Improving Mental Health Literacy and Reducing Psychological Problems Among Teachers in Zambia: Protocol for Implementation and Evaluation of a Wellness4Teachers Email Messaging Program.

BACKGROUND: Primary, basic, secondary, and high school teachers are constantly faced with increased work stressors that can result in psychological health challenges such as burnout, anxiety, and depression, and in some cases, physical health problems. It is presently unknown what the mental health literacy levels are or the prevalence and correlates of psychological issues among teachers in Zambia. It is also unknown if an email mental messaging program (Wellness4Teachers) would effectively reduce burnout and associated psychological problems and improve mental health literacy among teachers. OBJECTIVE: The primary objectives of this study are to determine if daily supportive email messages plus weekly mental health literacy information delivered via email can help improve mental health literacy and reduce the prevalence of moderate to high stress symptoms, burnout, moderate to high anxiety symptoms, moderate to high depression symptoms, and low resilience among school teachers in Zambia. The secondary objectives of this study are to evaluate the baseline prevalence and correlates of moderate to high stress, burnout, moderate to high anxiety, moderate to high depression, and low resilience among school teachers in Zambia. METHODS: This is a quantitative longitudinal and cross-sessional study. Data will be collected at the baseline (the onset of the program), 6 weeks, 3 months, 6 months (the program midpoint), and 12 months (the end point) using web-based surveys. Individual teachers will subscribe by accepting an invitation to do so from the Lusaka Apex Medical University organizational account on the ResilienceNHope web-based application. Data will be analyzed using SPSS version 25 with descriptive and inferential statistics. Outcome measures will be evaluated using standardized rating scales. RESULTS: The Wellness4Teachers email program is expected to improve the participating teachers' mental health literacy and well-being. It is anticipated that the prevalence of stress, burnout, anxiety, depression, and low resilience among teachers in Zambia will be similar to those reported in other jurisdictions. In addition, it is expected that demographic, socioeconomic, and organizational factors, class size, and grade teaching will be associated with burnout and other psychological disorders among teachers, as indicated in the literature. Results are expected 2 years after the program's launch. CONCLUSIONS: The Wellness4Teachers email program will provide essential insight into the prevalence and correlates of psychological problems among teachers in Zambia and the program's impact on subscribers' mental health literacy and well-being. The outcome of this study will help inform policy and decision-making regarding psychological interventions for teachers in Zambia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44370.

Labour and delivery ward register data availability, quality, and utility - Every Newborn - birth indicators research tracking in hospitals (EN-BIRTH) study baseline analysis in three countries.

BACKGROUND: Countries with the highest burden of maternal and newborn deaths and stillbirths often have little information on these deaths. Since over 81% of births worldwide now occur in facilities, using routine facility data could reduce this data gap. We assessed the availability, quality, and utility of routine labour and delivery ward register data in five hospitals in Bangladesh, Nepal, and Tanzania. This paper forms the baseline register assessment for the Every Newborn-Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study. METHODS: We extracted 21 data elements from routine hospital labour ward registers, useful to calculate selected maternal and newborn health (MNH) indicators. The study sites were five public hospitals during a one-year period (2016-17). We measured 1) availability: completeness of data elements by register design, 2) data quality: implausibility, internal consistency, and heaping of birthweight and explored 3) utility by calculating selected MNH indicators using the available data. RESULTS: Data were extracted for 20,075 births. Register design was different between the five hospitals with 10-17 of the 21 selected MNH data elements available. More data were available for health outcomes than interventions. Nearly all available data elements were > 95% complete in four of the five hospitals and implausible values were rare. Data elements captured in specific columns were 85.2% highly complete compared to 25.0% captured in non-specific columns. Birthweight data were less complete for stillbirths than live births at two hospitals, and significant heaping was found in all sites, especially at 2500g and 3000g. All five hospitals recorded count data required to calculate impact indicators including; stillbirth rate, low birthweight rate, Caesarean section rate, and mortality rates. CONCLUSIONS: Data needed to calculate MNH indicators are mostly available and highly complete in EN-BIRTH study hospital routine labour ward registers in Bangladesh, Nepal and Tanzania. Register designs need to include interventions for coverage measurement. There is potential to improve data quality if Health Management Information Systems utilization with feedback loops can be strengthened. Routine health facility data could contribute to reduce the coverage and impact data gap around the time of birth.

Prevalence and factors associated with antenatal depressive symptoms among women enrolled in Option B+ antenatal HIV care in Malawi: a cross-sectional analysis.

BACKGROUND: Option B+ has increased the number of pregnant women initiating antiretroviral therapy for HIV, yet retention in HIV care is sub-optimal. Retention may be affected by antenatal depression. However, few data exist on antenatal depression in this population. AIM: Describe the prevalence and factors associated with antenatal depression among Malawian women enrolled in Option B+. METHOD: At their first antenatal visit, women with HIV provided demographic and psychosocial information, including depression as measured with the locally validated Edinburgh Postnatal Depression Scale (EPDS). Prevalence ratios (PR) for factors associated with probable depression (EPDS ≥6) were estimated with log binomial regression. RESULTS: 9.5% (95% CI: 7.5-11.9%) of women screened positive for current depression, and 46% self-reported a history of depression or anxiety. Women were more likely to screen positive for current depression if they reported a history of depression (adjusted PR: 2.42; 95% CI: 1.48-3.95) or had ever experienced intimate partner violence (1.77; 1.11-2.81). Having an unintended current pregnancy (1.78; 0.99-3.21), being unmarried (1.66; 0.97-2.84), or employed (1.56; 1.00-2.44) had potential associations with probable depression. CONCLUSIONS: Probable antenatal depression affected a notable proportion of women living with HIV, comparable to other global regions. Screening for antenatal depression in HIV care should be considered.

Optimizing prevention of HIV mother to child transmission: Duration of antiretroviral therapy and viral suppression at delivery among pregnant Malawian women.

BACKGROUND: Effective antiretroviral therapy during pregnancy minimizes the risk of vertical HIV transmission. Some women present late in their pregnancy for first antenatal visit; whether these women achieve viral suppression by delivery and how suppression varies with time on ART is unclear. METHODS: We conducted a prospective cohort study of HIV-infected pregnant women initiating antiretroviral therapy for the first time at Bwaila Hospital in Lilongwe, Malawi from June 2015 to November 2016. Multivariable Poisson models with robust variance estimators were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of the association between duration of ART and both viral load (VL) ≥1000 copies/ml and VL ≥40 copies/ml at delivery. RESULTS: Of the 252 women who had viral load testing at delivery, 40 (16%) and 78 (31%) had VL ≥1000 copies/ml and VL ≥40 copies/ml, respectively. The proportion of women with poor adherence to ART was higher among women who were on ART for ≤12 weeks (9/50 = 18.0%) than among those who were on ART for 13-35 weeks (18/194 = 9.3%). Compared to women who were on ART for ≤12 weeks, women who were on ART for 13-20 weeks (RR = 0.52; 95% CI: 0.36-0.74) or 21-35 weeks (RR = 0.26; 95% CI: 0.14-0.48) had a lower risk of VL ≥40 copies/ml at delivery. Similar comparisons for VL ≥1000 copies/ml at delivery showed decrease in risk although not significant for those on ART 13-20 weeks. CONCLUSION: Longer duration of ART during pregnancy was associated with suppressed viral load at delivery. Early ANC attendance in pregnancy to facilitate prompt ART initiation for HIV-positive women is essential in the effort to eliminate HIV vertical transmission.

Predicting changes of reaction networks with partial kinetic information.

We wish to predict changes of reaction networks with partial kinetic information that lead to target changes of their steady states. The changes may be either increases or decreases of influxes, reaction knockouts, or multiple changes of these two kinds. Our prime applications are knockout prediction tasks for metabolic and regulation networks. In a first step, we propose a formal modeling language for reaction networks with partial kinetic information. The modeling language has a graphical syntax reminiscent to Petri nets. Each reaction in a model comes with a partial description of its kinetics, based on a similarity relation on kinetic functions that we introduce. Such partial descriptions are able to model the regulation of existing metabolic networks for which precise kinetic knowledge is usually not available. In a second step, we develop prediction algorithms that can be applied to any reaction network modeled in our language. These algorithms perform qualitative reasoning based on abstract interpretation, by which the kinetic unknowns are abstracted away. Given a reaction network, abstract interpretation produces a finite domain constraint in a novel class. We show how to solve these finite domain constraints with an existing finite domain constraint solver, and how to interpret the solution sets as predictions of multiple reaction knockouts that lead to a desired change of the steady states. We have implemented the prediction algorithm and integrated it into a prediction tool. This journal article extends the two conference papers John et al. (2013) and Niehren et al. (2015) while adding a new prediction algorithm for multiple gene knockouts. An application to single gene knockout prediction for surfactin overproduction was presented in Coutte et al. (2015). It illustrates the adequacy of the model-based predictions made by our algorithm in the wet lab.

Modeling leucine's metabolic pathway and knockout prediction improving the production of surfactin, a biosurfactant from Bacillus subtilis.

A Bacillus subtilis mutant strain overexpressing surfactin biosynthetic genes was previously constructed. In order to further increase the production of this biosurfactant, our hypothesis is that the surfactin precursors, especially leucine, must be overproduced. We present a three step approach for leucine overproduction directed by methods from computational biology. Firstly, we develop a new algorithm for gene knockout prediction based on abstract interpretation, which applies to a recent modeling language for reaction networks with partial kinetic information. Secondly, we model the leucine metabolic pathway as a reaction network in this language, and apply the knockout prediction algorithm with the target of leucine overproduction. Out of the 21 reactions corresponding to potential gene knockouts, the prediction algorithm selects 12 reactions. Six knockouts were introduced in B. subtilis 168 derivatives strains to verify their effects on surfactin production. For all generated mutants, the specific surfactin production is increased from 1.6- to 20.9-fold during the exponential growth phase, depending on the medium composition. These results show the effectiveness of the knockout prediction approach based on formal models for metabolic reaction networks with partial kinetic information, and confirms our hypothesis that precursors supply is one of the main parameters to optimize surfactin overproduction.

Elucidating the sources of ß-catenin dynamics in human neural progenitor cells.

Human neural progenitor cells (hNPCs) form a new prospect for replacement therapies in the context of neurodegenerative diseases. The Wnt/ß-catenin signaling pathway is known to be involved in the differentiation process of hNPCs. RVM cells form a common cell model of hNPCs for in vitro investigation. Previous observations in RVM cells raise the question of whether observed kinetics of the Wnt/ß-catenin pathway in later differentiation phases are subject to self-induced signaling. However, a concern when investigating RVM cells is that experimental results are possibly biased by the asynchrony of cells w.r.t. the cell cycle. In this paper, we present, based on experimental data, a computational modeling study on the Wnt/ß-catenin signaling pathway in RVM cell populations asynchronously distributed w.r.t. to their cell cycle phases. Therefore, we derive a stochastic model of the pathway in single cells from the reference model in literature and extend it by means of cell populations and cell cycle asynchrony. Based on this, we show that the impact of the cell cycle asynchrony on wet-lab results that average over cell populations is negligible. We then further extend our model and the thus-obtained simulation results provide additional evidence that self-induced Wnt signaling occurs in RVM cells. We further report on significant stochastic effects that directly result from model parameters provided in literature and contradict experimental observations.

Initial receptor-ligand interactions modulate gene expression and phagosomal properties during both early and late stages of phagocytosis.

The receptors engaged during recognition and phagocytic uptake of microorganisms and particles influence signaling events and diverse subcellular responses that occur during phagosome formation and maturation. However, pathogens generally have multiple ligands on their surface, making it difficult to dissect the roles of individual receptors during phagocytosis. Moreover, it remains elusive to which extent receptor-ligand interactions and early binding events define the subsequent intracellular fate of phagosomes. Here, we used latex beads coupled to single ligands, focusing on immunoglobulin G, mannan, bacterial lipopolysaccharides and avidin, and monitored: (1) phagocytic uptake rates, (2) fusion of phagosomes with lysosomal compartments, (3) the gene expression profile during phagocytosis, (4) the protein composition of mature phagosomes and (5) time-dependent dynamics of protein association with phagosomes in J774.A1 mouse macrophages. The differently coated latex beads were internalized at different rates and exhibited different kinetics of phagolysosomal fusion events dependent on their specific ligand. Furthermore, less than 60% of identified phagosomal proteins and only 10-15% of changes in gene expression were common to all investigated ligands. These findings demonstrate that each single ligand induced a distinct pattern of genes and a different protein composition of phagosomes. Taken together, our data argue that phagocytic receptor-specific programs of signaling events direct phagosomes to different physiological states and support the existence of a specific receptor-ligand 'signature' during the whole process of phagocytosis.

RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent antiviral strategy.

We describe the design and characterization of a potent human respiratory syncytial virus (RSV) nucleocapsid gene-specific small interfering RNA (siRNA), ALN-RSV01. In in vitro RSV plaque assays, ALN-RSV01 showed a 50% inhibitory concentration of 0.7 nM. Sequence analysis of primary isolates of RSV showed that the siRNA target site was absolutely conserved in 89/95 isolates, and ALN-RSV01 demonstrated activity against all isolates, including those with single-mismatch mutations. In vivo, intranasal dosing of ALN-RSV01 in a BALB/c mouse model resulted in potent antiviral efficacy, with 2.5- to 3.0-log-unit reductions in RSV lung concentrations being achieved when ALN-RSV01 was administered prophylactically or therapeutically in both single-dose and multidose regimens. The specificity of ALN-RSV01 was demonstrated in vivo by using mismatch controls; and the absence of an immune stimulatory mechanism was demonstrated by showing that nonspecific siRNAs that induce alpha interferon and tumor necrosis factor alpha lack antiviral efficacy, while a chemically modified form of ALN-RSV01 lacking measurable immunostimulatory capacity retained full activity in vivo. Furthermore, an RNA interference mechanism of action was demonstrated by the capture of the site-specific cleavage product of the RSV mRNA via rapid amplification of cDNA ends both in vitro and in vivo. These studies lay a solid foundation for the further investigation of ALN-RSV01 as a novel therapeutic antiviral agent for clinical use by humans.