Search

Abstract Background Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p

Summary: A wide variety of electrophilic derivatives of itaconate, the Kreb’s cycle-derived metabolite, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production. Endogenous itaconate directly targets cysteine 13 in IRAK4 (disrupting IRAK4 autophosphorylation and activation), drives the degradation of nuclear factor κB, and modulates global ubiquitination patterns. As a result, cells unable to make itaconate overproduce inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β in response to these innate activators. In contrast, the production of interferon (IFN)β, downstream of LPS, requires the production of itaconate. These data demonstrate that itaconate is a critical arbiter of inflammatory cytokine production downstream of multiple innate signaling pathways, laying the groundwork for the development of itaconate mimetics for the treatment of autoimmunity.

Purpose Patients with hepatocellular carcinoma (HCC) become refractory to repeated sessions of transarterial chemoembolization (TACE). The aim of this study was to identify predictors associated with overall survival and refractoriness following repetitive TACE of HCC among patients in Southeast Asia.

Background: Targeting interventions where most needed and effective is crucial for public health. Malaria control and elimination strategies increasingly rely on stratification to guide surveillance, to allocate vector control campaigns, and to prioritize access to community-based early diagnosis and treatment (EDT). We developed an original approach of dynamic clustering to improve local discrimination between heterogeneous malaria transmission settings. Methods: We analysed weekly malaria incidence records obtained from community-based EDT (malaria posts) in Karen/Kayin state, Myanmar. We smoothed longitudinal incidence series over multiple seasons using functional transformation. We regrouped village incidence series into clusters using a dynamic time warping clustering and compared them to the standard, 5-category annual incidence standard stratification. Results: We included 1115 villages from 2016 to 2020. We identified eleven P. falciparum and P. vivax incidence clusters which differed by amplitude, trends and seasonality. Specifically the 124 villages classified as “high transmission area” in the standard P. falciparum stratification belonged to the 11 distinct groups when accounting to inter-annual trends and intra-annual variations. Likewise for P. vivax, 399 “high transmission” villages actually corresponded to the 11 distinct dynamics. Conclusion: Our temporal dynamic clustering methodology is easy to implement and extracts more information than standard malaria stratification. Our method exploits longitudinal surveillance data to distinguish local dynamics, such as increasing inter-annual trends or seasonal differences, providing key information for decision-making. It is relevant to malaria strategies in other settings and to other diseases, especially when many countries deploy health information systems and collect increasing amounts of health outcome data. Funding: The Bill & Melinda Gates Foundation, The Global Fund against AIDS, Tuberculosis and Malaria (the Regional Artemisinin Initiative) and the Wellcome Trust funded the METF program.

Abstract Background The collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance. Methods This retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time. Results In the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard. Conclusions Surveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.

Abstract Background Providing at-risk communities with uninterrupted access to early diagnosis and treatment is a key component in reducing malaria transmission and achieving elimination. As programmes approach malaria elimination targets it is critical that each case is tested and treated early, which may present a challenge when the burden of malaria is reduced. In this paper we investigate whether malaria testing rates decline over time and assess the impacts of integrating malaria and non-malaria services on testing rates in the malaria elimination task force (METF) programme in the Kayin state of Myanmar. Methods A retrospective analysis was conducted using weekly collected data on testing rates from a network of more than 1200 malaria posts during the period from 2014 to 2020. To determine whether monthly testing rates changed over the years of programme operations, and whether integrating malaria and non-malaria services impacted these testing rates, we fitted negative binomial mixed-effects regression models to aggregate monthly data, accounting for malaria seasonal variation. Results In the first year of malaria post operation, testing rates declined, correlating with a decline in attendance by people from outside the malaria post catchment area, but then remained fairly constant (the Rate Ratio (RR) for 2nd versus 1st year open ranged from 0.68 to 0.84 across the four townships included in the analysis, the RR for 3rd to 6th year versus 1st year open were similar, ranging from 0.59–0.78). The implementation of a training programme, which was intended to expand the role of the malaria post workers, had minimal impact on testing rates up to 24 months after training was delivered (RR for integrated versus malaria-only services ranged from 1.00 to 1.07 across METF townships). Conclusion Despite the decline in malaria incidence from 2014 to 2020, there has been no decline in the malaria testing rate in the METF programme after the establishment of the complete malaria post network in 2016. While the integration of malaria posts with other health services provides benefits to the population, our evaluation questions the necessity of integrated services in maintaining malaria testing rates in areas approaching elimination of malaria.

Abstract Theta-burst stimulation (TBS) is a form of non-invasive neuromodulation which is delivered in an intermittent (iTBS) or continuous (cTBS) manner. Although 600 pulses is the most common dose, the goal of these experiments was to evaluate the effect of higher per-dose pulse numbers on cortical excitability. Sixty individuals were recruited for 2 experiments. In Experiment 1, participants received 600, 1200, 1800, or sham (600) iTBS (4 visits, counterbalanced, left motor cortex, 80% active threshold). In Experiment 2, participants received 600, 1200, 1800, 3600, or sham (600) cTBS (5 visits, counterbalanced). Motor evoked potentials (MEP) were measured in 10-min increments for 60 min. For iTBS, there was a significant interaction between dose and time (F = 3.8296, p = 0.01), driven by iTBS (1200) which decreased excitability for up to 50 min (t = 3.1267, p = 0.001). For cTBS, there was no overall interaction between dose and time (F = 1.1513, p = 0.33). Relative to sham, cTBS (3600) increased excitability for up to 60 min (t = 2.0880, p = 0.04). There were no other significant effects of dose relative to sham in either experiment. Secondary analyses revealed high within and between subject variability. These results suggest that iTBS (1200) and cTBS (3600) are, respectively, the most effective doses for decreasing and increasing cortical excitability.

Abstract Background Improving access to early diagnosis and treatment (EDT) has increasingly proven to be a major contributor to decreasing malaria incidence in low-transmission settings. The Malaria Elimination Task Force (METF) has deployed malaria posts set up in Eastern Myanmar, providing free uninterrupted community-based access to EDT in more than 1200 villages. Ensuring high quality services are provided by these malaria posts is essential to reaching elimination targets. The present study aimed to determine the functionality of the malaria posts in the METF programme. Methods This report analysed routinely collected data (weekly reports, individual consultation, diagnostic test quality control) and data collected specifically during monitoring and evaluation visits using descriptive statistics and univariate logistic regression. The presence of major dysfunctions (stock-outs and reported closing; likely to impair the ability of the population to access EDT) or minor dysfunctions (no formal METF training, lack of regular salary, forms and manual not on-site, and low frequency of supervisor visits) and the ability to anticipate dysfunctions through analysis of weekly reports were assessed. Results A total of 65% of malaria posts had no major dysfunction identified during monitoring and evaluation visits, while 86% of malaria posts were fully stocked with tests and medicines used for treatment. Diagnosis was correctly conducted with few false positives and rare mis-speciation of results. Malaria post worker knowledge of malaria treatments showed few gaps, mostly in the treatment of more complex presentations. Malaria posts were well utilized in the population, with 94% of consultations occurring within the first 3 days of fever. In the regression analysis, reported stock-outs and delayed weekly reports were associated with observed major and minor dysfunctions in monitoring and evaluation visits, emphasizing the need to reinforce support to malaria post supervisors, who were responsible for the local logistics of supply and data transmission and day-to-day supervision. Conclusion The malaria posts operating under the METF programme perform to a high standard, with the majority offering uninterrupted access to diagnosis and treatment, and high service uptake in the villages serviced by the programme. However, programme operations can be strengthened by increasing malaria post supervisor visits and re-training malaria post workers.

Summary: Classical activation of macrophages (M(LPS+IFNγ)) elicits the expression of inducible nitric oxide synthase (iNOS), generating large amounts of NO and inhibiting mitochondrial respiration. Upregulation of glycolysis and a disrupted tricarboxylic acid (TCA) cycle underpin this switch to a pro-inflammatory phenotype. We show that the NOS cofactor tetrahydrobiopterin (BH4) modulates IL-1β production and key aspects of metabolic remodeling in activated murine macrophages via NO production. Using two complementary genetic models, we reveal that NO modulates levels of the essential TCA cycle metabolites citrate and succinate, as well as the inflammatory mediator itaconate. Furthermore, NO regulates macrophage respiratory function via changes in the abundance of critical N-module subunits in Complex I. However, NO-deficient cells can still upregulate glycolysis despite changes in the abundance of glycolytic intermediates and proteins involved in glucose metabolism. Our findings reveal a fundamental role for iNOS-derived NO in regulating metabolic remodeling and cytokine production in the pro-inflammatory macrophage. : Metabolic remodeling underpins inflammatory macrophage activation, but the modulatory mechanisms are still being elucidated. Bailey et al. show that NO regulates specific changes in the abundance of TCA cycle metabolites, itaconate, and catalytic subunits of Complex I in the respiratory chain in inflammatory murine macrophages both in vitro and in vivo. Keywords: macrophage metabolism, immunometabolism, tetrahydrobiopterin, nitric oxide, mitochondria, inflammation

BackgroundThe collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance.MethodsThis retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time.ResultsIn the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard.ConclusionsSurveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.

The purpose of this study was to determine the financial experiences of pre-service teachers in handling finances. The study used a qualitative design and focused on fourth-year BEED students at Holy Trinity College in General Santos City, Philippines. Ten participants were chosen by random sampling, and data were collected using a semi-structured interview guide. The data were then analyzed thematically. The study emphasized that pre-service teachers experiences in handling their finances are categorized into three major themes: Adjusted Habits, Proper Budgeting, and Part-Time Jobs. Pre-service teachers prepared for the future by prioritizing essentials and changing their habits. Pre-service teachers are generally known for their frugality and good financial management because it means overcoming the need to purchase the things you like, maintaining financial self-discipline can be difficult. Due to a lack of resources, teachers must be more imaginative and innovative in order to provide students with helpful instructional resources and alternative methods for delivering lessons that are effective. According to the recommendations, pre-service teachers have to get guidance and assistance with money management. Additionally, by training future pre-teachers and sharing their own experiences, experienced teachers should help pre-service and future educators. [ABSTRACT FROM AUTHOR]

Author(s): Jade D. Stafford [sup.1] , Emily R. Goggins [sup.1] , Eva Lathrop [sup.1] , Lisa B. Haddad [sup.1] Author Affiliations: (1) grid.189967.8, 0000 0001 0941 6502, Department of Obstetrics [...], Objectives Many studies correlate lower health literacy with poorer health outcomes and inferior provider-patient communication. Little is known about how impaired health literacy among women receiving prenatal care at inner city public hospitals may impact reproductive health behaviors and outcomes. The objective of this study was to assess health literacy among postpartum women receiving care at a public tertiary care center and to explore the association of impaired health literacy with prenatal care attendance and postpartum outcomes. Methods Written consent was obtained before completing the 7-item REALM-SF study tool to assess health literacy. A score of zero to three indicated low health literacy, four to six moderately low health literacy, and seven adequate health literacy. Patients completed a 25-item demographic questionnaire, and medical outcomes were obtained via this questionnaire and chart review. Descriptive statistics were generated, and bivariate and multivariate analyses evaluated the association between REALM-SF score and study outcomes. Results We recruited 300 adult English-speaking postpartum women and 293 were included in the final analysis. The majority of participants (53.9%) experienced impaired health literacy (score zero to six). Most respondents completed high school or higher education (77.1%), 17.8% had no prenatal care, and 83.6% reported that this pregnancy was unplanned. After adjusting for age, race, and education, women in the lowest health literacy group were less likely to indicate a plan to exclusively breastfeed (aRR = 0.54, p = 0.03). Conclusions for Practice Impaired health literacy affects a majority of our patients and is associated with reproductive health outcomes, including exclusive breastfeeding. Health care providers should attempt to overcome differences in health literacy through strong breastfeeding promotion. Verbal and written patient education materials should be tailored to the needs of patients with impaired health literacy.

Purpose Patients with hepatocellular carcinoma (HCC) become refractory to repeated sessions of transarterial chemoembolization (TACE). The aim of this study was to identify predictors associated with overall survival and refractoriness following repetitive TACE of HCC among patients in Southeast Asia. Methods The clinical and laboratory characteristics and radiologic response of 39 patients treated with conventional TACE (range 2 to 5) with mitomycin from January 2012 to June 2018 were retrospectively analyzed. Patients were mostly male with a median age of 59 years and belonged to the BCLC B stage with a median tumor size of 7.5 cm. Results The median overall survival was 23.2 months and the overall mortality at 5 years was 36%. Multivariate Cox regression analysis revealed that Child–Pugh (CP) score (hazard ratio [HR] = 3.47, p = 0.044), AST (HR = 7.6, p = 0.021), tumor size (HR = 5.47, p = 0.033), progressive disease on Choi criteria (HR = 5.47, confidence interval [CI] 1.15–25.99, p = 0.033), neutrophil-lymphocyte ratio (HR = 1.25, p = 0.049), and nodular enhancement on follow-up computed tomography (CT; HR = 1.98, p = 0.034) were independent risk factors for poor survival. ALT (p = 0.005), enhancement (p = 0.003), CP score (p = 0.010), and progressive disease on Choi criteria (p = 0.022) were predictive of TACE refractoriness/failure. Conclusion Elevated liver enzymes, CP score, and progressive disease on Choi criteria accurately predict TACE refractoriness and failure, allowing early identification of patients who might benefit from other therapies. [ABSTRACT FROM AUTHOR]

Cyberbullying has long been a concern of youth advocates which number around increased mainly due to too much spending on the social media platform. Recently, it has dominated the headlines as a major current-day adolescent challenge. This paper examined the perceptions of cyberbullied student-victims in cyberbullying and their life satisfaction. A descriptive survey research design was utilized in this study using the two modified survey questionnaires from Olweus and Huebuer et al. Results revealed that 70% of cyberbullied student-victims experienced bullying on Facebook/messenger. It also showed that the majority of them (58%) that their friends were their trusted persons to talk about their cyberbullying experiences. In conclusion, student-victims have negative experiences in cyberbullying which it gives an impact that they were equally satisfied and dissatisfied with their life but mostly satisfied with their residency due to their family who made them feel safe and loved. [ABSTRACT FROM AUTHOR]

Sulfate- and sulfite-reducing bacteria (SRB) are a group of strict anaerobes found within the human gut. Bilophila wadsworthia, a sulfite-reducing bacterium which produces hydrogen sulfide (H2S) from taurine and isethionate respiration, is a common member of the healthy commensal human gut microbiota but has been implicated in several disease states including inflammatory bowel disease and colorectal cancer. Bacteroides thetaiotaomicron, one of the most prominent gut bacteria, has sulfatases which release sulfate, serving as a potential substrate for sulfate-reducing bacteria. Here, we showed that when B. thetaiotaomicron and B. wadsworthia were in co-culture, there was a significant increase in B. thetaiotaomicron’s growth and in H2S production by B. wadsworthia. Differential gene expression analysis revealed increased expression of B. wadsworthia’s dsrMKJOP complex in co-culture, which delivers electrons for sulfite reduction to H2S. This was accompanied by a decreased expression of genes associated with taurine, sulfolactate, and thiosulfate respiration, indicating that B. thetaiotaomicron may provide an alternative source of sulfite to B. wadsworthia. We hypothesized adenosine 5’-phosphosulfate (APS) to be this intermediate. Indeed, B. wadsworthia was able to grow using APS or sulfite as electron acceptors. Endometabolomic and transcriptomic analyses revealed decreased production of indole by B. thetaiotaomicron in co-culture with B. wadsworthia due to enhanced tryptophan utilization by B. wadsworthia. The results of this microbe−microbe interaction could have significant pro-inflammatory effects in the human gut environment.

The Canadian province of Nova Scotia recently became the first North American jurisdiction to implement deemed consent for deceased organ donation as part of a comprehensive legislative reform of their donation and transplantation system. This study will examine the performance metrics and effectiveness of this policy in comparison with other Canadian provinces via a natural experiment evaluation. We will use a cross-sectional controlled interrupted time series quasi-experimental design. Our primary outcome will be consent for deceased donation as confirmed at the time of eligibility (prior registered intent to donate will be noted but not be considered positive unless affirmed at the time of eligibility). Secondary outcomes will include identification and referral of patients who are potential donors, rates of family override of previously registered intent to donate, and donation and transplantation rates per million population. Data will be collected from potential donor audits in Nova Scotia and 3 control provinces (provinces in Canada without deemed consent policies). Study outcomes will be compared in Nova Scotia relative to control provinces in the 3 y before and 3 y after the implementation of legislative reform. These provinces were selected as having systems resembling those of Nova Scotia but without deemed consent.Using controlled interrupted time series methodology compared with other Canadian provinces with otherwise similar systems, we aim to isolate the impact of the deemed consent aspect of legislative reform in Nova Scotia using a robust natural experiment evaluation design as much as possible. Careful selection of outcome measures will allow donation and transplantation stakeholders to properly evaluate if similar reforms should be considered in their jurisdictions.