making changes in the way they interact with their children. CONCLUSION: The combination of timely, accurate and practical information delivered in a novel way, likely contributed to the reports of improved interactions within the family unit.

Evaluation of a collaborative group intervention for mothers with moderate to severe perinatal mental illness and their infants in Australia.

Perinatal mental illness is a known risk to maternal-infant attachment and healthy infant development. Mothers experiencing complex mental health issues in the first year following birth are less likely to become involved in parenting programs or day stay interventions because of their mental health difficulties and perceived stigma. Currently, most perinatal day or group treatment programs only include the mother and not their infant. This paper describes "Together in Mind," a perinatal and infant mental health day program developed by the Queensland Centre for Perinatal and Infant Mental Health, targeting mothers with moderate to severe mental illness and their infants under 12 months. The service model was a 6-week, 1 day per week psychoeducation intervention. Psychoeducational material and support were provided across each day session by an adult perinatal mental health clinician, an infant mental health clinician, and a child health nurse working in collaboration. The program was trialed across seven Hospital and Health Service sites in Queensland, Australia, during 2016-18. In total, 24 group day programs were delivered with 84 mothers and their infants. Pre and post intervention quantitative measures and a post-program qualitative survey about participant satisfaction were collected. Statistically significant improvements in all quantitative measures showed a large to medium effect size on the: Health of the Nation Outcome Scale (HoNOS) (d = 0.82; p < .000); Depression, Anxiety and Stress Scale (DASS-21) (d = 0.5; p < .000); Karitane Parenting Confidence Scale (KPCS) (d = 0.63; p < .000); Maternal Postnatal Attachment Scale (MPAS) (d = 0.49; p < .000), Ages and Stages Questionnaire: Social-Emotional (6 months) (d = 0.83; p < .000). The results indicate collaboration and early intervention contributes to strengthening the emerging development of the maternal-infant relationship within the context of complex maternal mental health issues.

Con frecuencia se excluye a las madres perinatales con asuntos de salud mental severos y complejos de programas de apoyo a la crianza, lo cual presenta un riesgo para la relación materno-infantil y el desarrollo saludable del infante. El Centro de Queensland para la Salud Perinatal y la Salud Mental del Infante puso a prueba 'Juntos en la Mente,' un programa perinatal y de salud mental infantil de un día con énfasis en madres con salud mental entre moderada y severa e infantes de menos de 12 meses. La colaborativa intervención la llevaron a cabo 3 servicios públicos de salud mental y de salud infantil a lo largo de 7 lugares de Servicio de Hospital y Salud en Queensland, Australia, durante 2016-18. En el período de 2 años, se trabajó con 24 grupos de 6 semanas de duración y con 84 madres que completaron las medidas cuantitativas de pre- y post- intervención, así como encuestas posteriores al programa para reportar la experiencia de las participantes. Se dieron mejorías estadísticamente significativas en todas las medidas cuantitativas, lo cual muestra un efecto de tamaño entre grande y mediano: La Escala de Resultados de Salud de la Nación (HoNOS) (d = 0.82; p <.001); Escala de Depresión, Ansiedad y Estrés (DASS-21) (d = 0.5; p <.001); Escala Karitane de Confianza en la Crianza (KPCS) (d = 0.63; p <.001); Escala de Afectividad Materna Postnatal (MPAS) (d = 0.49; p<.001), Cuestionario de Edades y Estados: Socio-Emocional (6 meses) (d = 0.83; p <.001). Los resultados sindican intervenciones tempranas colaborativas refuerzan el naciente desarrollo de la relación materno-infantil dentro del contexto de los complejos asuntos de salud maternos.

Les mères périnatales avec des problèmes graves et complexes de santé mentale sont fréquemment exlues de programmes de soutien au parentage posant ainsi un risque à la relation maternelle-nourrisson et au développement sain de l'enfant. Le Centre de Queensland (en Australie) pour la Santé Mentale du Nourrisson a mis en place un programme 'Together in Mind', un programme de santé mentale périnatale et du nourrisson de jour ciblant les mères ayant des maladies mentales modérées à sévères avec des nourrissons de moins de 12 mois. L'intervention collaborative a été offerte par trois services publics de santé et de santé mentale de l'enfant au travers de 7 hôpitaux et sites de service de santé à Queensland en Australie entre 2016 et 2018. Durant cette période de deux ans 24 groupes de durée de 6 mois ont été formés avec 84 mères remplissant des mesures qualitatives pré-intervention et post-intervention et des questionnaires à la fin du programme, relatant l'expérience de la participante. Nous avons trouvé des améliorations statistiquement importantes dans toutes les mesures quantitatives, montrant une taille d'effet de grande à moyenne: Echelle de Résultat de Santé de la Nation (HoNOS) (d = 0,82; p <,001); Echelle de Dépression, Anxiété et Stress (DASS-21) (d = 0,5; p <,001); Echelle Karitane de Confiance de Parentage (KPCS) (d = 0,63; p <,001); Echelle d'Attachement Maternel Postnatal (MPAS) (d = 0,49; p <,001), le Questionnaire Âges et Étapes Socio-Émotionnel (6 mois) (d = 0,83; p <,001). Les résultats indiquent que l'intervention précoce collaborative renforce le développement qui pointe de la relation maternelle-nourrisson dans le contexte de problèmes de santé mentale complexe.

The identification and deletion of the polyketide synthase-nonribosomal peptide synthase gene responsible for the production of the phytotoxic triticone A/B in the wheat fungal pathogen Pyrenophora tritici-repentis.

The economically important necrotrophic fungal pathogen, Pyrenophora tritici-repentis (Ptr), causes tan spot of wheat, a disease typified by foliar necrosis and chlorosis. The culture filtrate of an Australian Ptr isolate, M4, possesses phytotoxic activity and plant bioassay guided discovery led to the purification of necrosis inducing toxins called triticone A and B. High-resolution LC-MS/MS analysis of the culture filtrate identified an additional 37 triticone-like compounds. The biosynthetic gene cluster responsible for triticone production (the Ttc cluster) was identified and deletion of TtcA, a hybrid polyketide synthase (PKS)-nonribosomal peptide synthase (NRPS), abolished production of all triticones. The pathogenicity of mutant (ttcA) strains was not visibly affected in our assays. We hypothesize that triticones possess general antimicrobial activity important for competition in multi-microbial environments.

Metabolomic profiling and genomic analysis of wheat aneuploid lines to identify genes controlling biochemical pathways in mature grain.

Metabolomics is becoming an increasingly important tool in plant genomics to decipher the function of genes controlling biochemical pathways responsible for trait variation. Although theoretical models can integrate genes and metabolites for trait variation, biological networks require validation using appropriate experimental genetic systems. In this study, we applied an untargeted metabolite analysis to mature grain of wheat homoeologous group 3 ditelosomic lines, selected compounds that showed significant variation between wheat lines Chinese Spring and at least one ditelosomic line, tracked the genes encoding enzymes of their biochemical pathway using the wheat genome survey sequence and determined the genetic components underlying metabolite variation. A total of 412 analytes were resolved in the wheat grain metabolome, and principal component analysis indicated significant differences in metabolite profiles between Chinese Spring and each ditelosomic lines. The grain metabolome identified 55 compounds positively matched against a mass spectral library where the majority showed significant differences between Chinese Spring and at least one ditelosomic line. Trehalose and branched-chain amino acids were selected for detailed investigation, and it was expected that if genes encoding enzymes directly related to their biochemical pathways were located on homoeologous group 3 chromosomes, then corresponding ditelosomic lines would have a significant reduction in metabolites compared with Chinese Spring. Although a proportion showed a reduction, some lines showed significant increases in metabolites, indicating that genes directly and indirectly involved in biosynthetic pathways likely regulate the metabolome. Therefore, this study demonstrated that wheat aneuploid lines are suitable experimental genetic system to validate metabolomics-genomics networks.

Untargeted metabolomics of human plasma reveal lipid markers unique to chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation and progressive airflow limitation, whereas idiopathic pulmonary fibrosis (IPF) is characterised by a restrictive pattern due to fibrosis and impaired gas exchange. We undertook metabolomic analysis of blood samples in IPF, COPD and healthy controls (HC) to determine differences in circulating molecules and identify novel pathogenic pathways. An untargeted metabolomics using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) was performed to profile plasma of patients with COPD (n = 21), and IPF (n = 24) in comparison to plasma from healthy controls (HC; n = 20). The most significant features were identified using multiple database matching. One-way ANOVA and variable importance in projection (VIP) scores were also used to highlight metabolites that influence the specific disease groups. Non-polar metabolites such as fatty acids (FA) and membrane lipids were well resolved and a total of 4805 features were identified. The most prominent metabolite composition differences in lipid mediators identified at ∼2-3 fold higher in both diseases compared to HC were palmitoleic acid, oleic acid and linoleic acid; and dihydrotestosterone was lower in both diseases. We demonstrated that COPD and IPF were characterised by systemic changes in lipid constituents such as essential FA sampled from circulating plasma.

Hierarchical clustering of MS/MS spectra from the firefly metabolome identifies new lucibufagin compounds.

Metabolite identification is the greatest challenge when analysing metabolomics data, as only a small proportion of metabolite reference standards exist. Clustering MS/MS spectra is a common method to identify similar compounds, however interrogation of underlying signature fragmentation patterns within clusters can be problematic. Previously published high-resolution LC-MS/MS data from the bioluminescent beetle (Photinus pyralis) provided an opportunity to mine new specialized metabolites in the lucibufagin class, compounds important for defense against predation. We aimed to 1) provide a workflow for hierarchically clustering MS/MS spectra for metabolomics data enabling users to cluster, visualise and easily interrogate the identification of underlying cluster ion profiles, and 2) use the workflow to identify key fragmentation patterns for lucibufagins in the hemolymph of P. pyralis. Features were aligned to their respective MS/MS spectra, then product ions were dynamically binned and resulting spectra were hierarchically clustered and grouped based on a cutoff distance threshold. Using the simplified visualization and the interrogation of cluster ion tables the number of lucibufagins was expanded from 17 to a total of 29.

Expansion and Conservation of Biosynthetic Gene Clusters in Pathogenic Pyrenophora spp.

Pyrenophora is a fungal genus responsible for a number of major cereal diseases. Although fungi produce many specialised or secondary metabolites for defence and interacting with the surrounding environment, the repertoire of specialised metabolites (SM) within Pyrenophora pathogenic species remains mostly uncharted. In this study, an in-depth comparative analysis of the P. teres f. teres, P teres f. maculata and P. tritici-repentis potential to produce SMs, based on in silico predicted biosynthetic gene clusters (BGCs), was conducted using genome assemblies from PacBio DNA reads. Conservation of BGCs between the Pyrenophora species included type I polyketide synthases, terpene synthases and the first reporting of a type III polyketide synthase in P teres f. maculata. P. teres isolates exhibited substantial expansion of non-ribosomal peptide synthases relative to P. tritici-repentis, hallmarked by the presence of tailoring cis-acting nitrogen methyltransferase domains. P. teres isolates also possessed unique non-ribosomal peptide synthase (NRPS)-indole and indole BGCs, while a P. tritici-repentis phytotoxin BGC for triticone production was absent in P. teres. These differences highlight diversification between the pathogens that reflects their different evolutionary histories, host adaption and lifestyles.

Untargeted gas chromatography-mass spectrometry-based metabolomics analysis of kidney and liver tissue from the Lewis Polycystic Kidney rat.

Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments. The Lewis Polycystic Kidney (LPK) rat phenotype has been characterized and classified as a model of nephronophthisis (NPHP9, caused by mutation of the Nek8 gene) for which polycystic kidneys are one of the main pathologic features. The aim of this study was to use a GC-MS-based untargeted metabolomics approach to determine key biochemical changes in kidney and liver tissue of the LPK rat. Tissues from 16-week old LPK (n = 10) and Lewis age- and sex-matched control animals (n = 11) were used. Principal component analysis (PCA) distinguished signal corrected metabolite profiles from Lewis and LPK rats for kidney (PC-1 77%) and liver (PC-1 46%) tissue. There were marked differences in the metabolite profiles of the kidney tissues with 122 deconvoluted features significantly different between the LPK and Lewis strains. The metabolite profiles were less marked between strains for liver samples with 30 features significantly different. Five biochemical pathways showed three or more significantly altered metabolites: transcription/translation, arginine and proline metabolism, alpha-linolenic and linoleic acid metabolism, the citric acid cycle, and the urea cycle. The results of this study validate and complement the current literature and are consistent with the understood pathobiology of PKD.

A rapid method for profiling of volatile and semi-volatile phytohormones using methyl chloroformate derivatisation and GC-MS.

Phytohormones are central components of complex signalling networks in plants. The interplay between these metabolites, which include abscisic acid (ABA), auxin (IAA), ethylene, jasmonic acid (JA) and salicylic acid (SA), regulate plant growth and development and modulate responses to biotic and abiotic stress. Few methods of phytohormone profiling can adequately quantify a large range of plant hormones simultaneously and without the requirement for laborious or highly specialised extraction protocols. Here we describe the development and validation of a phytohormone profiling protocol, based on methyl-chloroformate derivatisation of the plant metabolites and analysis by gas chromatography/mass spectrometry (GC-MS). We describe the analysis of 11 metabolites, either plant phytohormones or intermediates of phytohormone metabolism; ABA, azelaic acid, IAA, JA and SA, and the phytohormone precursors 1-aminocyclopropane 1-carboxylic acid, benzoic acid, cinnamic acid, 13-epi-12-oxophytodienoic acid (13-epi-OPDA), linoleic acid and linolenic acid, and validate the isolation from foliar tissue of the model legume Medicago truncatula. The preparation is insensitive to the presence of water, facilitating measurement of the volatile metabolites. Quantitation was linear over four orders of magnitude, and the limits of detection between two and 10 ng/mL for all measured metabolites using a single quadrupole GC-MS.

Effects of respiratory Mycoplasma pneumoniae infection on allergen-induced bronchial hyperresponsiveness and lung inflammation in mice.

Airway mycoplasma infection may be associated with asthma pathophysiology. However, the direct effects of mycoplasma infection on asthma remain unknown. Using a murine allergic-asthma model, we evaluated the effects of different timing of airway Mycoplasma pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of Th1 (gamma interferon [IFN-gamma]) and Th2 (interleukin 4 [IL-4]) cytokines in bronchoalveolar lavage fluid. When mycoplasma infection occurred 3 days before allergen (ovalbumin) sensitization and challenge, the infection reduced the BHR and inflammatory-cell influx into the lung. This was accompanied by a significant induction of Th1 responses (increased IFN-gamma and decreased IL-4 production). Conversely, when mycoplasma infection occurred 2 days after allergen sensitization and challenge, the infection initially caused a temporary reduction of BHR and then increased BHR, lung inflammation, and IL-4 levels. Our data suggest that mycoplasma infection could modulate both physiological and immunological responses in the murine asthma model. Our animal models may also provide a new means to understand the role of infection in asthma pathogenesis and give evidence for the asthma hygiene hypothesis.