A mixed methods systematic review exploring infant feeding experiences and support in women with severe mental illness.

There are many benefits of breastfeeding to women and their infants but meeting the recommended 6 months of exclusive breastfeeding is likely to be more challenging for women with severe mental illness (SMI). This is the first systematic review that aims to examine evidence of (a) infant feeding outcomes in women with SMI and the factors associated with this, (b) the experiences of infant feeding and infant feeding support for women with SMI, (c) interventions for supporting infant feeding among these women and (d) health care professionals' attitudes toward supporting infant feeding in women with SMI. Mixed methods systematic review was carried out using the principles of Joanna Briggs Institute's (JBI) 'convergent integrated' methodology. CINAHL, PsycINFO, Medline and MIDIRS were used to search literature between 1994 and 2022. The quality of selected articles was assessed using JBI critical appraisal tools and thematic synthesis was undertaken to obtain findings. Eighteen papers were included in the final review. Women with SMI were less likely to initiate and continue breastfeeding than women without SMI. Several challenges with breastfeeding were highlighted, and while these were often linked to women's mental health difficulties, inconsistent advice from health care professionals and poor support with breastfeeding further compounded these challenges. This review highlights that policy and practice need to take into account the individual challenges women with SMI face when planning, initiating and maintaining breastfeeding. Education and training for health care professionals are needed to enable them to provide tailored infant feeding support to women with SMI, which reflects their individual needs.

Factors Affecting Infant Feeding Practices Among Women With Severe Mental Illness.

Background: The health benefits of breastfeeding are well-established but for mothers with severe mental illness (SMI), the decision to breastfeed can be complex. Very few prior studies have investigated the infant feeding choices of women with SMI, or the factors associated with this. Our aims were to examine antenatal infant feeding intentions and infant feeding outcomes in a cohort of women admitted for acute psychiatric care in the first postpartum year. We also aimed to examine whether demographic and clinical characteristics associated with breastfeeding were similar to those found in previous studies in the general population, including age, employment, education, BMI, mode of delivery, smoking status, and social support. Methods: This study was a mixed-methods secondary analysis of a national cohort study, ESMI-MBU (Examining the effectiveness and cost-effectiveness of perinatal mental health services). Participants had been admitted to acute care with SMI in the first postpartum year. Infant feeding outcomes were retrospectively self-reported by women during a 1-month post-discharge interview. Free-text responses to questions relating to infant feeding and experience of psychiatric services were also explored using thematic analysis. Results: 144 (66.1%) of 218 women reported breastfeeding (mix feeding and exclusive breastfeeding). Eighty five percentage of the cohort had intended to breastfeed and of these, 76.5% did so. Factors associated with breastfeeding included infant feeding intentions, employment and non-Caucasian ethnicity. Although very few women were taking psychotropic medication contraindicated for breastfeeding, over a quarter (n = 57, 26.15%) reported being advised against breastfeeding because of their medication. Women were given this advice by psychiatry practitioners (40% n = 22), maternity practitioners (32.73% n = 18) and postnatal primary care (27.27% n = 15). Most women stopped breastfeeding earlier than they had planned to as a result (81.1% n = 43). Twenty five women provided free text responses, most felt unsupported with infant feeding due to inconsistent information about medication when breastfeeding and that breastfeeding intentions were de-prioritized for mental health care. Conclusion: Women with SMI intend to breastfeed and for the majority, this intention is fulfilled. Contradictory and insufficient advice relating to breastfeeding and psychotropic medication indicates that further training is required for professionals caring for women at risk of perinatal SMI about how to manage infant feeding in this population. Further research is required to develop a more in-depth understanding of the unique infant feeding support needs of women with perinatal SMI.

Caveolin-1 mediates soft scaffold-enhanced adipogenesis of human mesenchymal stem cells.

BACKGROUND: Human bone marrow-derived mesenchymal stem cells (hBMSCs) can differentiate into adipocytes upon stimulation and are considered an appropriate cell source for adipose tissue engineering. In addition to biochemical cues, the stiffness of a substrate that cells attach to has also been shown to affect hBMSC differentiation potential. Of note, most current studies are conducted on monolayer cultures which do not directly inform adipose tissue engineering, where 3-dimensional (3D) scaffolds are often used to create proper tissue architecture. In this study, we aim to examine the adipogenic differentiation of hBMSCs within soft or stiff scaffolds and investigate the molecular mechanism mediating the response of hBMSCs to substrate stiffness in 3D culture, specifically the involvement of the integral membrane protein, caveolin-1 (CAV1), known to regulate signaling in MSCs via compartmentalizing and concentrating signaling molecules. METHODS: By adjusting the photo-illumination time, photocrosslinkable gelatin scaffolds with the same polymer concentration but different stiffnesses were created. hBMSCs were seeded within soft and stiff scaffolds, and their response to adipogenic induction under different substrate mechanical conditions was characterized. The functional involvement of CAV1 was assessed by suppressing its expression level using CAV1-specific siRNA. RESULTS: The soft and stiff scaffolds used in this study had a compressive modulus of ~0.5 kPa and ~23.5 kPa, respectively. hBMSCs showed high viability in both scaffold types, but only spread out in the soft scaffolds. hBMSCs cultured in soft scaffolds displayed significantly higher adipogenesis, as revealed by histology, qRT-PCR, and immunostaining. Interestingly, a lower CAV1 level was observed in hBMSCs in the soft scaffolds, concomitantly accompanied by increased levels of Yes-associated protein (YAP) and decreased YAP phosphorylation, when compared to cells seeded in the stiff scaffolds. Interestingly, reducing CAV1 expression with siRNA was shown to further enhance hBMSC adipogenesis, which may function through activation of the YAP signaling pathway. CONCLUSIONS: Soft biomaterials support superior adipogenesis of encapsulated hBMSCs in 3D culture, which is partially mediated by the CAV1-YAP axis. Suppressing CAV1 expression levels represents a robust method in the promotion of hBMSC adipogenesis.

Assessing mental health during pregnancy: An exploratory qualitative study of midwives' perceptions.

BACKGROUND: Mental health disorders are estimated to affect between 10% and 20% of women who access maternity services and can be defined as a public health issue due to the potential consequences for women, children and families. Detecting problems early in pregnancy can significantly improve outcomes for women and their families. However, mental health problems are not being consistently identified in routine midwifery practice and little is known from current literature about midwives' practice in relation to current national guidelines or the impact models of care have on assessing maternal mental health. OBJECTIVE: To identify midwives' views about barriers and facilitators to screening for mental health in pregnancy using current UK guidelines. DESIGN: Nine community midwives from a single district general hospital in the south of England were recruited to take part in focus groups. Thematic analysis was used to extract key themes from the data. FINDINGS: Three key themes were identified from the focus groups and included system factors, social factors and trust. Barriers and facilitators to screening maternal mental health were associated with the initial 'booking' appointment' and differences in models of care. Barriers to screening were defined as high workload, poor continuity, and a lack of trust between women and midwives. CONCLUSIONS: This study highlights key barriers and facilitators associated with mental health screening during pregnancy, including issues of trust and uncertainty about women's willingness to disclose mental health conditions. Further research is required to evaluate the relationship between women and midwives in contemporary practice and the influence this may have on maternal mental health.

Cognitive dysfunction is associated with abnormal responses in cerebral blood flow in patients with single ventricular physiology: Novel insights from transcranial Doppler ultrasound.

OBJECTIVES: Improvements in the management of complex congenital heart disease, including those with single ventricle physiology, have resulted in increased survival. As this population ages, the recognition of cognitive impairment is increasingly important. At present, little is known about the potential mechanisms of cognitive dysfunction. In this cross-sectional study, we aimed to characterize the nature of abnormalities in cerebral blood flow and the relationship to cognitive deficits in adults with single ventricular physiology. PATIENTS: Ten adults with single ventricular physiology (age 18-40 years) and 12 age- and gender-matched controls underwent transcranial Doppler ultrasound and accompanying cognitive assessment. OUTCOME MEASURES: Patients underwent neuropsychological testing that assessed differing cognitive domains, with subjective cognitive decline determined from a 24-question survey. Transcranial Doppler ultrasound was used to assess baseline cerebral blood flow as well as change in cerebral blood flow velocities from baseline and during cognitive testing. Age, ethnicity, individual, and parental education levels were considered in the multivariate analyses. RESULTS: On assessment of cognitive function, the patient group performed more poorly across each of the measured domains. The control group had a significantly greater increase in cerebral blood flow in response to cognitive stimuli compared to the patient cohort; these differences in response to cognitive stimuli were seen to a similar extent across each of the measured cognitive domains. CONCLUSION: Adults with Fontan physiology are underperforming in assessments of executive function with associated abnormalities in cerebral perfusion potentially contributing to cognitive deficits.

Promotion of human mesenchymal stem cell osteogenesis by PI3-kinase/Akt signaling, and the influence of caveolin-1/cholesterol homeostasis.

INTRODUCTION: Stem cells are considered an important resource for tissue repair and regeneration. Their utilization in regenerative medicine will be aided by mechanistic insight into their responsiveness to external stimuli. It is likely that, similar to all other cells, an initial determinant of stem cell responsiveness to external stimuli is the organization of signaling molecules in cell membrane rafts. The clustering of signaling molecules in these cholesterol-rich membrane microdomains can affect the activity, specificity, cross-talk and amplification of cell signaling. Membrane rafts fall into two broad categories, non-caveolar and caveolar, based on the absence or presence, respectively, of caveolin scaffolding proteins. We have recently demonstrated that caveolin-1 (Cav-1) expression increases during, and knockdown of Cav-1 expression enhances, osteogenic differentiation of human bone marrow derived mesenchymal stem cells (MSCs). The increase in Cav-1 expression observed during osteogenesis is likely a negative feedback mechanism. We hypothesize that focal adhesion signaling pathways such as PI3K/Akt signaling may be negatively regulated by Cav-1 during human MSC osteogenesis. METHODS: Human bone marrow MSCs were isolated from femoral heads obtained after total hip arthroplasty. MSCs were incubated in standard growth medium alone or induced to osteogenically differentiate by the addition of supplements (ß-glycerophosphate, ascorbic acid, dexamethasone, and 1,25-dihydroxyvitamin D3). The activation of and requirement for PI3K/Akt signaling in MSC osteogenesis were assessed by immunoblotting for phosphorylated Akt, and treatment with the PI3K inhibitor LY294002 and Akt siRNA, respectively. The influences of Cav-1 and cholesterol membrane rafts on PI3K/Akt signaling were investigated by treatment with Cav-1 siRNA, methyl-ß-cyclodextrin, or cholesterol oxidase, followed by cellular sub-fractionation and/or immunoblotting for phosphorylated Akt. RESULTS: LY294002 and Akt siRNA inhibited MSC osteogenesis. Methyl-ß-cyclodextrin, which disrupts all membrane rafts, inhibited osteogenesis. Conversely, Cav-1 siRNA and cholesterol oxidase, which displaces Cav-1 from caveolae, enhanced Akt signaling induced by osteogenic supplements. In control cells, phosphorylated Akt began to accumulate in caveolae after 10 days of osteogenic differentiation. CONCLUSIONS: PI3K/Akt signaling is a key pathway required for human MSC osteogenesis, and it is likely that localization of active Akt in non-caveolar and caveolar membrane rafts positively and negatively contributes to osteogenesis, respectively.

Four major dietary patterns identified for a target-population of adults residing in Newfoundland and Labrador, Canada.

BACKGROUND: Very limited nutritional epidemiological studies conducted to explore the unique dietary exposure in Newfoundland and Labrador (NL). This study aims to identify and characterize major dietary patterns in the target-population from general adult NL residents and assess the associations with selected demographic factors. METHODS: A total of 192 participants, aged 35-70 years, completed and returned a food-frequency questionnaire (FFQ) and participated in a telephone interview to collect demographic information. Dietary patterns were identified by common factor analysis. Univariate and multivariate linear regression analyses were used to assess determinants of the different food consumption patterns. Pearson's correlation coefficients were calculated for food scores of each pattern, total energy, and energy-adjusted nutrient intakes. RESULTS: Factor analyses identified four dietary patterns, which were labeled as "Meat", "Vegetable/fruit", "Fish", and "Grain" patterns. In combination, the four dietary patterns explained 63% of the variance in dietary habits of the study population. Multivariate linear regression analysis indicated an increasing trend of factor scores for Meat and Grain pattern with age. Male participants were found to be more likely to choose the Meat and Fish patterns. Current smokers and those married/living together tend to choose the Grain pattern. Pearson's correlation coefficients showed positive correlations between fat and cholesterol and the Meat pattern, fiber and the Vegetable/fruits pattern, protein and the Fish pattern, and carbohydrates and the Grain pattern. CONCLUSION: This study derived four dietary patterns and obtained their significant associations with specific demographic characteristics in this population. It identified one dietary consumption pattern (Fish) not yet seen in other studied populations. These findings will update the current dietary-health information published in this province, and contribute to further research into the association between dietary practices and health.

Characterization of bone marrow-derived mesenchymal stem cells in aging.

Adult mesenchymal stem cells are a resource for autologous and allogeneic cell therapies for immune-modulation and regenerative medicine. However, patients most in need of such therapies are often of advanced age. Therefore, the effects of the aged milieu on these cells and their intrinsic aging in vivo are important considerations. Furthermore, these cells may require expansion in vitro before use as well as for future research. Their aging in vitro is thus also an important consideration. Here, we focus on bone marrow mesenchymal stem cells (BMSCs), which are unique compared to other stem cells due to their support of hematopoietic cells in addition to contributing to bone formation. BMSCs may be sensitive to age-related diseases and could perpetuate degenerative diseases in which bone remodeling is a contributory factor. Here, we review (1) the characterization of BMSCs, (2) the characterization of in vivo-aged BMSCs, (3) the characterization of in vitro-aged BMSCs, and (4) potential approaches to optimize the performance of aged BMSCs. This article is part of a Special Issue entitled "Stem Cells and Bone".

The less-often-traveled surface of stem cells: caveolin-1 and caveolae in stem cells, tissue repair and regeneration.

Stem cells are an important resource for tissue repair and regeneration. While a great deal of attention has focused on derivation and molecular regulation of stem cells, relatively little research has focused on how the subcellular structure and composition of the cell membrane influences stem cell activities such as proliferation, differentiation and homing. Caveolae are specialized membrane lipid rafts coated with caveolin scaffolding proteins, which can regulate cholesterol transport and the activity of cell signaling receptors and their downstream effectors. Caveolin-1 is involved in the regulation of many cellular processes, including growth, control of mitochondrial antioxidant levels, migration and senescence. These activities are of relevance to stem cell biology, and in this review evidence for caveolin-1 involvement in stem cell biology is summarized. Altered stem and progenitor cell populations in caveolin-1 null mice suggest that caveolin-1 can regulate stem cell proliferation, and in vitro studies with isolated stem cells suggest that caveolin-1 regulates stem cell differentiation. The available evidence leads us to hypothesize that caveolin-1 expression may stabilize the differentiated and undifferentiated stem cell phenotype, and transient downregulation of caveolin-1 expression may be required for transition between the two. Such regulation would probably be critical in regenerative applications of adult stem cells and during tissue regeneration. We also review here the temporal changes in caveolin-1 expression reported during tissue repair. Delayed muscle regeneration in transgenic mice overexpressing caveolin-1 as well as compromised cardiac, brain and liver tissue repair and delayed wound healing in caveolin-1 null mice suggest that caveolin-1 plays an important role in tissue repair, but that this role may be negative or positive depending on the tissue type and the nature of the repair process. Finally, we also discuss how caveolin-1 quiescence-inducing activities and effects on mitochondrial antioxidant levels may influence stem cell aging.

Adequacy of niacin, folate, and vitamin B12 intakes from foods among Newfoundland and Labrador adults.

PURPOSE: Adequacy of intake for niacin, folate, and vitamin B12 from food was estimated in an adult population in Newfoundland and Labrador (NL). Also considered was whether study findings support current Canadian food fortification policies. METHODS: Four hundred randomly selected adult NL residents were surveyed by telephone. Secondary analysis was performed on two 24-hour food recalls for each participant. Mean daily intakes of niacin, folate, and vitamin B12 were estimated from foods only and compared by sex/age subgroup. Adequacy of intakes was estimated. Contributions of folate by ready-to-eat cereal and bread products were also estimated. RESULTS: Intakes of all three nutrients were higher in men. In comparison with recommendations, daily niacin intakes were as follows: excessive for 21.9% of all participants (and for 56.8% of men aged 28 to 54), within the recommended range for 73.6%, and less than adequate for 4.5%. In comparison with recommendations, daily folate intakes were as follows: within the recommended range for 18.1% of participants and less than adequate for 81.9%. In comparison with recommendations, daily vitamin B12 intakes were less than adequate for 36.3% of participants. CONCLUSIONS: More than 20% of those surveyed were consuming, from food alone, niacin at levels above the maximum recommended. Food fortification policies pertaining to niacin should be revisited. In addition, despite fortification, NL adults may be consuming inadequate amounts of folate from foods.

Assessing the validity of a self-administered food-frequency questionnaire (FFQ) in the adult population of Newfoundland and Labrador, Canada.

BACKGROUND: The Food- Frequency Questionnaire (FFQ) is a dietary assessment tool frequently used in large-scale nutritional epidemiology studies. The goal of the present study is to validate a self-administered version of the Hawaii FFQ modified for use in the general adult population of Newfoundland and Labrador (NL). METHODS: Over a one year period, 195 randomly selected adults completed four 24-hour dietary recalls (24-HDRs) by telephone and one subsequent self-administered FFQ. Estimates of energy and nutrients derived from the 24-HDRs and FFQs were compared (protein, carbohydrate, fibre, fat, vitamin A, carotene, vitamin D, and calcium). Data were analyzed using the Pearson's correlation coefficients, cross-classification method, and Bland-Altman plots. RESULTS: The mean nutrient intake values of the 24-HDRs were lower than those of the FFQs, except for protein in men. Sex and energy-adjusted de-attenuated Pearson correlation coefficients for each nutrient varied from 0.13 to 0.61. Except for protein in men, all correlations were statistically significant with p < 0.05. Cross-classification analysis revealed that on average, 74% women and 78% men were classified in the same or adjacent quartile of nutrient intake when comparing data from the FFQ and 24-HDRs. Bland-Altman plots showed no serious systematic bias between the administration of the two instruments over the range of mean intakes. CONCLUSION: This 169-item FFQ developed specifically for the adult NL population had moderate relative validity and therefore can be used in studies to assess food consumption in the general adult population of NL. This tool can be used to classify individual energy and nutrient intakes into quartiles, which is useful in examining relationships between diet and chronic disease.

Caveolin-1 regulates proliferation and osteogenic differentiation of human mesenchymal stem cells.

Caveolin-1 is a scaffolding protein of cholesterol-rich caveolae lipid rafts in the plasma membrane. In addition to regulating cholesterol transport, caveolin-1 has the ability to bind a diverse array of cell signaling molecules and regulate cell signal transduction in caveolae. Currently, there is little known about the role of caveolin-1 in stem cells. It has been reported that the caveolin-1 null mouse has an expanded population of cells expressing stem cell markers in the gut, mammary gland, and brain, suggestive of a role for caveolin-1 in stem cell regulation. The caveolin-1 null mouse also has increased bone mass and an increased bone formation rate, and its bone marrow-derived mesenchymal stem cells (MSCs) have enhanced osteogenic potential. However, the role of caveolin-1 in human MSC osteogenic differentiation remains unexplored. In this study, we have characterized the expression of caveolin-1 in human bone marrow derived MSCs. We show that caveolin-1 protein is enriched in density gradient-fractionated MSC plasma membrane, consisting of ~100 nm diameter membrane-bound vesicles, and is distributed in a punctate pattern by immunofluoresence localization. Expression of caveolin-1 increases in MSCs induced to undergo osteogenic differentiation, and siRNA-mediated knockdown of caveolin-1 expression enhances MSC proliferation and osteogenic differentiation. Taken together, these findings suggest that caveolin-1 normally acts to regulate the differentiation and renewal of MSCs, and increased caveolin-1 expression during MSC osteogenesis likely acts as a negative feedback to stabilize the cell phenotype.

Dual regulation of metalloproteinase expression in chondrocytes by Wnt-1-inducible signaling pathway protein 3/CCN6.

OBJECTIVE: Wnt-1-inducible signaling pathway protein 3 (WISP-3)/CCN6 is mutated in progressive pseudorheumatoid dysplasia and may have effects on cartilage homeostasis. The aim of this study was to ascertain additional roles for WISP-3/CCN6 by determining its expression in osteoarthritic (OA) cartilage and by investigating its effects on cartilage-relevant metalloproteinase expression in immortalized (C-28/I2) and primary chondrocytes. METHODS: Cartilage steady-state levels of WISP-3/CCN6 messenger RNA and protein production were determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. WISP-3/CCN6 was overexpressed in C-28/I2 cells, and the resultant clones were analyzed by quantitative RT-PCR. The stable clones were analyzed by RT-PCR for metalloproteinase expression, and the signaling pathways involved were investigated using pharmacologic inhibition. The effects of WISP-3/CCN6 on metalloproteinase expression in primary chondrocytes were investigated using a small interfering RNA approach. RESULTS: WISP-3/CCN6 was highly expressed in OA cartilage compared with undamaged cartilage, at both the RNA and protein levels. WISP-3/CCN6 overexpression in C-28/I2 cells resulted in unexpected dual regulation of metalloproteinases; expression of the potent aggrecanase ADAMTS-5 was down-regulated 9-fold, while expression of MMP-10 was up-regulated 14-fold, and these responses were accentuated in the WISP-3/CCN6 clones grown in suspension. MMP-10 up-regulation was dependent on several MAPKs, but WISP-3/CCN6-mediated ADAMTS-5 repression was independent of these pathways and was partially relieved by activation of ß-catenin signaling. WISP-3/CCN6 also suppressed ADAMTS-5 expression in C-28/I2 cells treated with cytokines. In cytokine-treated primary chondrocytes, gene silencing of WISP-3/CCN6 resulted in enhanced ADAMTS-5 expression, while MMP-10 expression was suppressed. CONCLUSION: WISP-3/CCN6 was highly expressed in end-stage OA cartilage, suggesting a role for this growth factor in cartilage homeostasis. WISP-3/CCN6-induced repression of ADAMTS-5 expression and regulation of MMP-10 expression suggest complex and context-dependent roles for WISP-3/CCN6 in cartilage biology.