The Controversies of Deaccession in Museums: The Pre-Columbian Collection at the University of Texas at Austin

Examination of the legal, ethical, and social context and implications of deaccession in museums. Case study on the orphaned pre-Columbian collection at the University of Texas at Austin, deaccessioned from the Texas Memorial Museum.Art and Art Histor

Matrigel modulates a stem cell phenotype and promotes tumor cell formation in a mantle cell lymphoma cell line

Tumors may be maintained by subpopulations of cells possessing stem cell-like properties. We evaluated the stem cell-like and tumor-forming properties of side population (SP) and CD133+/ CD44+ cells in Granta 519, a human mantle cell lymphoma cell line. The in-vitro Cobblestone Area Forming Cell (CAFC) assay, designed to detect stem and progenitor cells, revealed that SP cells contained the greatest proportion of stem cell-like cells. The addition of Matrigel to CAFC assays of SP and non-SP cells both increased their respective stem cell frequencies in comparison to those cultures without Matrigel, and additionally resulted in observed stem cell frequencies which were the same between SP and non-SP cells. Contrary, Matrigel decreased the stem cell frequencies of CD133+/CD44+ or CD133-/CD44- cells. In-vivo assays revealed tumor formation from Matrigel-mixed SP and non-SP cells, and in one instance, occurred with as few as one Matrigel-mixed SP cell. Vehicle-mixed injections of SP and non-SP tumor cells resulted in tumor formation from SP cells only. Tumor formation did not occur from Matrigel nor hyaluronan (cellular substrate for CD44-expressing cells)-mixed populations of CD133+/CD44+ or CD133-/CD44- cells. These data demonstrate that Matrigel modulates a stem cell phenotype and promotes tumor formation from SP and non-SP cells. The tumor micro-environmental niche and tumor cell to micro-environmental interactions may be important future targets for novel chemotherapeutic agent

The relationships between women’s reproductive factors:a Mendelian randomisation analysis

BACKGROUND: Women’s reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors. METHODS: We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap. RESULTS: LDSC indicated that most reproductive factors are genetically correlated (r(g) range: |0.06–0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (r(g) < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = −0.38 SD, CI = −0.44, −0.32). CONCLUSION: This study presents evidence that women’s reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman’s entire reproductive history, including the causal interplay between reproductive factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02293-5

The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities

International audienceSince the beginning of the COVID-19 pandemic, discussions on social media and blogs have indicated that women have experienced menstrual changes, including altered menstrual duration, frequency, regularity, and volume (heavier bleeding and clotting), increased dysmenorrhea, and worsened premenstrual syndrome. There have been a small number of scientific studies of variable quality reporting on menstrual cycle features during the pandemic, but it is still unclear whether apparent changes are due to COVID-19 infection/illness itself, or other pandemic-related factors like increased psychological stress and changes in health behaviours. It is also unclear to what degree current findings are explained by reporting bias, recall bias, selection bias and confounding factors. Further research is urgently needed. We provide a list of outstanding research questions and potential approaches to address them. Findings can inform policies to mitigate against gender inequalities in health and society, allowing us to build back better post-COVID

Language processing skills linked to FMR1 variation: A study of gaze-language coordination during rapid automatized naming among women with the FMR1 premutation

This work is licensed under a Creative Commons Attribution 4.0 International License.The FMR1 premutation (PM) is relatively common in the general population. Evidence suggests that PM carriers may exhibit subtle differences in specific cognitive and language abilities. This study examined potential mechanisms underlying such differences through the study of gaze and language coordination during a language processing task (rapid automatized naming; RAN) among female carriers of the FMR1 PM. RAN taps a complex set of underlying neuropsychological mechanisms, with breakdowns implicating processing disruptions in fundamental skills that support higher order language and executive functions, making RAN (and analysis of gaze/language coordination during RAN) a potentially powerful paradigm for revealing the phenotypic expression of the FMR1 PM. Forty-eight PM carriers and 56 controls completed RAN on an eye tracker, where they serially named arrays of numbers, letters, colors, and objects. Findings revealed a pattern of inefficient language processing in the PM group, including a greater number of eye fixations (namely, visual regressions) and reduced eye-voice span (i.e., the eyes’ lead over the voice) relative to controls. Differences were driven by performance in the latter half of the RAN arrays, when working memory and processing load are the greatest, implicating executive skills. RAN deficits were associated with broader social-communicative difficulties among PM carriers, and with FMR1-related molecular genetic variation (higher CGG repeat length, lower activation ratio, and increased levels of the fragile X mental retardation protein; FMRP). Findings contribute to an understanding of the neurocognitive profile of PM carriers and indicate specific gene-behavior associations that implicate the role of the FMR1 gene in language-related processes.NIH R01DC010191NIH R01MH091131NIH P30 HD0311

DNA methylation and body mass index:investigating identified methylation sites at HIF3A in a causal framework

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation.Rebecca C. Richmond, Gemma C. Sharp, Mary E. Ward, Abigail Fraser, Oliver Lyttleton, Wendy L. McArdle, Susan M. Ring, Tom R. Gaunt, Debbie A. Lawlor, George Davey Smith, and Caroline L. Relto

Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells.

Huntington's disease is a neurodegenerative disorder caused by CAG expansion that results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt with polyglutamine expansion is proapoptotic in different cell types. Here, we show that caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3 cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to cleavable htt, caspase-resistant htt with an expanded polyglutamine tract has reduced toxicity in apoptotically stressed neuronal and nonneuronal cells and forms aggregates at a much reduced frequency. These results suggest that inhibiting caspase cleavage of htt may therefore be of potential therapeutic benefit in Huntington's disease

Stigma experiences, effects and coping among individuals affected by Buruli ulcer and yaws in Ghana.

BACKGROUND: Stigma related to skin neglected tropical diseases like Buruli ulcer (BU) and yaws has remained underexplored and existing studies are limited to individual diseases despite the WHO call for integration in disease management. Within two districts in central Ghana, we explored stigma associated with BU and yaws to understand overlaps and disease-specific nuances to help guide integrated interventions. METHODOLOGY/PRINCIPAL FINDINGS: In-depth interviews were conducted with 31 current or formerly affected individuals to assess the experiences, effects and coping strategies adopted to manage disease related stigma. Data were analysed along broad themes based on the sociological construct of macro and micro interaction and Goffman's treatise on stigma. Disapproving community labels fueled by misconceptions were noted among BU participants which contributed to macro stigma experiences, including exclusion, discrimination and avoidance. In contrast, a high level of social acceptance was reported among yaws participants although some micro-level stigma (anticipated, felt and self-stigma) were noted by individuals with both diseases. While younger participants experienced name-calling and use of derogatory words to address affected body parts, older participants and caregivers discussed the pain of public staring. Stigma experiences had negative consequences on psychosocial well-being, schooling, and social relations, particularly for BU affected people. Problem-focused strategies including confrontation, selective disclosure and concealment as well as emotion-focused strategies (religious coping and self-isolation) were noted. CONCLUSIONS AND SIGNIFICANCE: The types and levels of stigma varied for BU and yaws. Stigma experiences also differed for adults and children in this setting and these differences should be accounted for in integrated interventions for these skin NTDs. School health programs need to prioritize educating school teachers about skin NTDs and the negative impact of stigma on the wellbeing of children

Buruli-RifDACC: Evaluation of the efficacy and cost-effectiveness of high-dose versus standard-dose rifampicin on outcomes in Mycobacterium ulcerans disease, a protocol for a randomised controlled trial in Ghana.

Background: Buruli ulcer (BU) can lead to disfiguring ulcers and permanent disability. The 2030 World Health Organization (WHO) road map for Neglected Tropical Diseases (NTDs) calls for major scaling up in diagnosis and management to eliminate disability due to the disease. Current treatment for BU is with daily oral rifampicin (10mg/kg dose) and clarithromycin (15mg/kg dose) for eight weeks, combined with standard gauze wound dressings. Dialkylcarbamoyl chloride (DACC)-coated dressings have been shown to irreversibly bind bacteria on wound surfaces resulting in their removal when dressings are changed. This trial aims to determine whether combining a high-dose oral rifampicin regimen with DACC dressings can improve the rate of wound healing relative to standard-dose oral rifampicin combined with DACC dressings. Methods: This is an individual, multi-centre Phase 3 randomised controlled trial, which will be conducted in three clinical sites in Ghana. The primary outcome measure will be the mean time to clearance of viable mycobacteria. Cost and health-related quality of life data will be collected, and a cost-effectiveness analysis will be performed. Discussion: The findings from this trial could lead to a change in how BU is treated. A shorter but more efficacious regimen would lead to improved treatment outcomes and potentially substantial financial and economic savings. Trial registration: Pan African Clinical Trials Repository (registration number; PACTR202011867644311). Registered on 30th November 2020

Protocol for a randomised controlled trial of a school based cognitive behaviour therapy (CBT) intervention to prevent depression in high risk adolescents (PROMISE)

<p>Abstract</p> <p>Background</p> <p>Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood. Relatively few adolescents with depression are identified and referred for treatment indicating the need to investigate alternative preventive approaches.</p> <p>Study Design</p> <p>A pragmatic cluster randomised controlled trial evaluating the effectiveness of a school based prevention programme on symptoms of depression in "high risk" adolescents (aged 12-16). The unit of allocation is year groups (n = 28) which are assigned to one of three conditions: an active intervention based upon cognitive behaviour therapy, attention control or treatment as usual. Assessments will be undertaken at screening, baseline, 6 months and 12 months. The primary outcome measure is change on the Short Mood and Feeling Questionnaire at 12 months. Secondary outcome measures will assess changes in negative thoughts, self esteem, anxiety, school connectedness, peer attachment, alcohol and substance misuse, bullying and self harm.</p> <p>Discussion</p> <p>As of August 2010, all 28 year groups (n = 5023) had been recruited and the assigned interventions delivered. Final 12 month assessments are scheduled to be completed by March 2011.</p> <p>Trial Registration</p> <p>ISRCTN19083628</p