Mental health inequalities during the second COVID-19 wave among Millennials who grew up in England: Evidence from the Next Steps cohort study.

BACKGROUND: There is relatively little evidence on socioeconomic inequalities in mental health among young adults after the end of the first COVID-19 wave in the UK, despite this group having faced the worse mental health and economic shocks across age groups at the start of the pandemic. METHODS: We examined differences in mental health across two points - September 2020 and February 2021 - in a cohort of 4167 Millennials aged 30-31 using life dissatisfaction, psychological distress (GHQ-12), anxiety (GAD-2), and depressive symptoms (PHQ-2). We report adjusted prevalence ratios (aPR) from random-intercept models, testing differences by educational attainment and time-varying conditions (relationship status, living arrangements with adults and children, work status, and financial changes compared with before the outbreak), adjusting for baseline covariates at ages 13-14 and health covariates at ages 25-26. RESULTS: Only dissatisfaction with life changed between time points (PR = 1.26, 95%CI 1.02-1.55). Educational attainment was not significantly associated with mental health. Being single (aPRs from 1.36 to 1.89) and being financially worse off since the start of the pandemic (aPRs from 1.58 to 1.76) were each associated with worse mental health. These associations did not further vary by educational attainment. CONCLUSION: Among Millennials who grew up in England, educational attainment was not associated with mental health whereas negative social and financial conditions were associated with worse mental health during the second COVID-19 wave. Mental health inequalities in this generation are likely to have continued increasing after the end of the first COVID-19 wave.

Parenthood and psychological distress among English Millennials during the second wave of the COVID-19 pandemic: evidence from the Next Steps cohort study.

PURPOSE: The COVID-19 pandemic led to disproportionate mental health responses in younger adults and parents. The aim of the study was to investigate how Millennial parents' experiences were associated with psychological distress over the first year of the pandemic. METHODS: We examined data in September 2020 (n men = 994; n women = 1824) and February 2021 (n men = 1054; n women = 1845) from the Next Steps cohort study (started ages 13-14 in 2003-04). In each wave, we examined differences in GHQ-12 scores between parent groups defined by the age and number of children, adjusting for background characteristics at ages 13-14, psychological distress at ages 25-26, and other circumstances during the pandemic. We also examined if differences varied by work status, financial situation before the outbreak and relationship status. RESULTS: Whereas mothers with one or two children and children aged 0-2 reported less distress than non-mothers in September 2020, there were no such differences in February 2021. Fathers with three or more children reported more distress in February 2021. Compared with non-fathers who worked, fathers were also disproportionally distressed if they were working with one child or with children aged 2 or less in September 2020. CONCLUSION: The distribution of psychological distress among Millennial parents and non-parents has varied by age, sex, parenting stage, work status and the timing of the pandemic. Generous family policies are needed, with special attention dedicated to parents combining work and family responsibilities.

Mental distress among young adults in Great Britain: long-term trends and early changes during the COVID-19 pandemic.

PURPOSE: In Great Britain, few studies documented mental health trends in young adults in the years preceding 2020, the mental health dimensions affected, and how these compare with changes observed during the COVID-19 pandemic. METHODS: Long-term trends in mental health among 16-34 year old men and women between 1991 and 2018, and changes between 2018-19 and July-September 2020 were examined using all waves from the British Household Panel Study (1991-2008), the UK Household Longitudinal Study (2009-20), and the first five UKHLS COVID-19 waves administered in April, May, June, July, and September 2020. Findings are based on the GHQ-12 continuous score (0-36), clinically significant cases (4 + /12) and severe cases (7 + /12) for mental distress, and item endorsements. RESULTS: Between 1991 and 2018, the prevalence of cases (4 + /12) increased from 14-22% to 19-32% across groups. Increases were largest in women aged 16-24. In April 2020, the risk of caseness (4 + /12) increased across groups by 55% to 80% compared to the 2018-19 baseline. This increase, however, rapidly diminished over time: in July-September 2020, there was only a higher risk of caseness (4 + /12) in men aged 25-34 (prevalence ratio = 1.29, 95% CI 1.01-1.65) compared to the 2018-19 baseline. CONCLUSION: Whereas distress surged in April 2020, its return to pre-pandemic levels by September 2020 highlights the nuanced impact that the pandemic may have over time. Given the magnitude of the decline in mental health over the past decade, attention must be given to young adults once the pandemic ends.

Transition milestones and life satisfaction at ages 25/26 among cohorts born in 1970 and 1989-90.

The transition to adulthood has become more prolonged, complex, and risk-laden over the past two decades. These changes may contribute to the decline in wellbeing observed among young adults. We test the role of reaching different transition milestones on life satisfaction by ages 25-26 among men and women born 20 years apart in 1970 and 1989-90, using data from the 1970 British Cohort (men n = 3764, women n = 4568) and Next Steps (men n = 3246, women n = 4281) studies. We regressed life satisfaction on education, housing tenure, cohabitation with parents, economic activity, relationship status, and parenthood, and tested the role of changes in the prevalence and association of milestones in explaining cohort differences in life satisfaction using decomposition analyses. Home ownership, full-time employment, cohabitation with a partner, and marriage were robust predictors of life satisfaction in both cohorts. Comparing cohorts, the association of milestones with life satisfaction was stable among men but differed among women: in the later-born cohort, women no longer benefitted from higher education and further suffered from not being in full-time employment. The findings shed new light on the relationships between young adult transitions and life satisfaction during the third decade of life. These support the argument that decreases in wellbeing may be driven by changes in the prevalence and meaning of these milestones over time, particularly among women.

Has the distribution of smoking across young adult transition milestones changed over the past 20 years? Evidence from the 1970 British Cohort Study (1996) and Next Steps (2015-16).

INTRODUCTION: Transitions into work and family life during young adulthood exacerbate differences in the progression of smoking over the life-course. Few have considered how changes in smoking and the transition to adulthood in the past two decades have influenced these relationships over time. METHODS: We compared the distribution of smoking at ages 25-26 across transition milestones among 3764 men and 4568 women in the 1970 British Cohort study (1996) and 3426 men and 4281 women in the Next Steps study (2015-16). We regressed occasional and daily smoking status on educational attainment, economic activity, living arrangements, relationship status, and parenthood, adjusting for family background, socio-demographics, and smoking history. RESULTS: There were few differences in associations between the 1996 and 2015-16 samples. Young men and women were less likely to smoke if they had higher education, were homeowners, and cohabited with a partner. Women were less likely to smoke occasionally if they were full-time students, and men were less likely to smoke daily if they were employed full-time and not living with children. However, comparing associations in 2015-16 to 1996: 1) in men, higher education had a weaker negative association and living with a partner had a stronger negative association with daily smoking; 2) in women, independently renting had a weaker positive association with daily smoking. CONCLUSIONS: Despite considerable changes in smoking and the transition to adulthood over the past two decades, the distribution of smoking at ages 25-26 across transition milestones has been relatively stable during this time period in Great Britain.

[Socioeconomic profile and smoking among adolescents in vocational training]. / Profil socioéconomique et tabagisme chez les adolescents en centre de formation des apprentis.

BACKGROUND: Targeted interventions among vulnerable youth populations represent an important approach to the reduction of health inequalities. We must, however, ensure that impacts are not unequally distributed according to the range of resources available to them. We explore these concerns among youth in vocational training to be enrolled in a smoking cessation intervention by describing (1) their socio-economic profile and (2) the association between their socioeconomic characteristics, their smoking practices, and key factors that could be targeted in interventions. METHODS: A total of 234 young people aged 15-20 years were recruited in three centers in the Lorraine region in France in 2016-2017 as part of the Social Network and Tobacco Cessation (Réseau social et sevrage tabagique [RESIST]) study. We measured participants' socio-economic characteristics using their parents' education and occupational grade. We examined the associations of these characteristics with participants' smoking habits, intention to quit, nicotine dependence, presence of smokers in their network, and representation of a young smoker. We examined the associations between variables with bivariate tests depending on the nature of the variables. RESULTS: Participants were more likely to be from a socio-professional background more modest than the national average (56% versus 33%), but still exhibited considerable socioeconomic variability. Smoking status did not vary significantly according to the educational level of the participants' parents (from 52% to 57%, P=0.78) or occupational grade (from 52% to 58%, P=0.35). Compared to participants whose parents had completed a professional or pre-university degree, participants with parents in the lowest education category were less likely to report not intending to quit (P=0.01) and more likely to report seriously considering to quit in the next six months (P=0.03) and to have already tried to quit but failed (P=0.01). CONCLUSION: It is tempting to define youth in vocational training as a homogeneous group, especially when they share the same school environment, employment status, and income. Our results, however, highlight substantial variability in their socioeconomic profiles and smoking characteristics. Researchers are encouraged to further consider these equity issues to contribute to the reduction of health inequalities.

Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss.

Targeted disruption of the histidine decarboxylase gene (HDC(-/-)), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC(-/-) mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC(-/-) mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1alpha-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-kappaB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC(-/-) mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption.

Enhanced proliferation and differentiation of human articular chondrocytes when seeded at low cell densities in alginate in vitro.

Dedifferentiated human articular chondrocytes exhibited a wide variation in their capacity to proliferate and redifferentiate in an alginate suspension culture system. The greatest extent of proliferation and redifferentiation was seen to be dependent on the formation of clonal populations of chondrocytes and correlated inversely with the initial cell seeding density. Redifferentiating chondrocytes seeded at low density (1 x 10(4) cells/ml alginate) compared with chondrocytes that were seeded at high density (1 x 10(6) cells/ml alginate) showed a nearly 3-fold higher median increase in cell number. a 19-fold greater level of type-II collagen mRNA expression, a 4-fold greater level of aggrecan mRNA expression, and a 6-fold greater level of sulfated glycosaminoglycan deposition at 4 weeks of culture. Matrix molecules from low-density cultures were assembled into chondrocyte-encapsulated, spherical extracellular matrices that were readily visualized in sections from 12-week cultures stained with antibodies against types I and II collagen and aggrecan. Ultrastructural analysis of 12-week low-density cultures confirmed the presence of thin collagen fibrils throughout the matrix.

Healing of chondral and osteochondral defects in a canine model: the role of cultured chondrocytes in regeneration of articular cartilage.

In this study a canine model was developed to investigate the nature of early healing responses to both chondral and osteochondral defects and to evaluate the tissue regenerative capacity of cultured autologous chondrocytes in chondral defects. The healing response to surgically created chondral defects was minor, with little cellular infiltration. In contrast, osteochondral defects exhibited a rapid cellular response, resulting ultimately in the formation of fibrous tissue. The lack of significant cellular activity in chondral defects suggests that an evaluation of the capacity of cultured autologous chondrocytes to regenerate articular cartilage is best studied in chondral defects using the canine model. When dedifferentiated cultured articular chondrocytes were implanted into chondral defects, islands of type II collagen staining were demonstrated in the regenerative tissue within 6 weeks. The relatively early expression of cartilage specific markers by the implanted chondrocytes, coupled with the inability of untreated chondral defects to repair or regenerate, demonstrates the utility of the canine model in evaluating novel materials for cartilage repair and regeneration.

Targeted overexpression of transforming growth factor alpha in the epidermis of transgenic mice elicits hyperplasia, hyperkeratosis, and spontaneous, squamous papillomas.

To assess the effects of transforming growth factor alpha (TGF-alpha) on mammalian skin in vivo, we have targeted its expression to the epidermis of transgenic mice using a vector based on the human K1 (HK1) gene. Neonatal mice expressing the HK1.TGF-alpha transgene were often smaller than normal littermates and had precocious eyelid opening and wrinkled, scaly skin with diffuse alopecia. Juvenile transgenic mouse epidermis was uniformly hyperkeratotic, but this pattern was generally less pronounced in adult transgenic mice unless they expressed high levels of the HK1.TGF-alpha transgene. Spontaneous, squamous papillomas occurred at sites of wounding in adult mice expressing high levels of HK1.TGF-alpha; however, most were prone to regression. Immunoreactive TGF-alpha was 2-6 times higher in the epidermis of these HK1.TGF-alpha lines. Immunoreactive epidermal growth factor receptor had a normal pattern of expression in nonphenotypic adult epidermis, but a marked reduction in the receptor population was detected in hyperplastic newborn epidermis and phenotypic adult epidermis. Autoradiographic localization of 125I-epidermal growth factor showed a similar pattern of distribution, suggesting that the sites of increased TGF-alpha expression induced epidermal growth factor receptor down-regulation. These data demonstrate the in vivo effect of deregulated TGF-alpha expression on epidermal proliferation and differentiation and suggest a potential role for TGF-alpha in carcinogenesis and other hyperproliferative epidermal disorders.

Identification of a calcium-inducible, epidermal-specific regulatory element in the 3'-flanking region of the human keratin 1 gene.

Previous studies have shown that the process of epidermal differentiation is profoundly influenced by the level of intracellular calcium within keratinocytes. In this study we have identified a 249-bp region, located 7.9 kb downstream from the promoter of the human keratin 1 (HK1) gene, that is able to activate a SV40 minimal promoter chloramphenicol acetyl transferase (CAT) construct in transfected murine keratinocytes. This activity was potentiated by increased levels of calcium and was independent of the position and orientation of the 249-bp fragment. The 249-bp fragment demonstrated a marked specificity for epidermal keratinocytes and was not active in fibroblasts or in a breast epithelial cell line. Moreover, this fragment could activate CAT expression in a construct driven by the HK1 promoter, which alone had no intrinsic CAT activity. A 102-bp fragment derived from the 249-bp fragment was still responsive to calcium but no longer retained cell-type specificity. An AP-1 site at position +7903 and encoded by both the 249-bp and 102-bp fragments is implicated as the cis-element that mediates the calcium response. Taken collectively, these data identify and characterize a regulatory element that is able to activate both heterologous or homologous promoters in response to increased levels of intracellular calcium in keratinocytes.

Hyperplasia, hyperkeratosis and benign tumor production in transgenic mice by a targeted v-fos oncogene suggest a role for fos in epidermal differentiation and neoplasia.

A vector, derived from the human K1 keratin gene, has been employed to target v-fos expression exclusively in the epidermis of transgenic mice. Adult transgenic mice expressors (3-4 months) displayed hyperplasia and hyperkeratosis, initially in wounded (tagged) ears, which later became bilateral. This phenotype appeared at other epidermal sites, most notably in the axilla and inguinal areas. This indicates that a second promoting event, such as wounding or friction, is required to elicit these pathological changes. Highly keratotic benign ear lesions and benign squamous papillomas appeared after long latency at sites of phenotypic epidermis. These data suggest that v-fos may be interfering with c-fos function in normal keratinocyte differentiation, but by itself is insufficient to elicit overt benign lesions.

Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogene.

The regulatory elements of the human keratin K1 gene have been used to target expression of the v-Ha-ras oncogene exclusively in the epidermis of transgenic mice. We developed 12 transgenic mouse lines that express the HK1.ras transgene, producing epidermal hyperplasia in neonates and hyperkeratosis in juveniles. Eventually this skin phenotype diminished but with time adult animals developed papillomas that could persist or regress. The rate and frequency of tumorigenesis appeared to be limited, which suggests that v-Ha-ras requires a second or even third event to elicit and maintain a benign phenotype in transgenic mice. Since in certain transgenic lines papillomas appeared at wound sites, it appears that the promotion stimulus from wounding may be a second event. We envision that such transgenic mice that express v-Ha-ras in the epidermis will become a powerful model for assessing how environmental and molecular factors affect the process of multistage skin carcinogenesis in vivo, as well as a model for evaluating novel therapeutic protocols.

Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis.

Epidermolytic hyperkeratosis is a hereditary skin disorder characterized by blistering and a marked thickening of the stratum corneum. In one family, affected individuals exhibited a mutation in the highly conserved carboxyl terminal of the rod domain of keratin 1. In two other families, affected individuals had mutations in the highly conserved amino terminal of the rod domain of keratin 10. Structural analysis of these mutations predicts that heterodimer formation would be unaffected, although filament assembly and elongation would be severely compromised. These data imply that an intact keratin intermediate filament network is required for the maintenance of both cellular and tissue integrity.