On-demand mobile hypertension training for primary health care workers in Nigeria: a pilot study.

BACKGROUND: Only one out of every ten Nigerian adults with hypertension has their blood pressure controlled. Health worker training is essential to improve hypertension diagnosis and treatment. In-person training has limitations that mobile, on-demand training might address. This pilot study evaluated a self-paced, case-based, mobile-optimized online training to diagnose and manage hypertension for Nigerian health workers. METHODS: Twelve hypertension training modules were developed, based on World Health Organization and Nigerian guidelines. After review by local academic and government partners, the course was piloted by Nigerian health workers at government-owned primary health centers. Primary care physician, nurse, and community health worker participants completed the course on their own smartphones. Before and after the course, hypertension knowledge was evaluated with multiple-choice questions. Learners provided feedback by responding to questions on a Likert scale. RESULTS: Out of 748 users who sampled the course, 574 enrolled, of whom 431 (75%) completed the course. The average pre-test score of completers was 65.4%, which increased to 78.2% on the post-test (P < 0.001, paired t-test). Health workers who were not part of existing hypertension control programs had lower pre-test scores and larger score gains. Most participants (96.1%) agreed that the training was applicable to their work, and nearly all (99.8%) agreed that they enjoyed the training. CONCLUSIONS: An on-demand mobile digital hypertension training increases knowledge of hypertension management among Nigerian health workers. If offered at scale, such courses can be a tool to build health workforce capacity through initial and refresher training on current clinical guidelines in hypertension and other chronic diseases in Nigeria as well as other countries.

Coupling of saccade plans to endogenous attention during urgent choices.

The neural mechanisms that willfully direct attention to specific locations in space are closely related to those for generating targeting eye movements (saccades). However, the degree to which the voluntary deployment of attention to a location is necessarily accompanied by a corresponding saccade plan remains unclear. One problem is that attention and saccades are both automatically driven by salient sensory events; another is that the underlying processes unfold within tens of milliseconds only. Here, we use an urgent task design to resolve the evolution of a visuomotor choice on a moment-by-moment basis while independently controlling the endogenous (goal-driven) and exogenous (salience-driven) contributions to performance. Human participants saw a peripheral cue and, depending on its color, either looked at it (prosaccade) or looked at a diametrically opposite, uninformative non-cue (antisaccade). By varying the luminance of the stimuli, the exogenous contributions could be cleanly dissociated from the endogenous process guiding the choice over time. According to the measured timecourses, generating a correct antisaccade requires about 30 ms more processing time than generating a correct prosaccade based on the same perceptual signal. The results indicate that saccade plans are biased toward the location where attention is endogenously deployed, but the coupling is weak and can be willfully overridden very rapidly.

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

BACKGROUND: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development. METHODS: We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD). RESULTS: Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice. CONCLUSION: We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.

Exogenous capture accounts for fundamental differences between pro- and antisaccade performance.

To generate the next eye movement, oculomotor circuits take into consideration the physical salience of objects in view and current behavioral goals, exogenous and endogenous influences, respectively. However, the interactions between exogenous and endogenous mechanisms and their dynamic contributions to target selection have been difficult to resolve because they evolve extremely rapidly. In a recent study (Salinas et al., 2019), we achieved the necessary temporal precision using an urgent variant of the antisaccade task wherein motor plans are initiated early and choice accuracy depends sharply on when exactly the visual cue information becomes available. Empirical and modeling results indicated that the exogenous signal arrives ∼80 ms after cue onset and rapidly accelerates the (incorrect) plan toward the cue, whereas the informed endogenous signal arrives ∼25 ms later to favor the (correct) plan away from the cue. Here, we scrutinize a key mechanistic hypothesis about this dynamic, that the exogenous and endogenous signals act at different times and independently of each other. We test quantitative model predictions by comparing the performance of human participants instructed to look toward a visual cue or away from it under high urgency. We find that, indeed, the exogenous response is largely impervious to task instructions; it simply flips its sign relative to the correct choice, and this largely explains the drastic differences in psychometric performance between the two tasks. Thus, saccadic choices are strongly dictated by the alignment between salience and behavioral goals.

Long-term imaging of living adult zebrafish.

The zebrafish has become a widely used animal model due, in large part, to its accessibility to and usefulness for high-resolution optical imaging. Although zebrafish research has historically focused mostly on early development, in recent years the fish has increasingly been used to study regeneration, cancer metastasis, behavior and other processes taking place in juvenile and adult animals. However, imaging of live adult zebrafish is extremely challenging, with survival of adult fish limited to a few tens of minutes using standard imaging methods developed for zebrafish embryos and larvae. Here, we describe a new method for imaging intubated adult zebrafish using a specially designed 3D printed chamber for long-term imaging of adult zebrafish on inverted microscope systems. We demonstrate the utility of this new system by nearly day-long observation of neutrophil recruitment to a wound area in living double-transgenic adult casper zebrafish with fluorescently labeled neutrophils and lymphatic vessels, as well as intubating and imaging the same fish repeatedly. We also show that Mexican cavefish can be intubated and imaged in the same way, demonstrating this method can be used for long-term imaging of adult animals from diverse aquatic species.

Calcium State-Dependent Regulation of Epithelial Cell Quiescence by Stanniocalcin 1a.

The molecular mechanisms regulating cell quiescence-proliferation balance are not well defined. Using a zebrafish model, we report that Stc1a, a secreted glycoprotein, plays a key role in regulating the quiescence-proliferation balance of Ca2+ transporting epithelial cells (ionocytes). Zebrafish stc1a, but not the other stc genes, is expressed in a Ca2+ state-dependent manner. Genetic deletion of stc1a, but not stc2b, increased ionocyte proliferation, leading to elevated body Ca2+ levels, cardiac edema, body swelling, and premature death. The increased ionocyte proliferation was accompanied by an increase in the IGF1 receptor-mediated PI3 kinase-Akt-Tor signaling activity in ionocytes. Inhibition of the IGF1 receptor, PI3 kinase, Akt, and Tor signaling reduced ionocyte proliferation and rescued the edema and premature death in stc1a-/- fish, suggesting that Stc1a promotes ionocyte quiescence by suppressing local IGF signaling activity. Mechanistically, Stc1 acts by inhibiting Papp-aa, a zinc metalloproteinase degrading Igfbp5a. Inhibition of Papp-aa proteinase activity restored ionocyte quiescence-proliferation balance. Genetic deletion of papp-aa or its substrate igfbp5a in the stc1a-/- background reduced ionocyte proliferation and rescued the edema and premature death. These findings uncover a novel and Ca2+ state-dependent pathway regulating cell quiescence. Our findings also provide new insights into the importance of ionocyte quiescent-proliferation balance in organismal Ca2+ homeostasis and survival.

The metalloproteinase Papp-aa controls epithelial cell quiescence-proliferation transition.

Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.

Assessing the effectiveness of house-to-house visits on routine oral polio immunization completion and tracking of defaulters.

Strengthening routine immunization is one of the four prongs of the Global Polio Eradication Initiative. Using data collected through 30-cluster sample household surveys of caretakers of children aged 12-23 months, this paper assessed the effectiveness of house-to-house visits on routine oral polio immunization completion, using simple frequency tables, bivariate and multivariate logistic regression analyses. Logistic regression results demonstrated that children in households where the caregivers reported receiving a household visit by health workers were more likely to be fully immunized for polio through routine immunization than other children, although results were significant only after correcting for confounders. In Ethiopia and India, children of caregivers who remembered a house-to-house visit were significantly and positively associated with routine polio vaccination completion (OR = 2.2 and OR = 2.2 respectively). In Angola, the association was positive, though not significant (OR = 1.3). The evidence suggests that targeting high-risk areas for house-to-house visits played a role in increasing routine polio vaccination.

Gardening for the mental well-being of homeless women.

PURPOSE: To explore the perceptions of homeless women regarding their experience in a shelter-based garden project to promote mental wellness. Participants planted and tended the vegetable garden and prepared and ate the fruits of their labor. DESIGN: A qualitative descriptive design with a conventional content analysis of narrative data. METHOD: Data were gathered in semistructured interviews. Participants were homeless daytime shelter guests who had participated in at least eight gardening sessions over 4 weeks. The project was started in the fall of 2010 and the interviews were conducted over 2 months in the summer of 2011. FINDINGS: Two polarized themes were identified in the narratives, clustering around negative and positive thoughts. The "dark" theme centered on marginalization and the oppressiveness of shelter life. The "light" theme centered on stress relief, feeling socially included, and personal change. CONCLUSION: The gardening experience interrupted the participants' negative ruminations, offering stress relief and elements of social inclusion and self-actualization. Gardening is an inexpensive and positive intervention for a population with a high incidence of mental illness and distress.