Postnatal depression in British mothers of African and Caribbean origin: a randomised controlled trial of learning through play plus culturally adapted cognitive behaviour therapy compared with psychoeducation.

Background: One in every three women worldwide experiences postnatal depression after childbirth, with long-term negative consequences on their children. The mainstream mental healthcare provision for British mothers of African/Caribbean origin is mostly unsuccessful due to a lack of culturally appropriate care. Methods: The study adopts a mixed-methods randomised controlled trial (RCT) design. A 12-session (60 minutes each) of online Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) intervention was employed for treating postnatal depression in comparison with psychoeducation (PE). Participants aged 19-53 were screened for depression using the Patient Health Questionnaire (PHQ-9). N=130 participants who scored >5 on PHQ-9 were randomised into LTP+CaCBT (n=65) or PE (n=65) groups. N=12 focus groups (LTP+CaCBT, n=6; PE, n=6) and n=15 individual interviews (LTP+CaCBT, n=8; PE, n=7) were conducted, transcribed verbatim and analysed. Results: Satisfaction with intervention (LTP+CaCBT, 72.9%; PE, 65.2%); retention rates (LTP+CaCBT, 91%; PE, 71%); reduction in postnatal depression was higher in LTP+CaCBT on PHQ-9 Md=1.00 with z= -4.046; compared to PE, Md=1.00 with z= -1.504. Both groups showed reduced levels of anxiety on GAD-7 with no significant difference. Emerging themes from the qualitative findings showed increased positive moods, reduced worries about parenting difficulties and the facilitative role of remote intervention. Conclusions: LTP+CaCBT intervention is culturally appropriate and acceptable and reduces postnatal depression in British mothers of African/Caribbean origin. A fully powered RCT is recommended to evaluate the clinical and cost-effectiveness of LTP+CaCBT, including the child's outcomes compared with routine treatment as usual. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04820920.

Interventions for Self-Harm and Suicidal Ideation in Africa: A Systematic Review.

BACKGROUND: Self-harm and suicidal ideation are increasing public health concerns globally and are paramount in Africa. Therefore, a review of suicidal ideation and self-harm interventions would be beneficial in identifying culturally appropriate interventions for the African context. METHOD: The Population, phenomenon of Interest and Context (PICo) model was adopted to formulate the review strategy. Thus, the Population (Africans), phenomenon of Interest (intervention) and Context (self-harm and suicidal ideation). We used this PICo strategy which is a modified version of PICO for qualitative studies. Framework with Boolean operators (AND/OR/NOT) was further used to ensure rigor through search terms such as ("Suicide" OR "suicidal ideation") AND ("Intervention" OR "Treatment" OR "Therapy" OR "Psychological" OR "Psychosocial" OR "Culturally adapted") AND "Africa" OR "African countries." Six databases were searched (Embase, PsycINFO, ProQuest Central, Cochrane Controlled Trials Register, Medline, and Web of Science) for published articles between 2000 and March 2023. N = 12 studies met the inclusion criteria, and the relevant data extracted were synthesized and thematically analyzed. The review protocol was pre-registered on the PROSPERO Registry (no. CRD42021283795). RESULTS: N = 12 studies met the inclusion criteria, and the following themes emerged from the synthesized literature and analyses of current African approaches to curbing self-harm and suicidal ideation: (a) Western medical and compassion-focused intervention (b) the helpful role of traditional healing and healers (c) psychoeducation and self-help techniques (d) use of technology and a nation-wide approach. CONCLUSION: Self-harm and suicidal ideation are global health concerns. To address this health concern in Africa, the authors recommend culturally adapted psychological interventions to be tested via randomized control trials.

Perspectives on Self-Harm and Suicidal Ideation in Nigeria: A Mixed-Methods Study of Patients, Family Caregivers, Clinicians, and the Public.

BACKGROUND: Suicide and self-harm are global disease burden that contributes significantly to years of lost life and mortality. Despite the increasing rates of suicide and self-harm in Nigeria, this topic is understudied. METHODS: A mixed-methods design was adopted. Study 1 interviewed n = 18 participants (n = 11 clinicians; n = 5 patients with a history of self-harm and suicide ideation; and n = 2 caregivers). All interviews were audio-recorded, transcribed verbatim, and analyzed using IPA. Study 2 surveyed n = 562 non-clinical sample about their tolerance toward self-harm and the data was analyzed using One-way ANOVA in SPSS. RESULTS: Study 1 qualitative findings showed substance use, perceived rejection and social isolation were considered predisposing factors for suicide and self-harm. Cultural and religious beliefs shaped help-seeking behaviours. Although Study 2 found no significant differences in demographic characteristics concerning public tolerance toward persons with a history of self-harm, 64% believed that individuals who died by suicide would face punishment after death; 51% believed that victims of attempted suicide are a source of shame to their families; and 33.8% agreed that dying by suicide is the correct behaviour. CONCLUSIONS: Patients with a history of self-harm and suicidal ideation consider family members and close friends as valuable sources of support. Due to the potential clinical implication of cultural and religious beliefs, as shown in the present study's findings, the authors recommend a co-development of culturally appropriate psychological intervention for persons with a history of self-harm and suicidal ideation to be tested in randomized control trials.

Pelagic metagenome-assembled genomes from an estuarine salinity gradient in San Francisco Bay.

San Francisco Bay (SFB) is a large and highly human-impacted estuarine system. We produced 449 metagenome-assembled genomes from SFB waters, collected along the salinity gradient, providing a rich data set to compare the metabolic potential of microorganisms from different salinity zones within SFB and to other estuarine systems.

Ecophysiology and genomics of the brackish water adapted SAR11 subclade IIIa.

The Order Pelagibacterales (SAR11) is the most abundant group of heterotrophic bacterioplankton in global oceans and comprises multiple subclades with unique spatiotemporal distributions. Subclade IIIa is the primary SAR11 group in brackish waters and shares a common ancestor with the dominant freshwater IIIb (LD12) subclade. Despite its dominance in brackish environments, subclade IIIa lacks systematic genomic or ecological studies. Here, we combine closed genomes from new IIIa isolates, new IIIa MAGS from San Francisco Bay (SFB), and 460 highly complete publicly available SAR11 genomes for the most comprehensive pangenomic study of subclade IIIa to date. Subclade IIIa represents a taxonomic family containing three genera (denoted as subgroups IIIa.1, IIIa.2, and IIIa.3) that had distinct ecological distributions related to salinity. The expansion of taxon selection within subclade IIIa also established previously noted metabolic differentiation in subclade IIIa compared to other SAR11 subclades such as glycine/serine prototrophy, mosaic glyoxylate shunt presence, and polyhydroxyalkanoate synthesis potential. Our analysis further shows metabolic flexibility among subgroups within IIIa. Additionally, we find that subclade IIIa.3 bridges the marine and freshwater clades based on its potential for compatible solute transport, iron utilization, and bicarbonate management potential. Pure culture experimentation validated differential salinity ranges in IIIa.1 and IIIa.3 and provided detailed IIIa cell size and volume data. This study is an important step forward for understanding the genomic, ecological, and physiological differentiation of subclade IIIa and the overall evolutionary history of SAR11.

Bipolar disorders in Nigeria: a mixed-methods study of patients, family caregivers, clinicians, and the community members' perspectives.

BACKGROUND: Bipolar Disorders (BDs) are chronic mental health disorders that often result in functional impairment and contribute significantly to the disability-adjusted life years (DALY). BDs are historically under-researched compared to other mental health disorders, especially in Sub-Saharan Africa and Nigeria. DESIGN: We adopted a mixed-methods design. Study 1 examined the public knowledge of BDs in relation to sociodemographic outcomes using quantitative data whilst Study 2 qualitatively assessed the lived experiences of patients with BDs, clinicians, and family caregivers. METHODS: In Study 1, a non-clinical sample of n = 575 participants responded to a compact questionnaire that examined their knowledge of BDs and how they relate to certain sociodemographic variables. One-way ANOVA was used to analyse quantitative data. Study 2 interviewed N = 15 participants (n = 5 patients with BDs; n = 7 clinicians; n = 3 family caregivers). These semi-structured interviews were audio-recorded, transcribed, and thematically analysed. RESULTS: In Study 1, findings showed no statistically significant differences, suggesting low awareness of BDs, especially among vulnerable populations such as young people and older adults. However, there was a trajectory in increased knowledge of BDs among participants between the ages of 25-44 years and part-time workers compared to other ages and employment statuses. In Study 2, qualitative findings showed that BDs are perceived to be genetically and psycho-socially induced by specific lived experiences of patients and their family caregivers. Although psychotropic medications and psychotherapy are available treatment options in Nigeria, cultural and religious beliefs were significant barriers to treatment uptake. CONCLUSIONS: This study provides insight into knowledge and beliefs about BDs, including the lived experiences of patients with BDs, their caregivers and clinicians in Nigeria. It highlights the need for further studies assessing Nigeria's feasibility and acceptability of culturally adapted psychosocial interventions for patients with BDs.

Culturally adapted psychological intervention for treating maternal depression in British mothers of African and Caribbean origin: A randomized controlled feasibility trial.

BACKGROUND: Women are likely to suffer from maternal depression due to childbirth difficulties and parenting responsibilities, leading to long-term negative consequences on their children and families. British mothers of African/Caribbean origin uptake of mental healthcare is low due to the lack of access to culturally appropriate care. METHODS: A mixed-methods randomized controlled feasibility trial was adopted to test the appropriateness and acceptability of Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) for treating maternal depression compared with Psychoeducation (PE). Mothers (N = 26) aged 20-55 were screened for depression using the Patient Health Questionnaire (PHQ-9). Those who scored >5 on PHQ-9 were further interviewed using the Revised Clinical Interview Schedule to confirm the diagnosis and randomized into LTP+CaCBT (n = 13) or PE (n = 13) groups. Assessments were taken at baseline, end of the intervention at 3- and 6-months post-randomization. N = 2 focus groups (LTP+CaCBT, n = 12; PE, n = 7) and N = 8 individual interviews were conducted (LTP+CaCBT, n = 4; PE, n = 4). RESULTS: The LTP+CaCBT group showed higher acceptability, feasibility and satisfaction levels than the PE group. Participants experienced the intervention as beneficial to their parenting skills with reduced depression and anxiety in the LTP+CaCBT compared to the PE group. CONCLUSIONS: This is the first feasibility trial of an integrated online parenting intervention for British African and Caribbean mothers. The results indicated that culturally adapted LTP+CaCBT is acceptable and feasible. There is a need to study the clinical and cost-effectiveness of LTP+CaCBT in an appropriately powered randomized control trial and include the child's outcomes. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (no. NCT04820920).

Expanding CRISPR repertoire using CjCas9 as a smaller editing tool.

The field of gene editing continues to expand significantly and is entering a time of unprecedented utility. Academia and industry look to conquer genetic-based disease with viral and non-viral-delivered CRISPR-Cas9. The most widely used Cas9 protein is derived from Streptococcus pyrogenes (SpCas9), which lends itself to being too large for AAV viral delivery. Cas9 orthologue proteins have diverse size and dependent on bacteria of origin. This diversity has given rise to Cas9 proteins smaller in size while maintaining gene editing abilities. In this article, authors have focused on the use of CjCas9, whose smaller size allows for packaging in AAV and maintains high on-target gene editing. The locus APOC3 was identified for eventual targeting/integration in humans where cardioprotective properties are predicted. To confirm in vivo targeting of this locus, a humanized mouse model was developed due to the absence of the APOC3 locus in mice. These studies looked to answer long-standing questions on integrated gene stability, promoter/low gene integration, and the duration of therapeutic efficacy of the integrated gene.

Sacroiliac joint pain in adolescents: Diagnostic and treatment challenges.

The aim of this review was to assess diagnostic and treatment challenges of adolescents with SI joint pain. We diagnosed 13 of the patients who were referred to our chronic pain clinic because of low back pain (30%) with SI joint pain based on provocative tests response. We performed SI joint steroid infiltration. Six patients (46%) felt better immediately after the procedure and 1 (8%) patient had a one-side only pain relief after a bilateral block. Four of these patients (31%) did not experience any further episode of pain during the follow-up and three patients reported recurring pain on average 2 months after the initial procedure. The 2nd procedure was successful in two patients and the third one experienced pain again 12 months later, requiring a third successful infiltration. Six patients (46%) experienced pain again within a few hours or days after the infiltration and their pain score were unchanged compared with what they had reported prior to the procedure. We were unable to place the needle within the joint under fluoroscopy in 1 patient; however, we were successful repeating the procedure under CT guidance. One patient experienced a motor and sensory block in the distribution of the sciatic nerve immediately after the procedure, which resolved within 24 and 48 hours, respectively. SI joint pain is a distinctive pathology that can be present in children and adolescents and is often overlooked by practitioners. Its diagnosis and management are challenging in this population as it is in adults. SI joint steroids injections may play a role in the management of these patients.

Extracellular vesicle-induced cyclic AMP signaling.

Second messenger signaling is required for cellular processes. We previously reported that extracellular vesicles (EVs) from stimulated cultured endothelial cells contain the biochemical second messenger, cAMP. In the current study, we sought to determine whether cAMP-enriched EVs induce second messenger signaling pathways in naïve recipient cells. Our results indicate that cAMP-enriched EVs increase cAMP content sufficient to stimulate PKA activity. The implications of our work are that EVs represent a novel intercellular mechanism for second messenger, specifically cAMP, signaling.

Comparative Analysis of Axial Length Measurements by Optical Biometers Based on Partial Coherence Interferometry Versus Optical Low-Coherence Interferometry: An Office Audit.

Purpose In this study, we aimed to compare axial length (AL) measurements of the IOLMaster 500 (Carl Zeiss Meditec AG, Jena, Germany), based on partial coherence interferometry (PCI) versus the Aladdin (Topcon Healthcare, Oakland, NJ), based on optical low-coherence interferometry (OLCI), in a clinical setting. Methods A retrospective analysis of the records of patients presenting for cataract surgery at an ophthalmology practice between October 2019 and March 2020 was performed. All patients had biometry measurements on the IOLMaster 500 and the Aladdin. Data collected included patient demographics, cataract morphology and type, and AL measurements. The IOLMaster 500 and Aladdin measurements were compared using the unpaired t-test and Chi-squared test. Results In total, 393 eyes (197 patients) were included (91 males, 107 females) in the study. The IOLMaster 500 was unable to successfully obtain AL measurements in seven eyes (1.8%) and the Aladdin in 26 eyes (6.6%). The difference was statistically significant (p=0.0007). Advanced and central posterior subcapsular cataracts were common in eyes that had unsuccessful measurements. In the eyes successfully measured, the mean AL for the IOLMaster was 24.04 ±1.32 mm, while it was 24.04 ±1.34 mm for the Aladdin. However, this difference was not statistically significant (p=0.9165). Conclusion The IOLMaster 500 performed better in terms of the number of eyes for which AL measurements were successfully obtained compared to the Aladdin. This may be partly related to high volumes of advanced cataracts treated at our practice. However, this being a retrospective study, a cause-and-effect relationship could not be established.

Predicting exon criticality from protein sequence.

Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting Exon skipping Based on Protein amino acid SequenceS), to assess the criticality of exon inclusion based solely on information contained in the amino acid sequence upstream and downstream of the exon junctions. By focusing on protein sequence, Exon ByPASS predicts exon skipping independent of tissue and species in the absence of any intronic information. We validate model predictions using transcriptomic and proteomic data and show that the model can capture exon skipping in different tissues and species. Additionally, we reveal potential therapeutic opportunities by predicting synthetically skippable exons and neo-junctions arising in cancer cells.

Genome-Resolved Metagenomic Insights into Massive Seasonal Ammonia-Oxidizing Archaea Blooms in San Francisco Bay.

Ammonia-oxidizing archaea (AOA) are key for the transformation of ammonia to oxidized forms of nitrogen in aquatic environments around the globe, including nutrient-rich coastal and estuarine waters such as San Francisco Bay (SFB). Using metagenomics and 16S rRNA gene amplicon libraries, we found that AOA are more abundant than ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB), except in the freshwater stations in SFB. In South SFB, we observed recurrent AOA blooms of "Candidatus Nitrosomarinus catalina" SPOT01-like organisms, which account for over 20% of 16S rRNA gene amplicons in both surface and bottom waters and co-occur with weeks of high nitrite concentrations (>10 µM) in the oxic water column. We observed pronounced nitrite peaks occurring in the autumn for 7 of the last 9 years (2012 to 2020), suggesting that seasonal AOA blooms are common in South SFB. We recovered two high-quality AOA metagenome-assembled genomes (MAGs), including a Nitrosomarinus-like genome from the South SFB bloom and another Nitrosopumilus genome originating from Suisun Bay in North SFB. Both MAGs cluster with genomes from other estuarine/coastal sites. Analysis of Nitrosomarinus-like genomes show that they are streamlined, with low GC content and high coding density, and harbor urease genes. Our findings support the unique niche of Nitrosomarinus-like organisms which dominate coastal/estuarine waters and provide insights into recurring AOA blooms in SFB. IMPORTANCE Ammonia-oxidizing archaea (AOA) carry out key transformations of ammonia in estuarine systems such as San Francisco Bay (SFB)-the largest estuary on the west coast of North America-and play a significant role in both local and global nitrogen cycling. Using metagenomics and 16S rRNA gene amplicon libraries, we document a massive, recurrent AOA bloom in South SFB that co-occurs with months of high nitrite concentrations in the oxic water column. Our study is the first to generate metagenome-assembled genomes (MAGs) from SFB, and through this process we recovered two high-quality AOA MAGs, one of which originated from bloom samples. These AOA MAGs yield new insight into the Nitrosopumilus and Nitrosomarinus-like lineages and their potential niches in coastal and estuarine systems. Nitrosomarinus-like AOA are abundant in coastal regions around the globe, and we highlight the common occurrence of urease genes, low GC content, and range of salinity tolerances within this lineage.

Systemic biodistribution and hepatocyte-specific gene editing with CRISPR/Cas9 using hyaluronic acid-based nanoparticles.

The goal of this study was to evaluate hepatocyte-specific gene editing, via systemic administration of hyaluronic acid (HA)-based nanoparticles in naïve CD-1 mice. Using HA-poly(ethylene imine) (HA-PEI) and HA-PEI-mannose nanoparticles with differential mannose density (1X and 2X), we have evaluated systemic biodistribution and hepatocyte-specific delivery using IVIS imaging and flow cytometry. Additionally, we have investigated hepatocyte-specific delivery and transfection of CRISPR/Cas9 gene editing plasmid and eGFP gene payload to integrate at the Rosa26 locus. IVIS imaging showed uptake of HA-PEI nanoparticles primarily by the liver, and with addition of mannose at different concentrations, the nanoparticles showed increased uptake in both the liver and spleen. HA-PEI-mannose nanoparticles showed 55-65% uptake by hepatocytes, along with uptake by resident macrophage regardless of the mannose concentration. One of two gRNA targets showed 15% genome editing and obtained similar results for all three nanoparticle formulations. Cells positive for our gene payload were greatest with HA-PEI-mannose-1X nanoparticles where 16.2% of cells were GFP positive. The results were encouraging as proof of concept for the development of a non-viral biodegradable and biocompatible polymeric delivery system for gene editing specifically targeting hepatocytes upon systemic administration.

Diverse ecophysiological adaptations of subsurface Thaumarchaeota in floodplain sediments revealed through genome-resolved metagenomics.

The terrestrial subsurface microbiome contains vastly underexplored phylogenetic diversity and metabolic novelty, with critical implications for global biogeochemical cycling. Among the key microbial inhabitants of subsurface soils and sediments are Thaumarchaeota, an archaeal phylum that encompasses ammonia-oxidizing archaea (AOA) as well as non-ammonia-oxidizing basal lineages. Thaumarchaeal ecology in terrestrial systems has been extensively characterized, particularly in the case of AOA. However, there is little knowledge on the diversity and ecophysiology of Thaumarchaeota in deeper soils, as most lineages, particularly basal groups, remain uncultivated and underexplored. Here we use genome-resolved metagenomics to examine the phylogenetic and metabolic diversity of Thaumarchaeota along a 234 cm depth profile of hydrologically variable riparian floodplain sediments in the Wind River Basin near Riverton, Wyoming. Phylogenomic analysis of the metagenome-assembled genomes (MAGs) indicates a shift in AOA population structure from the dominance of the terrestrial Nitrososphaerales lineage in the well-drained top ~100 cm of the profile to the typically marine Nitrosopumilales in deeper, moister, more energy-limited sediment layers. We also describe two deeply rooting non-AOA MAGs with numerous unexpected metabolic features, including the reductive acetyl-CoA (Wood-Ljungdahl) pathway, tetrathionate respiration, a form III RuBisCO, and the potential for extracellular electron transfer. These MAGs also harbor tungsten-containing aldehyde:ferredoxin oxidoreductase, group 4f [NiFe]-hydrogenases and a canonical heme catalase, typically not found in Thaumarchaeota. Our results suggest that hydrological variables, particularly proximity to the water table, impart a strong control on the ecophysiology of Thaumarchaeota in alluvial sediments.

Structural insights into bifunctional thaumarchaeal crotonyl-CoA hydratase and 3-hydroxypropionyl-CoA dehydratase from Nitrosopumilus maritimus.

The ammonia-oxidizing thaumarchaeal 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle is one of the most energy-efficient CO2 fixation cycles discovered thus far. The protein encoded by Nmar_1308 (from Nitrosopumilus maritimus SCM1) is a promiscuous enzyme that catalyzes two essential reactions within the thaumarchaeal 3HP/4HB cycle, functioning as both a crotonyl-CoA hydratase (CCAH) and 3-hydroxypropionyl-CoA dehydratase (3HPD). In performing both hydratase and dehydratase activities, Nmar_1308 reduces the total number of enzymes necessary for CO2 fixation in Thaumarchaeota, reducing the overall cost for biosynthesis. Here, we present the first high-resolution crystal structure of this bifunctional enzyme with key catalytic residues in the thaumarchaeal 3HP/4HB pathway.

Maternal mental health and child well-being in Nigeria: A systematic review.

Maternal mental health distress has a disease burden of severe adverse effects for both mother and child. This review identified maternal mental health concerns, their impact on child growth and the current practice of maternal healthcare for both mothers and their children in Nigeria. The Population, phenomenon of Interest and Context (PICo) model was adopted to formulate the review strategy, and five databases were searched for published articles between 1999 and 2019. Databases include Scopus, PubMed, ProQuest, Applied Social Science Index and Abstracts and Web of Science. Boolean operators (AND/OR/NOT) helped to ensure rigorous use of search terms which include 'maternal', 'pre/peri/postnatal', 'mental health', 'mental illness', 'disorders', 'intervention,' 'Nigeria', 'child', 'infant growth', and 'wellbeing'. Thirty-four studies met the inclusion criteria, and extracted data were qualitatively synthesised and analysed thematically. Five themes emerged. These include (i) marital difficulties, (ii) relationship status of the mother, (iii) child's gender, (iv) mode of child delivery and (v) child growth and development. The review showed a significant paucity of literature on the impact of specific maternal mental health problems on child physical growth and cognitive development. We concluded that culturally appropriate and evidence-based psychological interventions for maternal mental health problems would benefit Nigerian indigenous mothers. Therefore, the study recommends randomised controlled trials that are culturally appropriate and cost-effective for distressed mothers with children.

Mental health experiences of mothers in Jos, Nigeria: An interpretative phenomenological analysis.

OBJECTIVES: There is an increasing mental health disease burden in mothers with infants and young children, especially in low- and middle-income countries such as Nigeria. Children of distressed mothers suffer early-life exposure from the effects of maternal distress which contributes to the risk of physical and mental health problems in their childhood and beyond. This study explored mental health lived experiences of mothers in Jos, Nigeria. METHODS: Purposive and Snowball sampling techniques were adopted, and a total of 40 mothers participated with 8 to 11 participants in one of the four focus group discussions. Participants were between the ages of 18 and 43 years, self-identified as mothers with each having a child between the ages of 3 and 48 months. Each focus group lasted approximately 60 minutes and was audio-recorded. Interviews were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS: Three overarching themes emerged from the data set such as (1) experience of persisting psychological distress from the time of labour/birth; (2) cultural practices that influence feelings; and (3) anxiety due to limited knowledge about childcare, access to support and healthy food. CONCLUSION: Maternal mental health in Nigeria is under-researched and distressed mothers have limited knowledge about evidence-based early child development. The study recommends developing and testing culturally appropriate parenting interventions in Jos, Nigeria. This is likely to be beneficial for the mother and may also improve child health outcomes.

Psychological interventions for maternal depression among women of African and Caribbean origin: a systematic review.

BACKGROUND: Maternal depression is a leading cause of disease burden for women worldwide; however, there are ethnic inequalities in access to psychological interventions in high-income countries (HICs). Culturally appropriate interventions might prove beneficial for African and Caribbean women living in HICs as ethnic minorities. METHODS: The review strategy was formulated using the PICo (Population, phenomenon of Interest, and Context) framework with Boolean operators (AND/OR/NOT) to ensure rigour in the use of search terms ("postpartum depression", "maternal depression", "postnatal depression", "perinatal depression" "mental health", "psychotherapy" "intervention", "treatment", "black Caribbean", "black African", "mothers" and "women"). Five databases, including Scopus, PsycINFO, Applied Social Science Index and Abstracts (ASSIA), ProQuest Central and Web of Science, were searched for published articles between 2000 and July 2020. 13 studies met the inclusion criteria, and the relevant data extracted were synthesised and thematically analysed. RESULTS: Data syntheses and analyses of included studies produced four themes, including (1) enhance parenting confidence and self-care; (2) effective mother-child interpersonal relationship; (3) culturally appropriate maternal care; and (4) internet-mediated care for maternal depression. CONCLUSION: In the quest to address maternal mental health disparities among mothers of African and Caribbean origin in HICs, the authors recommend culturally adapted psychological interventions to be tested in randomised control trials.

Discovery and optimization of a novel anti-GUCY2c x CD3 bispecific antibody for the treatment of solid tumors.

We report here the discovery and optimization of a novel T cell retargeting anti-GUCY2C x anti-CD3ε bispecific antibody for the treatment of solid tumors. Using a combination of hybridoma, phage display and rational design protein engineering, we have developed a fully humanized and manufacturable CD3 bispecific antibody that demonstrates favorable pharmacokinetic properties and potent in vivo efficacy. Anti-GUCY2C and anti-CD3ε antibodies derived from mouse hybridomas were first humanized into well-behaved human variable region frameworks with full retention of binding and T-cell mediated cytotoxic activity. To address potential manufacturability concerns, multiple approaches were taken in parallel to optimize and de-risk the two antibody variable regions. These approaches included structure-guided rational mutagenesis and phage display-based optimization, focusing on improving stability, reducing polyreactivity and self-association potential, removing chemical liabilities and proteolytic cleavage sites, and de-risking immunogenicity. Employing rapid library construction methods as well as automated phage display and high-throughput protein production workflows enabled efficient generation of an optimized bispecific antibody with desirable manufacturability properties, high stability, and low nonspecific binding. Proteolytic cleavage and deamidation in complementarity-determining regions were also successfully addressed. Collectively, these improvements translated to a molecule with potent single-agent in vivo efficacy in a tumor cell line adoptive transfer model and a cynomolgus monkey pharmacokinetic profile (half-life>4.5 days) suitable for clinical development. Clinical evaluation of PF-07062119 is ongoing.