Expanding the international conversation with fathers' mental health: toward an era of inclusion in perinatal research and practice.

Paternal mental health is beginning to be recognized as an essential part of perinatal health. Historically, fathers were not recognized as being at risk for perinatal mental illnesses or relevant to maternal and infant health outcomes. The purpose of this paper is to provide an overview of paternal perinatal mental health, leading tools to assess paternal depression and anxiety, the impact of paternal mental health on mother and child health, and future directions for the field. An international team of paternal perinatal mental health experts summarized the key findings of the field. Fathers have an elevated risk of depression and anxiety disorders during the perinatal period that is associated with maternal depression and can impact their ability to support mothers. Paternal mental health is uniquely associated with child mental health and developmental outcomes starting from infancy and continuing through the child lifespan. Tailored screening approaches for paternal mental health are essential to support fathers early in the perinatal period, which would offset health risks for the family. Recommendations on paternal mental health are provided on four key areas to support father perinatal mental health: (1) intervention research, (2) clinical training, (3) national policy, and (4) the inclusion of fathers in the focus of the International Marcé Society for Perinatal Mental Health.

Four maternal characteristics determine the 12-month course of chronic severe postpartum depressive symptoms.

BACKGROUND: Postpartum depression is a heterogeneous disorder in phenotype and etiology. Characterizing the longitudinal course of depressive symptoms over the first year after birth and identifying variables that predict distinct symptom trajectories will expedite efficient mental health treatment planning. The purpose was to determine 12-month trajectories of postpartum depressive symptoms, identify characteristics that predict the trajectories, and provide a computational algorithm that predicts trajectory membership. METHODS: A prospective cohort of women delivering at an academic medical center (2006-2011) was recruited from an urban women's hospital in Pittsburgh, PA. Women with a postpartum depressive disorder (n = 507) participated and completed symptom severity assessments at 4-8 weeks (intake), 3 months, 6 months, and 12 months. Women were predominantly Caucasian (71.8%), married (53.3%), and college educated (38.7%). Clinician interviews of depressive symptom severity, medical and psychiatric history, assessment of function, obstetric experience, and infant status were conducted. RESULTS: Analyses resulted in identification of three distinct trajectories of depressive symptoms: (1) gradual remission (50.4%), (2) partial improvement (41.8%), and (3) chronic severe (7.8%). Key predictive characteristics of the chronic severe versus gradual remission and partial improvement trajectories included parity, education, and baseline global functioning and depression severity. We were able to predict trajectory membership with 72.8% accuracy from these characteristics. CONCLUSIONS: Four maternal characteristics predicted membership in the chronic severe versus gradual remission and partial improvement trajectories with 72.8% accuracy. The trajectory groups comprise clinically relevant subgroups with the potential for tailored treatments to reduce the disease burden of postpartum depression.

Development and Validation of a Father Involvement in Health Measure.

Father involvement has been associated with positive child social, emotional, psychological, developmental, and health outcomes. However, tools for measuring father involvement have not kept pace with the expanding understanding of the roles of fathers, and in the area of child health, are blunt. The purpose of this study was to develop and validate a self-report measure of father involvement in preschooler's health, the Father Involvement in Health-Pre-School (FIH-PS). In phase 1 item generation, 47 items were developed based on previous qualitative work and vetted through cognitive interviews with 21 fathers of children ages 3-5 (preschool). In phase 2 psychometric validation, 560 fathers of 3-5 year olds (n=392 resident, n=168 non-resident) completed the FIH-PS item bank. Participants were predominantly white (64%), had private health insurance (53%), had a mean age of 33 years, and half were married. Item Response Theory was used to determine measurement scoring. The FIH-PS scale was reduced from a 47-item bank to a total of 20 items supporting a 4-factor scale made up of Acute Illness, General Well-being, Emotional Health, and Role Modeling. Following exploratory (n=280) and confirmatory factor (n=280) analyses, the scale followed a bifactor structure, was internally consistent (Cronbach's α=0.953), and discriminated among fathers with lower involvement. A sum-to-T-score crosswalk table was produced to standardize the scores along a normal distribution (mean=50, S=10, range 10.8-71.3). Future research and clinical applications of the FIH-PS are discussed.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

Are children with chronic illnesses requiring dietary therapy at risk for disordered eating or eating disorders? A systematic review.

OBJECTIVE: Pediatric chronic illnesses (CI) can affect a child's mental health. Chronic illnesses with treatment regimens that specify a therapeutic diet may place the child at increased risk for disordered eating and specific eating disorders (ED). The aim of this review is to examine the relation between diet-treated CI and disordered eating and to determine the order of onset to infer directionality. Diet-treated CI is hypothesized to precede and to be associated with disordered eating. METHOD: A comprehensive search of empirical articles that examine the relation between diet-treated CI (diabetes, cystic fibrosis, celiac disease, gastrointestinal disorders, and inflammatory bowel diseases) and disordered eating was conducted in Medline and PsycINFO using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A table of the sample's characteristics, ED measures, major pertinent findings, and the onset of CI in relation to ED were provided. RESULTS: Diet-treated CI was associated with disordered eating and ED. Diet-treated CI had onset prior to disordered eating in most studies, except for inflammatory bowel diseases. Disordered eating and unhealthy weight management practices put children at risk for poor medical outcomes. DISCUSSION: Interventions for diet-treated CI require a focus on diet and weight, but may increase the risk for disordered eating. Future research is needed to elucidate the mechanisms that transform standard treatment practices into pathological eating, including characteristics and behaviors of the child, parents/care providers, family, and treatment providers.

Alterations in the Atlantic cod (Gadus morhua) hepatic thiol-proteome after methylmercury exposure.

Proteomic studies in general have demonstrated that the most effective and thorough analysis of biological samples requires subfractionation and/or enrichment prior to downstream processing. In the present study, Atlantic cod (Gadus morhua) liver samples were fractionated using activated thiol sepharose to isolate hepatic proteins containing free/reactive cysteines. This subset of proteins is of special interest when studying the physiological effects attributed to methylmercury (MeHg) exposure. Methylmercury is a persistent environmental contaminant that has a potent affinity toward thiol groups, and can directly bind proteins via available cysteine residues. Further, alterations in the cod thiol-proteome following MeHg exposure (2 mg/kg body weight) were explored with two-dimensional gel electrophoresis combined with downstream mass spectrometry analyses for protein identifications. Thirty-five protein spots were found to respond to MeHg exposure, and 13 of these were identified when searching cod-specific databases with acquired mass spectrometry data. Among the identified thiol-containing proteins, some are known to respond to MeHg treatment, including constituents of the cytoskeleton, and proteins involved in oxidative stress responses, protein synthesis, protein folding, and energy metabolism. Methylmercury also appeared to affect cod heme metabolism/turnover, producing significantly altered levels of hemoglobin and hemopexin in liver following metal exposure. The latter finding suggests that MeHg may also affect the hematological system in Atlantic cod.

Effects of permethrin on biomarkers in Mediterranean clams (Ruditapes decussatus).

The present study was focused on the assessment of Catalase (CAT) and Acetylcholinesterase (AChE) activities in Mediterranean clams (Ruditapes decussatus) exposed to 50, 100 and 150 µg/L of Permethrin for 5, 10, 15, 20 and 25 days. In water, the measured concentrations of Permethrin in the treated aquariums were respectively 16.66, 38.24 and 55.61 µg/L. Results showed that CAT activity was increased after 5 days of exposure to high concentration reaching maximum value of 10.14 µmol/min/mg proteins after 25 days. However, no significant changes in AChE activity after 5 days of exposure were detected in all treated groups. AChE activity was significantly inhibited after 10 days with 100 and 150 µg/L and still depending on concentration and time. Maximum inhibition of AChE activity was reached after 25 days with the highest concentration of Permethrin. Our data indicated that exposure to Permethrin modifies biomarker profiles inducing oxidative stress and reducing AChE activity in Mediterranean clams.

The importance of perinatal non-birthing parents' mental health and involvement for family health.

Perinatal mental health research typically focuses on the birthing parent's experiences and their influence on birth/child outcomes, while not considering non-birthing parents in similar depth. Non-birthing parents are also at increased risk for mental illness during the perinatal period, and non-birthing parents' health and involvement affect the health of birthing people, fetuses, and newborns, necessitating greater understanding of non-birthing parents' contributions to family functioning. This review examines perinatal mental health disorders in non-birthing parents, their relationship quality with the birthing parent, and how the non-birthing parent's mental health and involvement affects the health outcomes of the birthing parent and the child. Recommendations are provided for healthcare professionals who work with perinatal patients and their families to engage non-birthing parents, learn about non-birthing parent health, and facilitate connections to care. By doing so, professionals working with perinatal patients can optimize health outcomes for their patients and the family as a whole.

Perinatal depression screening in healthy start: an evaluation of the acceptability of technical assistance consultation.

In 2001, Healthy Start was required to screen for maternal depression. To support this mandate, technical assistance (TA) consultations were provided to eleven programs. Participant evaluations assessed TA recipients' views, a foundational level of program evaluation. Staff evaluated TA presentations immediately; and directors assessed its helpfulness in a 6-month and a 5-year follow-up. Staff believed their knowledge increased significantly; the majority rated TA presentations as "useful" to "very useful." Most directors rated TA as "useful" or "very useful" in achieving TA goals, reported having "few" or "no" obstacles in screening, and rated staff as "willing" or "very willing" to screen. A range of educational programs have been developed to assist the implementation of maternal depression screening. The current evaluation indicates that diverse types of programs held positive views of TA consultation and believed it was effective. The success of the method argues for further development.

Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Partner report of paternal depression using the Edinburgh Postnatal Depression Scale-Partner.

Similar to maternal depression, paternal depression may have adverse effects on the family environment (e.g., partner mental health, child behavior). Detection of paternal depression is rare because the maternal-child health care system usually only screens for maternal depression. The scarcity of paternal depression screening and detection is due to fathers not usually being involved in the maternal-child health care system and, therefore, unavailable for depression screening. The purpose of this study was to assess the psychometric characteristics of the Edinburgh Postnatal Depression Scale-Partner Version (EPDS-P) in detecting paternal depression through maternal report. The EPDS-P, rated by the mother, was found to be a reliable and valid measure of paternal depression when compared to other well-validated measures of depression. The EPDS-P has clinical utility in the maternal-child health care system by making it possible to screen for paternal depression without the father being present. Proxy screening for paternal depression can be beneficial for early detection and treatment of paternal depression both in the perinatal period and through a child's early life. Detection and treatment of paternal depression reduces the risk of long-term depression in fathers.

A comparison of symptoms of bipolar and unipolar depression in postpartum women.

BACKGROUND: Distinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders. METHODS: We performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4-6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS). RESULTS: The sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse. LIMITATIONS: Only women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data. CONCLUSIONS: Severity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse.

Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.

We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample ß-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.

Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods.

BACKGROUND: Both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have MIC clinical breakpoints (CBPs) for fluconazole (FLU) and Candida. EUCAST CBPs are species-specific, and apply only to C. albicans, C. tropicalis and C. parapsilosis, while CLSI CBPs apply to all species. We reassessed the CLSI CBPs for FLU and Candida in light of recent data. METHODS: We examined (1) molecular mechanisms of resistance and cross-resistance profiles, (2) wild-type (WT) MICs and epidemiological cutoff values (ECVs) for FLU and major Candida species by both CLSI and EUCAST methods, (3) determination of essential (EA) and categorical agreement (CA) between CLSI and EUCAST methods, (4) correlation of MICs with outcomes from previously published data using CLSI and EUCAST methods, and (5) pharmacokinetic and pharmacodynamic considerations. We applied these findings to propose new species-specific CLSI CBPs for FLU and Candida. RESULTS: WT distributions from large collections of Candida revealed similar ECVs by both CLSI and EUCAST methods (0.5-1 mcg/ml for C. albicans, 2 mcg/ml for C. parapsilosis and C. tropicalis, 32 mcg/ml for C. glabrata, and 64-128 for C. krusei). Comparison of CLSI and EUCAST MICs reveal EA and CA of 95% and 96%, respectively. Datasets correlating CLSI and EUCAST FLU MICs with outcomes revealed decreased response rates when MICs were > 4 mcg/ml for C. albicans, C. tropicalis and C. parapsilosis, and > 16 mcg/ml for C. glabrata. CONCLUSIONS: Adjusted CLSI CBPs for FLU and C. albicans, C. parapsilosis, C. tropicalis (S, ≤ 2 mcg/ml; SDD, 4 mcg/ml; R, ≥ 8 mcg/ml), and C. glabrata (SDD, ≤ 32 mcg/ml; R, ≥ 64 mcg/ml) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs.

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease.

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.

Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods.

Antifungal susceptibility testing of Aspergillus species has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recent studies suggest the emergence of strains of Aspergillus fumigatus with acquired resistance to azoles. The mechanisms of resistance involve mutations in the cyp51A (sterol demethylase) gene, and patterns of azole cross-resistance have been linked to specific mutations. Studies using the EUCAST broth microdilution (BMD) method have defined wild-type (WT) MIC distributions, epidemiological cutoff values (ECVs), and cross-resistance among the azoles. We tested a collection of 637 clinical isolates of A. fumigatus for which itraconazole MICs were < or = 2 microg/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of < or = 1 microg/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of < or = 0.25 microg/ml was established for posaconazole. Our results demonstrate that the WT distribution and ECVs for A. fumigatus and the mold-active triazoles were the same when determined by the CLSI or the EUCAST BMD method. A collection of 43 isolates for which itraconazole MICs fell outside of the ECV were used to assess cross-resistance. Cross-resistance between itraconazole and posaconazole was seen for 53.5% of the isolates, whereas cross-resistance between itraconazole and voriconazole was apparent in only 7% of the isolates. The establishment of the WT MIC distribution and ECVs for the azoles and A. fumigatus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.

Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis.

Members of the TGF-beta superfamily are important regulators of skeletal development. TGF-betas signal through heteromeric type I and type II receptor serine/threonine kinases. When over-expressed, a cytoplasmically truncated type II receptor can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR). To determine the role of TGF-betas in the development and maintenance of the skeleton, we have generated transgenic mice (MT-DNIIR-4 and -27) that express the DNIIR in skeletal tissue. DNIIR mRNA expression was localized to the periosteum/perichondrium, syno-vium, and articular cartilage. Lower levels of DNIIR mRNA were detected in growth plate cartilage. Transgenic mice frequently showed bifurcation of the xiphoid process and sternum. They also developed progressive skeletal degeneration, resulting by 4 to 8 mo of age in kyphoscoliosis and stiff and torqued joints. The histology of affected joints strongly resembled human osteo-arthritis. The articular surface was replaced by bone or hypertrophic cartilage as judged by the expression of type X collagen, a marker of hypertrophic cartilage normally absent from articular cartilage. The synovium was hyperplastic, and cartilaginous metaplasia was observed in the joint space. We then tested the hypothesis that TGF-beta is required for normal differentiation of cartilage in vivo. By 4 and 8 wk of age, the level of type X collagen was increased in growth plate cartilage of transgenic mice relative to wild-type controls. Less proteoglycan staining was detected in the growth plate and articular cartilage matrix of transgenic mice. Mice that express DNIIR in skeletal tissue also demonstrated increased Indian hedgehog (IHH) expression. IHH is a secreted protein that is expressed in chondrocytes that are committed to becoming hypertrophic. It is thought to be involved in a feedback loop that signals through the periosteum/ perichondrium to inhibit cartilage differentiation. The data suggest that TGF-beta may be critical for multifaceted maintenance of synovial joints. Loss of responsiveness to TGF-beta promotes chondrocyte terminal differentiation and results in development of degenerative joint disease resembling osteoarthritis in humans.