Measurement of social norms for entertainment-education.

BACKGROUND: While there has been a marked increase in measurement and scholarship surrounding social norms in recent years, there is little evidence related to social norms measurement in the context of health campaigns utilizing entertainment-education. Entertainment-education goals and objectives have shifted over time to include social norms and an update is needed to merge contemporary practice with the most recent measures from the literature. The aim of the present study was to analyze commonly used quantitative measures and their properties for social norms and entertainment-education, specifically on the topic of family planning, to bolster ongoing research and practice efforts by validating items for social norms measurement in entertainment-education programs. METHODS: The study used data from a survey conducted with 438 married women aged 19-34 in the Central Province of Zambia in 2019 who were exposed to the entertainment-education initiative Kwishilya (Over the Horizon), a Bemba-language, 156-episode radio program designed to shift social norms on family planning. Multiple items were included to measure descriptive norms, injunctive norms, and outcome expectations. Exploratory factor analysis and estimates of scale reliability were conducted to understand the properties and structure of the social norms items. RESULTS: Results showed a five-factor solution best fit the data, which accounted for 45.7% of the variance, exhibited fair reliability, and loaded largely as expected. CONCLUSIONS: This study provides a useful tool for practitioners and scholars to use globally to measure important social norms constructs in entertainment-education.

What Works to Address Violence Against Children (VAC) in and Around Schools.

Violence against children (VAC) is a pervasive, global issue with both short- and long-term health, social, and economic consequences. This systematic review sought to identify best practices for designing and implementing social and behavior change communication (SBCC) programs targeting VAC in and around schools. Combinations of key search terms within five domains were entered into four databases: PubMed Central, Google Scholar, Sociological Abstracts, and EBSCOhost. Results were screened according to the inclusion and exclusion criteria. Namely, articles had to be published in English, be published after March 2014, focus on VAC in and around schools, focus on children, and use SBCC approaches. The searches produced 892,271 results. Of these, 63,183 were screened and 54 articles were selected. These articles were combined with 16 articles, gathered from a previous systematic review using the same databases and search domains conducted by the same research team, for a total of 70 articles. Articles were quantitatively analyzed using a coding guide in STATA and qualitatively analyzed using Nvivo. Results showed that most programs addressed bullying, were implemented in high-income countries, and included children aged 10 and older. Best practices in program design were using theory, conducting formative research, and involving program beneficiaries. Best practices in implementation were combining whole-school and targeted approaches, including special and hidden populations, involving secondary and tertiary audiences, using nonclassroom settings, using peer leader/mentor and cascade training models, and conducting process monitoring. Implications and avenues for future planning and implementation of SBCC interventions to address VAC in and around schools are discussed.

Menstrual management among adolescent girls in Uttar Pradesh, India: An examination of interpersonal and mediated communication as delivery mechanisms for practical guidance.

Background: Adolescent girls' right to achieve menstrual health and hygiene management (MHHM) healthfully is yet to be realized. One reason is the lack of practical guidance on the procurement, use, and disposal of menstrual products. This study defined interpersonal practical guidance (IPG) as face-to-face communication and mediated practical guidance (MPG) as social and behavior change communication (SBCC) intervention-driven communications through print and media materials. We examine the impact of these two delivery mechanisms of practical guidance on adolescent MHHM knowledge, attitudes, and practices (KAP) following an SBCC intervention in India. Objectives: To understand how IPG and SBCC-driven MPG independently influence adolescent girls' KAP on the procurement, use, and disposal of menstrual products and whether those who receive both IPG and MPG have better KAP related to the procurement, use, and disposal of menstrual cloth or sanitary pads than those who receive only one form of practical guidance or none at all. Methods: Adolescent girls' questionnaire responses from GARIMA's case-comparison evaluation were analyzed using Stata/SE 17 (n = 2,384). Girls were matched on sociodemographic and socioeconomic variables. χ 2 analysis examined relationships between sociodemographic, practical guidance, and KAP variables. Multivariate logistic regression assessed associations between practical guidance and KAP variables. Results: There are significant associations between adolescent girls' KAP depending on whether they received IPG, SBCC-driven MPG, or both. IPG and MPG delivered together has greater odds of predicting correct menstrual management KAP than when delivered separately. These effects were most notable for adolescent girls' knowledge and practices related to using and disposing of menstrual hygiene products. Conclusion: There is urgent need to create positive, sustainable changes to address menstrual health and hygiene management. This study introduces an innovative approach that utilizes interpersonal and mediated communication as mechanisms to deliver practical guidance on menstrual management. Future interventions should implement and evaluate to better understand the role of practical guidance in ensuring all women and girls are prepared to confidently manage their menstrual health.

A Systematic Review of Menstrual Health and Hygiene Management (MHHM) as a Human Right for Adolescents Girls.

Despite its relationship with several development issues and sexual health, menstrual health and hygiene management among adolescents have until recently been ignored by practitioners and researchers. This paper is a systematic review of existing literature and argues that menstrual health and hygiene management is a human rights issue. 28,745 articles were screened, with 84 articles included in the full-text review and quality assessment. The results indicate that using a cross-cutting, human rights framework to address inadequate menstrual health and hygiene management is fundamental to promoting menstrual health and hygiene management with dignity among girls and women across the globe.

Damage-induced chromatome dynamics link Ubiquitin ligase and proteasome recruitment to histone loss and efficient DNA repair.

Eukaryotic cells package their genomes around histone octamers. In response to DNA damage, checkpoint activation in yeast induces core histone degradation resulting in 20%-40% reduction in nucleosome occupancy. To gain insight into this process, we developed a new approach to analyze the chromatin-associated proteome comprehensively before and after damage. This revealed extensive changes in protein composition after Zeocin-induced damage. First, core histones and the H1 homolog Hho1 were partially lost from chromatin along with replication, transcription, and chromatin remodeling machineries, while ubiquitin ligases and the proteasome were recruited. We found that the checkpoint- and INO80C-dependent recruitment of five ubiquitin-conjugating factors (Rad6, Bre1, Pep5, Ufd4, and Rsp5) contributes to core and linker histone depletion, reducing chromatin compaction and enhancing DNA locus mobility. Importantly, loss of Rad6/Bre1, Ufd4/TRIP12, and Pep5/VPS11 compromise DNA strand invasion kinetics during homology-driven repair. Thus we provide a comprehensive overview of a functionally relevant genome-wide chromatin response to DNA damage.

Dimensions of Misinformation About the HPV Vaccine on Instagram: Content and Network Analysis of Social Media Characteristics.

BACKGROUND: The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram. OBJECTIVE: The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine network. METHODS: From April 2018 to December 2018, we collected publicly available English-language Instagram posts containing hashtags #HPV, #HPVVaccine, or #Gardasil using Netlytic software (n=16,607). We randomly selected 10% of the sample and content analyzed relevant posts (n=580) for text, image, and social media features as well as holistic attributes (eg, sentiments, personal stories). Among antivaccine posts, we organized elements of misinformation within four broad dimensions: 1) misinformation theoretical domains, 2) vaccine debate topics, 3) evidence base, and 4) health beliefs. We conducted univariate, bivariate, and network analyses on the subsample of posts to quantify the role and position of individual posts in the network. RESULTS: Compared to provaccine posts (324/580, 55.9%), antivaccine posts (256/580, 44.1%) were more likely to originate from individuals (64.1% antivaccine vs 25.0% provaccine; P<.001) and include personal narratives (37.1% vs 25.6%; P=.003). In the antivaccine network, core misinformation characteristics included mentioning #Gardasil, purporting to reveal a lie (ie, concealment), conspiracy theories, unsubstantiated claims, and risk of vaccine injury. Information/resource posts clustered around misinformation domains including falsification, nanopublications, and vaccine-preventable disease, whereas personal narrative posts clustered around different domains of misinformation, including concealment, injury, and conspiracy theories. The most liked post (6634 likes) in our full subsample was a positive personal narrative post, created by a non-health individual; the most liked post (5604 likes) in our antivaccine subsample was an informational post created by a health individual. CONCLUSIONS: Identifying characteristics of misinformation related to HPV vaccine on social media will inform targeted interventions (eg, network opinion leaders) and help sow corrective information and stories tailored to different falsehoods.

Using Social Media to Communicate Sustainable Preventive Measures and Curtail Misinformation.

Effective crisis and risk communication strategies are crucial to promote preventive measures, particularly during times of emergency such as the global SARS-CoV-2 (COVID-19) pandemic. With its global reach, social media is a key source of news and information about COVID-19. However, the abundance of misinformation about personal protective measures that people post on social media, makes it imperative to develop a deeper understanding of effective messaging strategies. Improving the quality of information and strategy with which it is disseminated through social media is crucial to minimizing anxiety, panic and improving the adoption of sustainable preventive measures in addition to curtailing misinformation. Understanding the components of effective health communication strategies allows us to glean common methods to address misinformation which in turn lead to people adopting the appropriate preventive measures. The purpose of this article is to understand how effective social media communication strategies can be crafted to promote sustainable preventive measures and curtail wide-spread misinformation. Health organizations as well as communications organizations have made available information for effective social media messaging and more importantly serve as a gateway to other resources. We review their recommendations to identify common social media communication elements on the adoption of sustainable preventive measures and effective strategies for curtailing misinformation. We further review social media messaging during the Ebola and Zika outbreaks to evaluate the success of social media strategies and draw from lessons learned. We then create a set of best practices for developing and disseminating social media messaging regarding COVID-19.

Loss of an H3K9me anchor rescues laminopathy-linked changes in nuclear organization and muscle function in an Emery-Dreifuss muscular dystrophy model.

Mutations in the nuclear structural protein lamin A produce rare, tissue-specific diseases called laminopathies. The introduction of a human Emery-Dreifuss muscular dystrophy (EDMD)-inducing mutation into the C. elegans lamin (LMN-Y59C), recapitulates many muscular dystrophy phenotypes, and correlates with hyper-sequestration of a heterochromatic array at the nuclear periphery in muscle cells. Using muscle-specific emerin Dam-ID in worms, we monitored the effects of the mutation on endogenous chromatin. An increased contact with the nuclear periphery along chromosome arms, and an enhanced release of chromosomal centers, coincided with the disease phenotypes of reduced locomotion and compromised sarcomere integrity. The coupling of the LMN-Y59C mutation with the ablation of CEC-4, a chromodomain protein that anchors H3K9-methylated chromatin at the nuclear envelope (NE), suppressed the muscle-associated disease phenotypes. Deletion of cec-4 also rescued LMN-Y59C-linked alterations in chromatin organization and some changes in transcription. Sequences that changed position in the LMN-Y59C mutant, are enriched for E2F (EFL-2)-binding sites, consistent with previous studies suggesting that altered Rb-E2F interaction with lamin A may contribute to muscle dysfunction. In summary, we were able to counteract the dominant muscle-specific defects provoked by LMNA mutation by the ablation of a lamin-associated H3K9me anchor, suggesting a novel therapeutic pathway for EDMD.

Characterizing HPV Vaccine Sentiments and Content on Instagram.

Background. With its growing popularity, inclusion of image and text, and user-friendly interface, Instagram is uniquely positioned for exploring health behaviors and sources and types of informational exposure related to the human papillomavirus (HPV) vaccine. Aims. To characterize public Instagram posts about the HPV vaccine and quantify the impact of sentiment and context on engagement via likes. Method. Using Netlytic, 3,378 publicly available English-language posts were collected using the search terms "#HPV," "#HPVVaccine," and "#Gardasil." We randomly selected 1,200 posts to content analyze. Our final analytic sample included 360 posts after excluding posts whose links were no longer active (n = 221) or that were not relevant (n = 619). Results. A higher proportion of posts were pro-vaccine (55.8%) than anti-vaccine (42.2%). Pro-HPV vaccination posts were liked significantly less than anti-vaccination posts (24 vs. 86 likes; p < .001). More posts contained actionable information/resources (63.9%) than personal narrative elements (36.1%). Less than one in three posts (30.0%) came from health-related sources. Discussion. Pro-vaccine posts were more prevalent on Instagram, and anti-vaccine posts had higher engagement and typically included misleading information about the HPV vaccine. Personal narratives skewed toward anti-vaccine sentiments and most were produced by individual users. Pro-vaccine narratives portrayed individuals who received the vaccine, but provided limited details on vaccine experiences, starkly contrasting with the depth of details in anti-vaccine personal narrative posts. Conclusion. On Instagram, individuals and organizations have an opportunity to promote HPV vaccination by continuing to provide informational resources in addition to creating more narrative-style posts.

Chromosome Dynamics in Response to DNA Damage.

Recent advances in both the technologies used to measure chromatin movement and the biophysical analysis used to model them have yielded a fuller understanding of chromatin dynamics and the polymer structure that underlies it. Changes in nucleosome packing, checkpoint kinase activation, the cell cycle, chromosomal tethers, and external forces acting on nuclei in response to external and internal stimuli can alter the basal mobility of DNA in interphase nuclei of yeast or mammalian cells. Although chromatin movement is assumed to be necessary for many DNA-based processes, including gene activation by distal enhancer-promoter interaction or sequence-based homology searches during double-strand break repair, experimental evidence supporting an essential role in these activities is sparse. Nonetheless, high-resolution tracking of chromatin dynamics has led to instructive models of the higher-order folding and flexibility of the chromatin polymer. Key regulators of chromatin motion in physiological conditions or after damage induction are reviewed here.

Chromatin and nucleosome dynamics in DNA damage and repair.

Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin structure and its dynamic changes in response to genotoxic stress, focusing on both subnuclear organization and the physical mobility of DNA. We review the requirements and mechanisms that cause chromatin relocation, enhanced mobility, and chromatin unfolding as a consequence of genotoxic lesions. An intriguing link has been established recently between enhanced chromatin dynamics and histone loss.

Two loci single particle trajectories analysis: constructing a first passage time statistics of local chromatin exploration.

Stochastic single particle trajectories are used to explore the local chromatin organization. We present here a statistical analysis of the first contact time distributions between two tagged loci recorded experimentally. First, we extract the association and dissociation times from data for various genomic distances between loci, and we show that the looping time occurs in confined nanometer regions. Second, we characterize the looping time distribution for two loci in the presence of multiple DNA damages. Finally, we construct a polymer model, that accounts for the local chromatin organization before and after a double-stranded DNA break (DSB), to estimate the level of chromatin decompaction. This novel passage time statistics method allows extracting transient dynamic at scales varying from one to few hundreds of nanometers, it predicts the local changes in the number of binding molecules following DSB and can be used to characterize the local dynamic of the chromatin.

Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates.

Nucleosomes are essential for proper chromatin organization and the maintenance of genome integrity. Histones are post-translationally modified and often evicted at sites of DNA breaks, facilitating the recruitment of repair factors. Whether such chromatin changes are localized or genome-wide is debated. Here we show that cellular levels of histones drop 20-40% in response to DNA damage. This histone loss occurs from chromatin, is proteasome-mediated and requires both the DNA damage checkpoint and the INO80 nucleosome remodeler. We confirmed reductions in histone levels by stable isotope labeling of amino acids in cell culture (SILAC)-based mass spectrometry, genome-wide nucleosome mapping and fluorescence microscopy. Chromatin decompaction and increased fiber flexibility accompanied histone degradation, both in response to DNA damage and after artificial reduction of histone levels. As a result, recombination rates and DNA-repair focus turnover were enhanced. Thus, we propose that a generalized reduction in nucleosome occupancy is an integral part of the DNA damage response in yeast that provides mechanisms for enhanced chromatin mobility and homology search.

Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos.

Interphase chromatin is organized in distinct nuclear sub-compartments, reflecting its degree of compaction and transcriptional status. In Caenorhabditis elegans embryos, H3K9 methylation is necessary to silence and to anchor repeat-rich heterochromatin at the nuclear periphery. In a screen for perinuclear anchors of heterochromatin, we identified a previously uncharacterized C. elegans chromodomain protein, CEC-4. CEC-4 binds preferentially mono-, di-, or tri-methylated H3K9 and localizes at the nuclear envelope independently of H3K9 methylation and nuclear lamin. CEC-4 is necessary for endogenous heterochromatin anchoring, but not for transcriptional repression, in contrast to other known H3K9 methyl-binders in worms, which mediate gene repression but not perinuclear anchoring. When we ectopically induce a muscle differentiation program in embryos, cec-4 mutants fail to commit fully to muscle cell fate. This suggests that perinuclear sequestration of chromatin during development helps restrict cell differentiation programs by stabilizing commitment to a specific cell fate. PAPERCLIP.

INO80-C and SWR-C: guardians of the genome.

The double membrane of the eukaryotic nucleus surrounds the genome, constraining it to a nuclear sphere. Proteins, RNA protein particles and artificial chromosome rings diffuse rapidly and freely throughout the nucleoplasm, while chromosomal loci show subdiffusive movement with varying degrees of constraint. In situ biochemical approaches and live imaging studies have revealed the existence of nuclear subcompartments that are enriched for specific chromatin states and/or enzymatic activities. This sequestration is thought to enhance the formation of heterochromatin, particularly when factors of limited abundance are involved. Implicit in the concept of compartmentation is the idea that chromatin is able to move from one compartment to another. Indeed, in budding yeast, gene activation, repression and the presence of persistent DNA double-strand breaks each has been shown to provoke subnuclear relocalization of chromatin. In some cases, movement has been linked to the action of ATP-dependent chromatin remodeling complexes, more specifically to the Snf2-related ATPase-containing complexes, SWR-C and INO80-C. Here we examine how these multi-subunit remodelers contribute to chromatin-based processes linked to the DNA damage response. We review recent evidence that supports a role for yeast SWR-C and INO80-C in determining the subnuclear position of damaged domains and finally, we recap the multiple ways in which these remodelers contribute to genomic integrity.

SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice.

Persistent DNA double-strand breaks (DSBs) are recruited to the nuclear periphery in budding yeast. Both the Nup84 pore subcomplex and Mps3, an inner nuclear membrane (INM) SUN domain protein, have been implicated in DSB binding. It was unclear what, if anything, distinguishes the two potential sites of repair. Here, we characterize and distinguish the two binding sites. First, DSB-pore interaction occurs independently of cell-cycle phase and requires neither the chromatin remodeler INO80 nor recombinase Rad51 activity. In contrast, Mps3 binding is S and G2 phase specific and requires both factors. SWR1-dependent incorporation of Htz1 (H2A.Z) is necessary for break relocation to either site in both G1- and S-phase cells. Importantly, functional assays indicate that mutations in the two sites have additive repair defects, arguing that the two perinuclear anchorage sites define distinct survival pathways.

Effective dose to patient measurements in flat-detector and multislice computed tomography: a comparison of applications in neuroradiology.

PURPOSE: Flat-detector CT (FD-CT) is used for a variety of applications. Additionally, 3D rotational angiography (3D DSA) is used to supplement digital subtraction angiography (DSA) studies. The aim was to measure and compare the dose of (1) standard DSA and 3D DSA and (2) analogous FD-CT and multislice CT (MSCT) protocols. METHODS: Using an anthropomorphic phantom, the effective dose to patients (according to ICRP 103) was measured on an MSCT and a flat-detector angiographic system using standard protocols as recommended by the manufacturer. RESULTS: (1) Evaluation of DSA and 3D DSA angiography protocols: ap.-lat. Standard/low-dose series 1/0.8 mSv, enlarged oblique projection 0.3 mSv, 3D DSA 0.9 mSv (limited coverage length 0.3 mSv). (2) Comparison of FD-CT and MSCT: brain parenchyma imaging 2.9 /1.4 mSv, perfusion imaging 2.3/4.2 mSv, temporal bone 0.2 /0.2 mSv, angiography 2.9/3.3 mSv, limited to the head using collimation 0.5/0.5 mSv. CONCLUSION: The effective dose for an FD-CT application depends on the application used. Using collimation for FD-CT applications, the dose may be reduced considerably. Due to the low dose of 3D DSA, we recommend using this technique to reduce the number of DSA series needed to identify working projections. KEY POINTS: Effective dose of FD-CT in comparison to MSCT is in comparable range. Collimation decreases the dose of FD-CT effectively. Effective dose of 3-D angiography is identical to 2-D DSA. Different FD-CT programs have different dose.

Structures of Cas9 endonucleases reveal RNA-mediated conformational activation.

Type II CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems use an RNA-guided DNA endonuclease, Cas9, to generate double-strand breaks in invasive DNA during an adaptive bacterial immune response. Cas9 has been harnessed as a powerful tool for genome editing and gene regulation in many eukaryotic organisms. We report 2.6 and 2.2 angstrom resolution crystal structures of two major Cas9 enzyme subtypes, revealing the structural core shared by all Cas9 family members. The architectures of Cas9 enzymes define nucleic acid binding clefts, and single-particle electron microscopy reconstructions show that the two structural lobes harboring these clefts undergo guide RNA-induced reorientation to form a central channel where DNA substrates are bound. The observation that extensive structural rearrangements occur before target DNA duplex binding implicates guide RNA loading as a key step in Cas9 activation.

Nucleosome remodelers in double-strand break repair.

ATP-dependent nucleosome remodelers use ATP hydrolysis to shift, evict and exchange histone dimers or octamers and have well-established roles in transcription. Earlier work has suggested a role for nucleosome remodelers such as INO80 in double-strand break (DSB) repair. This review will begin with an update on recent studies that explore how remodelers are recruited to DSBs. We then examine their impact on various steps of repair, focusing on resection and the formation of the Rad51-ssDNA nucleofilament. Finally, we will explore new studies that implicate remodelers in the physical movement of chromatin in response to damage.

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.