Patients with atopic dermatitis (AD) have an abnormal skin barrier and are frequently colonized by S. aureus. In this study we investigated if S. aureus penetrates the epidermal barrier of subjects ...with AD and sought to understand the mechanism and functional significance of this entry. S. aureus was observed to be more abundant in the dermis of lesional skin from AD patients. Bacterial entry past the epidermis was observed in cultured human skin equivalents and in mice but was found to be increased in the skin of cathelicidin knockout and ovalbumin-sensitized filaggrin mutant mice. S. aureus penetration through the epidermis was dependent on bacterial viability and protease activity, because killed bacteria and a protease-null mutant strain of S. aureus were unable to penetrate. Entry of S. aureus directly correlated with increased expression of IL-4, IL-13, IL-22, thymic stromal lymphopoietin, and other cytokines associated with AD and with decreased expression of cathelicidin. These data illustrate how abnormalities of the epidermal barrier in AD can alter the balance of S. aureus entry into the dermis and provide an explanation for how such dermal dysbiosis results in increased inflammatory cytokines and exacerbation of disease.
African American adolescents have become more active users of digital media, which may increasingly expose them to direct online discrimination based on their racial and gender identities. Despite ...well-documented impacts of offline discrimination, our understanding of if and how direct online discrimination affects African American adolescents similarly remains limited. Guided by intersectional and ecological frameworks, we examined the association between direct online discrimination and internalized computing stereotypes in African American adolescents. Further, we explored the moderating effects of systemic and individual factors – vicarious online discrimination, parental technological attitudes, and racial identity centrality – on this association by adolescent gender. Utilizing data from 1041 African American parent-adolescent dyads, we found a positive association between adolescents’ direct online discrimination and internalized computing stereotypes. Surprisingly, greater vicarious online discrimination mitigated this association for both male and female adolescents. Further, parental technological attitudes and racial identity centrality mitigated this association only for female but not male adolescents. Our findings highlight the importance of understanding the impact of media on adolescents’ online experiences from intersectional and systemic perspectives. We discuss the implications for prospective research and educational programs focused on African American adolescents’ digital media use and online experiences.
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense ...by killing
, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against
was performed on isolates of coagulase-negative
(CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by
The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including
and
These AMPs were strain-specific, highly potent, selectively killed
, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by
These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
African Americans, especially African American women, remain one of the most underrepresented groups in technology-based degrees and careers. However, little is known about whether gender differences ...permeate African American adolescents’ engagement in technology in earlier development, such as in middle and high school (ages 12–18). Drawing on an ecological and intersectional framework, we examined if African American male and female adolescents differed in technological engagement and what contextual factors affected their engagement. We hypothesized that parental encouragement would be associated with greater technological confidence in adolescents, which would be linked to more experiences with and interests in technology. Further, we investigated if these associations would vary by adolescents’ and parents’ gender. Survey data from 1041 African American parent-adolescent dyads highlighted that adolescents had less experience and interest with technical activities than with creative activities, especially among female adolescents. More parents encouraged adolescent sons but limited daughters to use technology, yet female adolescents reported greater technological confidence. Moderated mediation analyses revealed that adolescents’ technological confidence mediated the positive association between parental encouragement and adolescents’ technological engagement across all parent-adolescent dyads, but with some nuances. Our findings suggest that prospective gender studies and educational programs should consider the influences of parenting and gender on promoting African American adolescents’ technological involvement and confidence.
Biological diversity is a key concept in the life sciences and plays a fundamental role in many ecological and evolutionary processes. Although biodiversity is inherently a hierarchical concept ...covering different levels of organization (genes, population, species, ecological communities and ecosystems), a diversity index that behaves consistently across these different levels has so far been lacking, hindering the development of truly integrative biodiversity studies. To fill this important knowledge gap, we present a unifying framework for the measurement of biodiversity across hierarchical levels of organization. Our weighted, information‐based decomposition framework is based on a Hill number of order q = 1, which weights all elements in proportion to their frequency and leads to diversity measures based on Shannon's entropy. We investigated the numerical behaviour of our approach with simulations and showed that it can accurately describe complex spatial hierarchical structures. To demonstrate the intuitive and straightforward interpretation of our diversity measures in terms of effective number of components (alleles, species, etc.), we applied the framework to a real data set on coral reef biodiversity. We expect our framework will have multiple applications covering the fields of conservation biology, community genetics and eco‐evolutionary dynamics.
Vaginal cuff dehiscence and evisceration are rare but potentially serious complications of hysterectomy. In this article, we review the incidence, risk factors, management, and preventive measures ...for dehiscence based on available literature.
Identifying risk factors for dehiscence is challenging because studies lack comparison groups and most studies are largely underpowered to draw concrete conclusions.
High-quality data on cuff dehiscence after hysterectomy are limited. Potentially modifiable risks that optimize vaginal wound healing, minimize vaginal cuff strain, and minimize cuff infection should be optimized.
Obesity is a risk factor for multiple myeloma (MM), yet results of prior studies have been mixed regarding the importance of early and/or later adult obesity; other measures of body composition have ...been less well studied.
We evaluated associations of early adult (ages 18-21) and usual adult body mass index (BMI), waist circumference, and predicted fat mass with MM by pooling data from six U.S. prospective cohort studies comprising 544,016 individuals and 2756 incident diagnoses over 20-37 years of follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations, adjusted for age and other risk factors.
Each 5 kg/m
increase in usual adult BMI was associated with a 10% increased risk of MM (HR: 1.10; 95% CI: 1.05-1.15). Positive associations were also noted for early adult BMI (HR per 5 kg/m
: 1.14; 95% CI: 1.04-1.25), height (HR per 10 cm: 1.28; 95% CI: 1.20-1.37), waist circumference (HR per 15 cm: 1.09; 95% CI: 1.00-1.19), and predicted fat mass (HR per 5 kg: 1.06; 95% CI: 1.01-1.11).
These findings highlight the importance of avoidance of overweight/obesity and excess adiposity throughout adulthood as a potential MM risk-reduction strategy.
In 2022, more than 100 000 non‐Hodgkin lymphoma (NHL) diagnoses are expected, yet few risk factors are confirmed. In this study, data from six US‐based cohorts (568 717 individuals) were used to ...examine body size and risk of NHL. Over more than 20 years of follow‐up, 11 263 NHLs were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) estimated associations with NHLs for adult body mass index (BMI), height, weight change, waist circumference and predicted fat mass. Adult height was broadly associated with NHL, but most strongly with B‐cell NHLs among non‐White participants (e.g. HRBLACK = 2.06, 95% CI: 1.62–2.62). However, the strongest association among the anthropometric traits examined was for young adult BMI and risk of diffuse large B‐cell lymphoma (DLBCL), particularly those who maintained a higher BMI into later adulthood. Individuals with BMI over 30 kg/m2 throughout adulthood had more than double the DLBCL risk (HR = 2.67, 95% CI: 1.71–4.17) compared to BMI 18.5–22.9 kg/m2. Other anthropometric traits were not associated with NHL after controlling for BMI. These results suggest that sustained high BMI is a major driver of DLBCL risk. If confirmed, we estimate that up to 23.5% of all DLBCLs (and 11.1% of all NHLs) may be prevented with avoidance of young adult obesity.
The microbiome presents great opportunities for understanding and improving the world around us and elucidating the interactions that compose it. The microbiome also poses tremendous challenges for ...mapping and manipulating the entangled networks of interactions among myriad diverse organisms. Here, we describe the opportunities, technical needs, and potential approaches to address these challenges, based on recent and upcoming advances in measurement and control at the nanoscale and beyond. These technical needs will provide the basis for advancing the largely descriptive studies of the microbiome to the theoretical and mechanistic understandings that will underpin the discipline of microbiome engineering. We anticipate that the new tools and methods developed will also be more broadly useful in environmental monitoring, medicine, forensics, and other areas.
Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, nonresponse and loss of response are common. As combination ...therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy.
Patients with pediatric Crohn’s disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12–36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected.
Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45–1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55–1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19–0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49–1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24–2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs.
Among adalimumab but not infliximab initiators, patients with pediatric Crohn’s disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. ClinicalTrials.gov, Number: NCT02772965.
Display omitted
Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, nonresponse and loss of response is common. Combination therapy with methotrexate may improve response. This randomized clinical trial compared tumor necrosis factor inhibitor combination therapy with methotrexate to tumor necrosis factor inhibitor alone. Combination therapy outperformed monotherapy for patients starting adalimumab, but not infliximab.
PDF
