Community health worker perspectives on advocacy: design-based research to develop a digital advocacy training course.

Introduction: While community health workers (CHWs) are well-positioned as health advocates, they frequently lack support and feel undervalued. Advocacy training may prepare CHWs to support communities better. Methods: This study uses a design-based research approach to (1) explore how participation in curriculum-development workshops for a digital advocacy course influenced CHWs' (n = 25) perceptions of advocacy and (2) describe how CHW involvement shaped course development. Data were collected via five discussion groups and seven surveys over six months. Results: Initially, the CHWs perceived themselves as community-advocates but not as self-advocates. They increasingly reflected on the merits of advocating for better working conditions and aspired to greater involvement in decision-making. CHWs reflected positively on their advisory role in shaping the course to improve content acceptability and validity. Discussion: Training efforts to engage CHWs in advocacy must overcome systemic barriers and norms internalized by CHWs that deter them from reaching their full potential as advocates.

Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.

Meta-analysis of genome-wide association study data has implicated PDE4B in the pathogenesis of Alzheimer's disease (AD), the leading cause of senile dementia. PDE4B encodes one of four subtypes of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase-4 (PDE4A-D). To interrogate the involvement of PDE4B in the manifestation of AD-related phenotypes, the effects of a hypomorphic mutation (Pde4bY358C) that decreases PDE4B's cAMP hydrolytic activity were evaluated in the AppNL-G-F knock-in mouse model of AD using the Barnes maze test of spatial memory, 14C-2-deoxyglucose autoradiography, thioflavin-S staining of ß-amyloid (Aß) plaques, and inflammatory marker assay and transcriptomic analysis (RNA sequencing) of cerebral cortical tissue. At 12 months of age, AppNL-G-F mice exhibited spatial memory and brain metabolism deficits, which were prevented by the hypomorphic PDE4B in AppNL-G-F/Pde4bY358C mice, without a decrease in Aß plaque burden. RNA sequencing revealed that, among the 531 transcripts differentially expressed in AppNL-G-F versus wild-type mice, only 13 transcripts from four genes - Ide, Btaf1, Padi2, and C1qb - were differentially expressed in AppNL-G-F/Pde4bY358C versus AppNL-G-F mice, identifying their potential involvement in the protective effect of hypomorphic PDE4B. Our data demonstrate that spatial memory and cerebral glucose metabolism deficits exhibited by 12-month-old AppNL-G-F mice are prevented by targeted inhibition of PDE4B. To our knowledge, this is the first demonstration of a protective effect of PDE4B subtype-specific inhibition in a preclinical model of AD. It thus identifies PDE4B as a key regulator of disease manifestation in the AppNL-G-F model and a promising therapeutic target for AD.

Exploring the role of community health organizations in promoting public health during a health crisis: a qualitative study of COVID-19 responses in South Africa and Zambia.

While the COVID-19 pandemic amplified the need for accurate and actionable health information, uncertainty and the proliferation of misinformation have contributed to significant mistrust in public health messages, especially among marginalized communities. Community health organizations can play an important role in creating trust and providing targeted health information to vulnerable groups. This qualitative study, which is focused on community health organizations supporting vulnerable populations in South Africa and Zambia, finds that during the pandemic, community health organizations expanded their roles and leveraged their established access and trust to support the communities they serve with health education and services. However, the reliance on external support limits the organizations' ability to respond in an effective and efficient manner during health crises.

The Use of Open-Source Online Course Content for Training in Public Health Emergencies: Mixed Methods Case Study of a COVID-19 Course Series for Health Professionals.

BACKGROUND: The onset of the COVID-19 pandemic generated an urgent need for credible and actionable information to guide public health responses. The massive open-source online course (MOOC) format may be a valuable path for disseminating timely and widely accessible training for health professionals during public health crises; however, the reach and effectiveness of health worker-directed online courses during the pandemic remain largely unexplored. OBJECTIVE: This study investigated the use of an open-source online course series designed to provide critical COVID-19 knowledge to frontline health workers and public health professionals globally. The study investigated how open-source online educational content can be optimized to support knowledge sharing among health professionals in public health emergencies, particularly in resource-limited contexts. METHODS: The study examined global course enrollment patterns (N=2185) and performed in-depth interviews with a purposive subsample of health professionals enrolled in the course series (N=12) to investigate the sharing of online content in pandemic responses. Interviewed learners were from Ethiopia, India, Kenya, Liberia, Malawi, Rwanda, Thailand, Uganda, the United Arab Emirates, and the United States. Inductive analysis and constant comparative methods were used to systematically code data and identify key themes emerging from interview data. RESULTS: The analysis revealed that the online course content helped fill a critical gap in trustworthy COVID-19 information for pandemic responses and was shared through health worker professional and personal networks. Enrollment patterns and qualitative data illustrate how health professionals shared information within their professional networks. While learners shared the knowledge they gained from the course, they expressed a need for contextualized information to more effectively educate others in their networks and in their communities. Due to technological and logistical barriers, participants did not attempt to adapt the content to share with others. CONCLUSIONS: This study illustrates that health professional networks can facilitate the sharing of online open-source health education content; however, to fully leverage potential benefits, additional support is required to facilitate the adaptation of course content to more effectively reach communities globally.

Barriers to COVID-19 vaccine acceptance to improve messages for vaccine uptake in indigenous populations in the central highlands of Guatemala: a participatory qualitative study.

INTRODUCTION: As of July 2022, a little over one-third of Guatemalans were fully vaccinated. While COVID-19 vaccination rates are not officially reported nationally by racial/ethnic groups, non-governmental organisations and reporters have observed that COVID-19 vaccination rates are especially low among high-risk Indigenous populations. We conducted one of the first studies on COVID-19 vaccine acceptance in Indigenous populations in the Central Highlands of Guatemala, which aimed to better understand the barriers to COVID-19 vaccine uptake and how to improve vaccine promotional campaigns. METHODS: In November 2021, we conducted eight focus group discussions (FGDs) with 42 Indigenous men and women and 16 in-depth interviews (IDIs) with community health workers, nurses and physicians in Chimaltenango and Sololá. Using a participatory design approach, our qualitative analysis used constant comparative methods to understand the inductive and deductive themes from the FGD and IDI transcripts. RESULTS: We found three major overarching barriers to vaccination within the sampled population: (1) a lack of available easily understandable, linguistically appropriate and culturally sensitive COVID-19 vaccine information; (2) vaccine access and supply issues that prevented people from being vaccinated efficiently and quickly; and (3) widespread misinformation and disinformation that prey on people's fears of the unknown and mistrust of the medical establishment and government. CONCLUSION: When developing COVID-19 vaccine messages, content should be culturally relevant, appropriate for low-literacy populations and in the languages that people prefer to speak. Promotional materials should be in multiple modalities (print, radio and social media) and also have specific Maya cultural references (dress, food and concepts of disease) to ensure messaging connects with intended targets. This study supports the need for more robust research into best practices for communicating about COVID-19 vaccines to marginalised communities globally and suggests that policy makers should invest in targeted local solutions to increase vaccine uptake.

Graded spikes differentially signal neurotransmitter input in cerebrospinal fluid contacting neurons of the mouse spinal cord.

The action potential and its all-or-none nature is fundamental to neural communication. Canonically, the action potential is initiated once voltage-activated Na+ channels are activated, and their rapid kinetics of activation and inactivation give rise to the action potential's all-or-none nature. Here we demonstrate that cerebrospinal fluid contacting neurons (CSFcNs) surrounding the central canal of the mouse spinal cord employ a different strategy. Rather than using voltage-activated Na+ channels to generate binary spikes, CSFcNs use two different types of voltage-activated Ca2+ channel, enabling spikes of different amplitude. T-type Ca2+ channels generate small amplitude spikes, whereas larger amplitude spikes require high voltage-activated Cd2+-sensitive Ca2+ channels. We demonstrate that these different amplitude spikes can signal input from different transmitter systems; purinergic inputs evoke smaller T-type dependent spikes whereas cholinergic inputs evoke larger spikes that do not rely on T-type channels. Different synaptic inputs to CSFcNs can therefore be signaled by the spike amplitude.

Evaluating the impact of a linguistically and culturally tailored social media ad campaign on COVID-19 vaccine uptake among indigenous populations in Guatemala: a pre/post design intervention study.

OBJECTIVES: To evaluate the impact of culturally and linguistically tailored informational videos delivered via social media campaigns on COVID-19 vaccine uptake in Indigenous Maya communities in Guatemala. METHODS: Our team designed a series of videos utilising community input and evaluated the impact using a pre-post intervention design. In-person preintervention surveys were collected from a sample of respondents in four rural municipalities in Guatemala in March 2022. Facebook, Instagram and browser ads were flooded with COVID-19 vaccine informational videos in Spanish, Kaqchikel and Kiche for 3 weeks. Postintervention surveys were conducted by telephone among the same participants in April 2022. Logistic regression models were used to estimate the OR of COVID-19 vaccine uptake following exposure to the intervention videos. RESULTS: Preintervention and postintervention surveys were collected from 1572 participants. The median age was 28 years; 63% (N=998) identified as women, and 36% spoke an Indigenous Mayan language. Twenty-one per cent of participants (N=327) reported watching the intervention content on social media. At baseline, 89% (N=1402) of participants reported having at least one COVID-19 vaccine, compared with 97% (N=1507) in the follow-up. Those who reported watching the videos had 1.78 times the odds (95% CI 1.14 to 2.77) of getting vaccinated after watching the videos compared with those who did not see the videos when adjusted by age, community, sex and language. CONCLUSION: Our findings suggest that culturally and linguistically tailored videos addressing COVID-19 vaccine misinformation deployed over social media can increase vaccinations in a rural, indigenous population in Guatemala, implying that social media content can influence vaccination uptake. Providing accurate, culturally sensitive information in local languages from trusted sources may help increase vaccine uptake in historically marginalised populations.

Correction: Teaching From Afar: Development of a Telemedicine Curriculum for Healthcare Workers in Global Settings.

[This corrects the article DOI: 10.7759/cureus.20123.].

"The Videos Gave Weight to Our Work": Animated mHealth Videos and Tablet Technology Boost Community Health Workers' Perceived Credibility in Khayelitsha, South Africa.

Mobile health (mHealth) interventions are increasingly used to support community health workers (CHWs) in low-and middle-income countries. As near-peers within their communities, the credibility of CHWs is sometimes questioned-a recognized barrier to their efficacy. Nested within a large, randomized-controlled trial, this qualitative study captured the experiences of South African CHWs, called "Mentor-Mothers," using tablets and animated videos to promote exclusive breastfeeding. We conducted in-depth telephone interviews with 26 tablet-carrying Mentor-Mothers. We analyzed interview transcripts using a Grounded Theory approach, then developed a theoretical framework, based on an emerging theme, for understanding how tablet technology boosts the perceived credibility of CHWs. Tablet-carrying Mentor-Mothers described an increase in their perceived credibility, which they attributed to overt and signaling effects related to enhanced credibility of (1) their messages, (2) themselves as messengers, and (3) the program employing them. Mobile technology investments in CHWs could enhance their credibility, translating into meaningful investments in the health of under-served communities.

Post-translational modification patterns on ß-myosin heavy chain are altered in ischemic and nonischemic human hearts.

Phosphorylation and acetylation of sarcomeric proteins are important for fine-tuning myocardial contractility. Here, we used bottom-up proteomics and label-free quantification to identify novel post-translational modifications (PTMs) on ß-myosin heavy chain (ß-MHC) in normal and failing human heart tissues. We report six acetylated lysines and two phosphorylated residues: K34-Ac, K58-Ac, S210-P, K213-Ac, T215-P, K429-Ac, K951-Ac, and K1195-Ac. K951-Ac was significantly reduced in both ischemic and nonischemic failing hearts compared to nondiseased hearts. Molecular dynamics (MD) simulations show that K951-Ac may impact stability of thick filament tail interactions and ultimately myosin head positioning. K58-Ac altered the solvent-exposed SH3 domain surface - known for protein-protein interactions - but did not appreciably change motor domain conformation or dynamics under conditions studied. Together, K213-Ac/T215-P altered loop 1's structure and dynamics - known to regulate ADP-release, ATPase activity, and sliding velocity. Our study suggests that ß-MHC acetylation levels may be influenced more by the PTM location than the type of heart disease since less protected acetylation sites are reduced in both heart failure groups. Additionally, these PTMs have potential to modulate interactions between ß-MHC and other regulatory sarcomeric proteins, ADP-release rate of myosin, flexibility of the S2 region, and cardiac myofilament contractility in normal and failing hearts.

Diurnal changes in the efficiency of information transmission at a sensory synapse.

Neuromodulators adapt sensory circuits to changes in the external world or the animal's internal state and synapses are key control sites for such plasticity. Less clear is how neuromodulation alters the amount of information transmitted through the circuit. We investigated this question in the context of the diurnal regulation of visual processing in the retina of zebrafish, focusing on ribbon synapses of bipolar cells. We demonstrate that contrast-sensitivity peaks in the afternoon accompanied by a four-fold increase in the average Shannon information transmitted from an active zone. This increase reflects higher synaptic gain, lower spontaneous "noise" and reduced variability of evoked responses. Simultaneously, an increase in the probability of multivesicular events with larger information content increases the efficiency of transmission (bits per vesicle) by factors of 1.5-2.7. This study demonstrates the multiplicity of mechanisms by which a neuromodulator can adjust the synaptic transfer of sensory information.

Digital Education for Health Professionals: An Evidence Map, Conceptual Framework, and Research Agenda.

BACKGROUND: Health professions education has undergone major changes with the advent and adoption of digital technologies worldwide. OBJECTIVE: This study aims to map the existing evidence and identify gaps and research priorities to enable robust and relevant research in digital health professions education. METHODS: We searched for systematic reviews on the digital education of practicing and student health care professionals. We searched MEDLINE, Embase, Cochrane Library, Educational Research Information Center, CINAHL, and gray literature sources from January 2014 to July 2020. A total of 2 authors independently screened the studies, extracted the data, and synthesized the findings. We outlined the key characteristics of the included reviews, the quality of the evidence they synthesized, and recommendations for future research. We mapped the empirical findings and research recommendations against the newly developed conceptual framework. RESULTS: We identified 77 eligible systematic reviews. All of them included experimental studies and evaluated the effectiveness of digital education interventions in different health care disciplines or different digital education modalities. Most reviews included studies on various digital education modalities (22/77, 29%), virtual reality (19/77, 25%), and online education (10/77, 13%). Most reviews focused on health professions education in general (36/77, 47%), surgery (13/77, 17%), and nursing (11/77, 14%). The reviews mainly assessed participants' skills (51/77, 66%) and knowledge (49/77, 64%) and included data from high-income countries (53/77, 69%). Our novel conceptual framework of digital health professions education comprises 6 key domains (context, infrastructure, education, learners, research, and quality improvement) and 16 subdomains. Finally, we identified 61 unique questions for future research in these reviews; these mapped to framework domains of education (29/61, 47% recommendations), context (17/61, 28% recommendations), infrastructure (9/61, 15% recommendations), learners (3/61, 5% recommendations), and research (3/61, 5% recommendations). CONCLUSIONS: We identified a large number of research questions regarding digital education, which collectively reflect a diverse and comprehensive research agenda. Our conceptual framework will help educators and researchers plan, develop, and study digital education. More evidence from low- and middle-income countries is needed.

Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy.

Background Pediatric dilated cardiomyopathy (DCM) is a well-known clinical entity; however, phenotype-genotype correlations are inadequately described. Our objective was to provide genotype associations with life-threatening cardiac outcomes in pediatric DCM probands. Methods and Results We performed a retrospective review of children with DCM at a large pediatric referral center (2007-2016), excluding syndromic, chemotherapy-induced, and congenital heart disease causes. Genetic variants were adjudicated by an expert panel and an independent clinical laboratory. In a cohort of 109 pediatric DCM cases with a mean age at diagnosis of 4.2 years (SD 5.9), life-threatening cardiac outcomes occurred in 47% (42% heart transplant, 5% death). One or more pathogenic/likely pathogenic variants were present in 40/109 (37%), and 36/44 (82%) of pathogenic/likely pathogenic variants occurred in sarcomeric genes. The frequency of pathogenic/likely pathogenic variants was not different in patients with familial cardiomyopathy (15/33 with family history versus 25/76 with no family history, P=0.21). TTN truncating variants occurred in a higher percentage of children diagnosed as teenagers (26% teenagers versus 6% younger children, P=0.01), but life-threatening cardiac outcomes occurred in both infants and teenagers with these TTN variants. DCM with left ventricular noncompaction features occurred in 6/6 patients with MYH7 variants between amino acids 1 and 600. Conclusions Sarcomeric variants were common in pediatric DCM. We demonstrated genotype-specific associations with age of diagnosis and cardiac outcomes. In particular, MYH7 had domain-specific association with DCM with left ventricular noncompaction features. Family history did not predict pathogenic/likely pathogenic variants, reinforcing that genetic testing should be considered in all children with idiopathic DCM.

Genetic correction strategies for Duchenne Muscular Dystrophy and their impact on the heart.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with early childhood onset characterized by profound loss of muscle strength and associated cardiomyopathy. DMD affects is most often caused by deletions involving single or multiple exons that disrupt the open reading frame of the DMD gene. Mutations causing loss or premature truncation of dystrophin result in dystrophin protein deficiency, which renders the plasma membrane of skeletal myofibers and cardiomyocytes weakened. AIM OF REVIEW: Genetic correction is in use to treat DMD, since several drugs have been already approved which partially restore dystrophin production through the use of antisense oligonucleotides. There are multiple ongoing clinical trials to evaluate the efficacy of treating DMD with micro-dystrophins delivered by adeno-associated viruses. Future approaches entail gene editing to target the single copy of the DMD gene on the X-chromosome. The primary, near-term goal is restoration of skeletal muscle dystrophin, and for some of these treatments, the efficacy in the heart is not fully known. Here, we discuss the anticipated cardiac outcomes of dystrophin-targeted therapies, and how this information informs genomic medicine for cardiomyopathies, especially in childhood. KEY SCIENTIFIC CONCEPTS OF REVIEW: Many genetic treatment strategies are being implemented to treat DMD. Since most preclinical testing has focused on skeletal muscle, there is a gap in knowledge about the expected effects of these approaches on cardiac genetic correction and cardiomyopathy progression in DMD. Additional study is needed.

Evaluation of a community-based mobile video breastfeeding intervention in Khayelitsha, South Africa: The Philani MOVIE cluster-randomized controlled trial.

BACKGROUND: In South Africa, breastfeeding promotion is a national health priority. Regular perinatal home visits by community health workers (CHWs) have helped promote exclusive breastfeeding (EBF) in underresourced settings. Innovative, digital approaches including mobile video content have also shown promise, especially as access to mobile technology increases among CHWs. We measured the effects of an animated, mobile video series, the Philani MObile Video Intervention for Exclusive breastfeeding (MOVIE), delivered by a cadre of CHWs ("mentor mothers"). METHODS AND FINDINGS: We conducted a stratified, cluster-randomized controlled trial from November 2018 to March 2020 in Khayelitsha, South Africa. The trial was conducted in collaboration with the Philani Maternal Child Health and Nutrition Trust, a nongovernmental community health organization. We quantified the effect of the MOVIE intervention on EBF at 1 and 5 months (primary outcomes), and on other infant feeding practices and maternal knowledge (secondary outcomes). We randomized 1,502 pregnant women in 84 clusters 1:1 to 2 study arms. Participants' median age was 26 years, 36.9% had completed secondary school, and 18.3% were employed. Mentor mothers in the video intervention arm provided standard-of-care counseling plus the MOVIE intervention; mentor mothers in the control arm provided standard of care only. Within the causal impact evaluation, we nested a mixed-methods performance evaluation measuring mentor mothers' time use and eliciting their subjective experiences through in-depth interviews. At both points of follow-up, we observed no statistically significant differences between the video intervention and the control arm with regard to EBF rates and other infant feeding practices [EBF in the last 24 hours at 1 month: RR 0.93 (95% CI 0.86 to 1.01, P = 0.091); EBF in the last 24 hours at 5 months: RR 0.90 (95% CI 0.77 to 1.04, P = 0.152)]. We observed a small, but significant improvement in maternal knowledge at the 1-month follow-up, but not at the 5-month follow-up. The interpretation of the results from this causal impact evaluation changes when we consider the results of the nested mixed-methods performance evaluation. The mean time spent per home visit was similar across study arms, but the intervention group spent approximately 40% of their visit time viewing videos. The absence of difference in effects on primary and secondary endpoints implies that, for the same time investment, the video intervention was as effective as face-to-face counseling with a mentor mother. The videos were also highly valued by mentor mothers and participants. Study limitations include a high loss to follow-up at 5 months after premature termination of the trial due to the COVID-19 pandemic and changes in mentor mother service demarcations. CONCLUSIONS: This trial measured the effect of a video-based, mobile health (mHealth) intervention, delivered by CHWs during home visits in an underresourced setting. The videos replaced about two-fifths of CHWs' direct engagement time with participants in the intervention arm. The similar outcomes in the 2 study arms thus suggest that the videos were as effective as face-to-face counselling, when CHWs used them to replace a portion of that counselling. Where CHWs are scarce, mHealth video interventions could be a feasible and practical solution, supporting the delivery and scaling of community health promotion services. TRIAL REGISTRATION: The study and its outcomes were registered at clinicaltrials.gov (#NCT03688217) on September 27, 2018.

Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy.

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca2+-regulation of myocardial contraction. Here, we report the molecular basis of a human mutation in cTnC's αD-helix (TNNC1-p.C84Y) that impacts conformational dynamics of the D/E central-linker and sampling of discrete states in the N-domain, favoring the "primed" state associated with Ca2+ binding. We demonstrate cTnC's αD-helix normally functions as a central hub that controls minimally frustrated interactions, maintaining evolutionarily conserved rigidity of the N-domain. αD-helix perturbation remotely alters conformational dynamics of the N-domain, compromising its structural rigidity. Transgenic mice carrying this cTnC mutation exhibit altered dynamics of sarcomere function and hypertrophic cardiomyopathy. Together, our data suggest that disruption of evolutionary conserved molecular frustration networks by a myofilament protein mutation may ultimately compromise contractile performance and trigger hypertrophic cardiomyopathy.

Design preferences for global scale: a mixed-methods study of "glocalization" of an animated, video-based health communication intervention.

BACKGROUND: Designing health communication interventions for global scaling promotes health literacy and facilitates rapid global health messaging. Limited literature explores preferences for animation prototypes and other content characteristics across participants in different global regions. Prior research underscores an urgent need for health communication interventions that are compelling and accessible across culturally and geographically diverse audiences. This study presents feedback from global learners on animation design preferences and other key considerations for the development of educational video content intended for global adaptation and scaling. METHODS: We used a mixed-methods, sequential explanatory design, with a qualitative descriptive approach to the analysis of the qualitative data. We recruited participants from an international group of learners enrolled in a massive open online course. Through an online quantitative survey (n = 330), we sought preferences from participants in 73 countries for animation design prototypes to be used in video-based health communication interventions. To learn more about these preferences, we conducted in-depth interviews (n = 20) with participants selected using maximum variation purposive sampling. RESULTS: Generally, respondents were willing to accept animation prototypes that were free of cultural and ethnic identifiers and believed these to be preferable for globally scalable health communication videos. Diverse representations of age, gender roles, and family structure were also preferred and felt to support inclusive messaging across cultures and global regions. Familiar-sounding voiceovers using local languages, dialects, and accents were preferred for enhancing local resonance. Across global regions, narratives were highlighted as a compelling approach to facilitating engagement and participants preferred short videos with no more than two or three health messages. CONCLUSIONS: Our findings suggest that global learners may be willing to accept simplified visuals, designed for broad cross-cultural acceptability, especially if the content is localized in other ways, such as through the use of locally resonating narratives and voiceovers. Diverse, inclusive portrayals of age, gender roles and family structure were preferred.

Pharmacology of A-Type K+ Channels.

Transient outward potassium currents were first described nearly 60 years ago, since then major strides have been made in understanding their molecular basis and physiological roles. From the large family of voltage-gated potassium channels members of 3 subfamilies can produce such fast-inactivating A-type potassium currents. Each subfamily gives rise to currents with distinct biophysical properties and pharmacological profiles and a simple workflow is provided to aid the identification of channels mediating A-type currents in native cells. Their unique properties and regulation enable A-type K+ channels to perform varied roles in excitable cells including repolarisation of the cardiac action potential, controlling spike and synaptic timing, regulating dendritic integration and long-term potentiation as well as being a locus of neural plasticity.

Epigenetic reprogramming to prevent genetic cardiomyopathy.

Mutations in the gene that codes for lamin A/C (LMNA) are a common cause of adult-onset cardiomyopathy and heart failure. In this issue of the JCI, Guénantin and Jebeniani et al. identify impaired cardiomyocyte development and maturation as a prenatal feature in a model of laminopathy. Cardiomyocytes carrying the Lmna point mutation H222P misexpressed genes involved in the epithelial-mesenchymal transition and showed decreased methylation at the fourth lysine of histone H3 (H3K4). Notably, inhibiting lysine-specific demethylase 1 in the LMNA H222P mouse model treated this congenital form of cardiomyopathy and improved survival in utero. These data highlight early epigenomic modifications in lamin A/C-mediated pathology and indicate a unique therapeutic strategy for cardiomyopathy.