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.

"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.

Mutation location of HCM-causing troponin T mutations defines the degree of myofilament dysfunction in human cardiomyocytes.

BACKGROUND: The clinical outcome of hypertrophic cardiomyopathy patients is not only determined by the disease-causing mutation but influenced by a variety of disease modifiers. Here, we defined the role of the mutation location and the mutant protein dose of the troponin T mutations I79N, R94C and R278C. METHODS AND RESULTS: We determined myofilament function after troponin exchange in permeabilized single human cardiomyocytes as well as in cardiac patient samples harboring the R278C mutation. Notably, we found that a small dose of mutant protein is sufficient for the maximal effect on myofilament Ca2+-sensitivity for the I79N and R94C mutation while the mutation location determines the magnitude of this effect. While incorporation of I79N and R94C increased myofilament Ca2+-sensitivity, incorporation of R278C increased Ca2+-sensitivity at low and intermediate dose, while it decreased Ca2+-sensitivity at high dose. All three cTnT mutants showed reduced thin filament binding affinity, which coincided with a relatively low maximal exchange (50.5 ± 5.2%) of mutant troponin complex in cardiomyocytes. In accordance, 32.2 ± 4.0% mutant R278C was found in two patient samples which showed 50.0 ± 3.7% mutant mRNA. In accordance with studies that showed clinical variability in patients with the exact same mutation, we observed variability on the functional single cell level in patients with the R278C mutation. These differences in myofilament properties could not be explained by differences in the amount of mutant protein. CONCLUSIONS: Using troponin exchange in single human cardiomyocytes, we show that TNNT2 mutation-induced changes in myofilament Ca2+-sensitivity depend on mutation location, while all mutants show reduced thin filament binding affinity. The specific mutation-effect observed for R278C could not be translated to myofilament function of cardiomyocytes from patients, and is most likely explained by other (post)-translational troponin modifications. Overall, our studies illustrate that mutation location underlies variability in myofilament Ca2+-sensitivity, while only the R278C mutation shows a highly dose-dependent effect on myofilament function.

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.

A comprehensive guide to genetic variants and post-translational modifications of cardiac troponin C.

Familial cardiomyopathy is an inherited disease that affects the structure and function of heart muscle and has an extreme range of phenotypes. Among the millions of affected individuals, patients with hypertrophic (HCM), dilated (DCM), or left ventricular non-compaction (LVNC) cardiomyopathy can experience morphologic changes of the heart which lead to sudden death in the most detrimental cases. TNNC1, the gene that codes for cardiac troponin C (cTnC), is a sarcomere gene associated with cardiomyopathies in which probands exhibit young age of presentation and high death, transplant or ventricular fibrillation events relative to TNNT2 and TNNI3 probands. Using GnomAD, ClinVar, UniProt and PhosphoSitePlus databases and published literature, an extensive list to date of identified genetic variants in TNNC1 and post-translational modifications (PTMs) in cTnC was compiled. Additionally, a recent cryo-EM structure of the cardiac thin filament regulatory unit was used to localize each functionally studied amino acid variant and each PTM (acetylation, glycation, s-nitrosylation, phosphorylation) in the structure of cTnC. TNNC1 has a large number of variants (> 100) relative to other genes of the same transcript size. Surprisingly, the mapped variant amino acids and PTMs are distributed throughout the cTnC structure. While many cardiomyopathy-associated variants are localized in α-helical regions of cTnC, this was not statistically significant χ2 (p = 0.72). Exploring the variants in TNNC1 and PTMs of cTnC in the contexts of cardiomyopathy association, physiological modulation and potential non-canonical roles provides insights into the normal function of cTnC along with the many facets of TNNC1 as a cardiomyopathic gene.

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.

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.

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.

The intrinsically disordered C terminus of troponin T binds to troponin C to modulate myocardial force generation.

Aberrant regulation of myocardial force production represents an early biomechanical defect associated with sarcomeric cardiomyopathies, but the molecular mechanisms remain poorly defined. Here, we evaluated the pathogenicity of a previously unreported sarcomeric gene variant identified in a pediatric patient with sporadic dilated cardiomyopathy, and we determined a molecular mechanism. Trio whole-exome sequencing revealed a de novo missense variant in TNNC1 that encodes a p.I4M substitution in the N-terminal helix of cardiac troponin C (cTnC). Reconstitution of this human cTnC variant into permeabilized porcine cardiac muscle preparations significantly decreases the magnitude and rate of isometric force generation at physiological Ca2+-activation levels. Computational modeling suggests that this inhibitory effect can be explained by a decrease in the rates of cross-bridge attachment and detachment. For the first time, we show that cardiac troponin T (cTnT), in part through its intrinsically disordered C terminus, directly binds to WT cTnC, and we find that this cardiomyopathic variant displays tighter binding to cTnT. Steady-state fluorescence and NMR spectroscopy studies suggest that this variant propagates perturbations in cTnC structural dynamics to distal regions of the molecule. We propose that the intrinsically disordered C terminus of cTnT directly interacts with the regulatory N-domain of cTnC to allosterically modulate Ca2+ activation of force, perhaps by controlling the troponin I switching mechanism of striated muscle contraction. Alterations in cTnC-cTnT binding may compromise contractile performance and trigger pathological remodeling of the myocardium.

The Philani MOVIE study: a cluster-randomized controlled trial of a mobile video entertainment-education intervention to promote exclusive breastfeeding in South Africa.

BACKGROUND: In South Africa, rates of exclusive breastfeeding remain low and breastfeeding promotion is a national health priority. Mobile health and narrative entertainment-education are recognized strategies for health promotion. In-home counseling by community health workers (CHWs) is a proven breastfeeding promotion strategy. This protocol outlines a cluster-randomized controlled trial with a nested mixed-methods evaluation of the MObile Video Intervention for Exclusive breastfeeding (MOVIE) program. The evaluation will quantify the causal effect of the MOVIE program and generate a detailed understanding of the context in which the intervention took place and the mechanisms through which it enacted change. Findings from the study will inform the anticipated scale-up of mobile video health interventions in South Africa and the wider sub-Saharan region. METHODS: We will conduct a stratified cluster-randomized controlled trial in urban communities of the Western Cape, to measure the effect of the MOVIE intervention on exclusive breastfeeding and other infant feeding practices. Eighty-four mentor-mothers (CHWs employed by the Philani Maternal Child Health and Nutrition Trust) will be randomized 1:1 into intervention and control arms, stratified by neighborhood type. Mentor-mothers in the control arm will provide standard of care (SoC) perinatal in-home counseling. Mentor-mothers in the intervention arm will provide SoC plus the MOVIE intervention. At least 1008 pregnant participants will be enrolled in the study and mother-child pairs will be followed until 5 months post-delivery. The primary outcomes of the study are exclusive breastfeeding at 1 and 5 months of age. Secondary outcomes are other infant feeding practices and maternal knowledge. In order to capture human-centered underpinnings of the intervention, we will conduct interviews with stakeholders engaged in the intervention design. To contextualize quantitative findings and understand the mechanisms through which the intervention enacted change, end-line focus groups with mentor-mothers will be conducted. DISCUSSION: This trial will be among the first to explore a video-based, entertainment-education intervention delivered by CHWs and created using a community-based, human-centered design approach. As such, it could inform health policy, with regards to both the routine adoption of this intervention and, more broadly, the development of other entertainment-education interventions for health promotion in under-resourced settings. TRIAL REGISTRATION: The study and its outcomes were registered at clinicaltrials.gov ( #NCT03688217 ) on September 27th, 2018.

Structural and functional impact of troponin C-mediated Ca2+ sensitization on myofilament lattice spacing and cross-bridge mechanics in mouse cardiac muscle.

Acto-myosin cross-bridge kinetics are important for beat-to-beat regulation of cardiac contractility; however, physiological and pathophysiological mechanisms for regulation of contractile kinetics are incompletely understood. Here we explored whether thin filament-mediated Ca2+ sensitization influences cross-bridge kinetics in permeabilized, osmotically compressed cardiac muscle preparations. We used a murine model of hypertrophic cardiomyopathy (HCM) harboring a cardiac troponin C (cTnC) Ca2+-sensitizing mutation, Ala8Val in the regulatory N-domain. We also treated wild-type murine muscle with bepridil, a cTnC-targeting Ca2+ sensitizer. Our findings suggest that both methods of increasing myofilament Ca2+ sensitivity increase cross-bridge cycling rate measured by the rate of tension redevelopment (kTR); force per cross-bridge was also enhanced as measured by sinusoidal stiffness and I1,1/I1,0 ratio from X-ray diffraction. Computational modeling suggests that Ca2+ sensitization through this cTnC mutation or bepridil accelerates kTR primarily by promoting faster cross-bridge detachment. To elucidate if myofilament structural rearrangements are associated with changes in kTR, we used small angle X-ray diffraction to simultaneously measure myofilament lattice spacing and isometric force during steady-state Ca2+ activations. Within in vivo lattice dimensions, lattice spacing and steady-state isometric force increased significantly at submaximal activation. We conclude that the cTnC N-domain controls force by modulating both the number and rate of cycling cross-bridges, and that the both methods of Ca2+ sensitization may act through stabilization of cTnC's D-helix. Furthermore, we propose that the transient expansion of the myofilament lattice during Ca2+ activation may be an additional factor that could increase the rate of cross-bridge cycling in cardiac muscle. These findings may have implications for the pathophysiology of HCM.

Myosin Rod Hypophosphorylation and CB Kinetics in Papillary Muscles from a TnC-A8V KI Mouse Model.

The cardiac troponin C (TnC)-A8V mutation is associated with hypertrophic and restrictive cardiomyopathy (HCM and RCM) in human and mice. The residue affected lies in the N-helix, a region known to affect Ca2+-binding affinity to the N-terminal domain. Here we report on the functional effects of this mutation in skinned papillary muscle fibers from homozygous knock-in TnC-A8V mice. Muscle fibers from left ventricle were activated at 25°C under the ionic conditions of working cardiomyocytes. The pCa-tension relationship showed a 3× increase in Ca2+-sensitivity and a decrease (0.8×) in cooperativity (nH) in mutant fibers. The elementary steps of the cross-bridge (CB) cycle were investigated by sinusoidal analysis. The ATP study revealed that there is no significant change in the affinity of ATP (K1) for the myosin head. In TnC-A8V mutant fibers, the CB detachment rate (k2) and its equilibrium constant (K2) increased (1.5×). The phosphate study revealed that rate constant of the force-generation step (k4) decreased (0.5×), reversal step (k-4) increased (2×), and the phosphate-release step (1/K5) increased (2×). Pro-Q Diamond staining of the skinned fibers samples revealed no significant changes in total phosphorylation of multiple sarcomeric proteins. Further investigation using liquid chromatography-tandem mass spectrometry revealed hypophosphorylation of the rod domain of myosin heavy chain in TnC-A8V mutant fibers compared to wild-type. Immunoblotting confirmed the results observed in the mass spectrometry analysis. The results suggest perturbed CB kinetics-possibly caused by changes in the α-myosin heavy chain phosphorylation profile-as a novel mechanism, to our knowledge, by which a mutation in TnC can have rippling effects in the myofilament and contribute to the pathogenesis of HCM/RCM.

Presynaptic T-type Ca2+ channels modulate dendrodendritic mitral-mitral and mitral-periglomerular connections in mouse olfactory bulb.

Mitral cells express low-voltage activated Cav3.3 channels on their distal apical tuft dendrites (McKay et al., 2006; Johnston and Delaney, 2010). They also discharge Na(+)-dependent dendritic action potentials and release glutamate from these dendrites. Around resting membrane potentials, between -65 and -50 mV, Cav3.x channels are a primary determinant of cytoplasmic [Ca(2+)]. In this study using C57 mice, we present evidence that subthreshold Cav3.x-mediated Ca(2+) influx modulates action potential evoked transmitter release and directly drives asynchronous release from distal tuft dendrites. Presynaptic hyperpolarization and selective block of Cav3.x channels with Z941 (Tringham et al., 2012) reduce mitral-to-mitral EPSP amplitude, increase the coefficient of variation of EPSPs, and increase paired-pulse ratios, consistent with a reduced probability of transmitter release. Both hyperpolarization and Cav3.x channel blockade reduce steady-state cytoplasmic [Ca(2+)] in the tuft dendrite without reducing action potential evoked Ca(2+) influx, suggesting that background [Ca(2+)] modulates evoked release. We demonstrate that Cav3.x-mediated Ca(2+) influx from even one mitral cell at membrane potentials between -65 and -50 mV is sufficient to produce feedback inhibition from periglomerular neurons. Deinactivation of Cav3.x channels by hyperpolarization increases T-type Ca(2+) influx upon repolarization and increases feedback inhibition to produce subthreshold modulation of the mitral-periglomerular reciprocal circuit.

Rapid mapping of visual receptive fields by filtered back projection: application to multi-neuronal electrophysiology and imaging.

Neurons in the visual system vary widely in the spatiotemporal properties of their receptive fields (RFs), and understanding these variations is key to elucidating how visual information is processed. We present a new approach for mapping RFs based on the filtered back projection (FBP), an algorithm used for tomographic reconstructions. To estimate RFs, a series of bars were flashed across the retina at pseudo-random positions and at a minimum of five orientations. We apply this method to retinal neurons and show that it can accurately recover the spatial RF and impulse response of ganglion cells recorded on a multi-electrode array. We also demonstrate its utility for in vivo imaging by mapping the RFs of an array of bipolar cell synapses expressing a genetically encoded Ca(2+) indicator. We find that FBP offers several advantages over the commonly used spike-triggered average (STA): (i) ON and OFF components of a RF can be separated; (ii) the impulse response can be reconstructed at sample rates of 125 Hz, rather than the refresh rate of a monitor; (iii) FBP reveals the response properties of neurons that are not evident using STA, including those that display orientation selectivity, or fire at low mean spike rates; and (iv) the FBP method is fast, allowing the RFs of all the bipolar cell synaptic terminals in a field of view to be reconstructed in under 4 min. Use of the FBP will benefit investigations of the visual system that employ electrophysiology or optical reporters to measure activity across populations of neurons.

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.

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.

Health Care Workers' Motivations for Enrolling in Massive Open Online Courses During a Public Health Emergency: Descriptive Analysis.

Background: Massive open online courses (MOOCs) are increasingly used to educate health care workers during public health emergencies. In early 2020, the World Health Organization (WHO) developed a series of MOOCs for COVID-19, introducing the disease and strategies to control its outbreak, with 6 courses specifically targeting health care workers as learners. In 2020, Stanford University also launched a MOOC designed to deliver accurate and timely education on COVID-19, equipping health care workers across the globe to provide health care safely and effectively to patients with the novel infectious disease. Although the use of MOOCs for just-in-time training has expanded during the pandemic, evidence is limited regarding the factors motivating health care workers to enroll in and complete courses, particularly in low-income countries (LICs) and lower-middle-income countries (LMICs). Objective: This study seeks to gain insights on the characteristics and motivations of learners turning to MOOCs for just-in-time training, to provide evidence that can better inform MOOC design to meet the needs of health care workers. We examine data from learners in 1 Stanford University and 6 WHO COVID-19 courses to identify (1) the characteristics of health care workers completing the courses and (2) the factors motivating them to enroll. Methods: We analyze (1) course registration data of the 49,098 health care workers who completed the 7 focal courses and (2) survey responses from 6272 course completers. The survey asked respondents to rank their motivations for enrollment and share feedback about their learning experience. We use descriptive statistics to compare responses by health care profession and by World Bank country income classification. Results: Health care workers completed the focal courses from all regions of the world, with nearly one-third (14,159/49,098, 28.84%) practicing in LICs and LMICs. Survey data revealed a diverse range of professional roles among the learners, including physicians (2171/6272, 34.61%); nurses (1599/6272, 25.49%); and other health care professionals such as allied health professionals, community health workers, paramedics, and pharmacists (2502/6272, 39.89%). Across all health care professions, the primary motivation to enroll was for personal learning to improve clinical practice. Continuing education credit was also an important motivator, particularly for nonphysicians and learners in LICs and LMICs. Course cost (3423/6272, 54.58%) and certification (4238/6272, 67.57%) were also important to a majority of learners. Conclusions: Our results demonstrate that a diverse range of health care professionals accessed MOOCs for just-in-time training during a public health emergency. Although all health care workers were motivated to improve their clinical practice, different factors were influential across professions and locations. These factors should be considered in MOOC design to meet the needs of health care workers, particularly those in lower-resource settings where alternative avenues for training may be limited.

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.

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.

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.