Continuous distribution of insecticide-treated nets (ITNs) has now been accepted as one way of sustaining ITN universal coverage. Community-based channels offer an interesting means of delivering ...ITNs to households to sustain universal ITN coverage. The objective of this study was to provide proof of concept for this channel.
A 9-month, community-based, distribution pilot was implemented beginning 1 year after a mass campaign in Lainya County, South Sudan from 2012 to 2013. Following social mobilization, community members could request an ITN from a net coupon holder. Eligibility criteria included having lost an ITN, giving birth outside of the health facility, or not having enough ITNs for all household members. After verification, households could exchange the coupon for an ITN at a distribution point. The evaluation was a pre/post design using representative household surveys with two-stage cluster sampling and a sample size of 600 households per survey.
At endline, 78% of respondents were aware of the scheme and 89% of those also received an ITN through community-based distribution. Population access to ITNs nearly doubled, from 38% at baseline to 66% after the pilot. Household ownership of any ITN and enough ITNs (1 for 2 people) also increased significantly, from 66 to 82% and 19 to 46%, respectively. Community-based distribution was the only source of ITNs for 53.4% of households. The proportion of the population using an ITN last night increased from 22.7% at baseline to 53.9% at endline. A logistic regression model indicates that although behaviour change communication was positively associated with an increase in ITN use, access to enough nets was the greatest determinant of use.
ITN access and use improved significantly in the study area during the pilot, coming close to universal coverage targets. This pilot serves as proof of concept for the community-based distribution methodology implemented as a mechanism to sustain ITN universal coverage. Longer periods of implementation should be evaluated to determine whether community-based distribution can successfully maintain ITN coverage beyond the short term, and reach all wealth quintiles equitably.
Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of ...maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy.
Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data.
LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of $449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered.
The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency.
Insecticide-treated nets are a key intervention for malaria prevention. While mass distribution can rapidly scale up ITN coverage, multiple channels may be needed to sustain high levels of ITN access ...and ownership. In Ghana's Eastern Region, a continuous ITN distribution pilot, started in October 2012, 18-24 months after a mass campaign. The pilot distributed ITNs through antenatal care services (ANC), child welfare clinic services (CWC) through the Expanded Programme on Immunization, and to students in two classes of primary schools.
ITN ownership and access were evaluated through two cross-sectional surveys, conducted at baseline in April 2012, 11-15 months after the mass campaign, and at endline in December 2013, after 1 year of continuous distribution. A representative sample was obtained using a multi-stage cluster sampling design. Household heads were interviewed using a structured questionnaire.
Household ownership of at least one ITN was 91.3% (95% CI 88.8-93.9) at baseline and was not statistically significant at endline 18 months later at 88.3% (95% CI 84.9-91.0) (p = 0.10). Ownership of at least 1 ITN per two people significantly decreased from 51.3% (95% CI 47.1-55.4) to 40.2% (95% CI 36.4-44.6) (p < 0.01). Population access to an ITN within the household also significantly decreased from 74.5% (95% CI 71.2-77.7) at baseline to 66.4% (95% CI 62.9-69.9) at endline (p < 0.01). The concentration index score for any CD channel was slightly positive (0.10; 95% CI 0.04-0.15).
Thirty-one months after the mass campaign, the 15 months of continuous distribution activities had maintained levels of household ownership at least one ITN, but household ownership of one ITN for every two people and population access to ITN had declined. Ownership and access were higher with the CD programme than without. However, the number of ITNs delivered via ANC, CWC and two primary school classes were insufficient to sustain coverage targets. Future programmes should implement continuous distribution strategies fully within 1 year after a campaign or widen eligibility criteria (such as increase the number of classes) during the first year of implementation to make up for programme delays.
Continuous distribution of insecticide-treated nets (ITNs) is thought to be an effective mechanism to maintain ITN ownership and access between or in the absence of mass campaigns, but evidence is ...limited. A community-based ITN distribution pilot was implemented and evaluated in Toamasina II District, Madagascar, to assess this new channel for continuous ITN distribution.
Beginning 9 months after the December 2012 mass campaign, a community-based distribution pilot ran for an additional 9 months, from September 2013 to June 2014. Households requested ITN coupons from community agents in their village. After verification by the agents, households exchanged the coupon for an ITN at a distribution point. The evaluation was a two-stage cluster survey with a sample size of 1125 households. Counterfactual ITN ownership and access were calculated by excluding ITNs received through the community pilot.
At the end of the pilot, household ownership of any ITN was 96.5%, population access to ITN was 81.5 and 61.5% of households owned at least 1 ITN for every 2 people. Without the ITNs provided through the community channel, household ownership of any ITN was estimated at 74.6%, population access to an ITN at 55.5%, and households that owned at least 1 ITN for 2 people at only 34.7%, 18 months after the 2012 campaign. Ownership of community-distributed ITNs was higher among the poorest wealth quintiles. Over 80% of respondents felt the community scheme was fair and simple to use.
Household ITN ownership and population ITN access exceeded RBM targets after the 9-month community distribution pilot. The pilot successfully provided coupons and ITNs to households requesting them, particularly for the least poor wealth quintiles, and the scheme was well-perceived by communities. Further research is needed to determine whether community-based distribution can sustain ITN ownership and access over the long term, how continuous availability of ITNs affects household net replacement behaviour, and whether community-based distribution is cost-effective when combined with mass campaigns, or if used with other continuous channels instead of mass campaigns.
Background
Microglia, the resident brain immune cells, play a critical role in brain homeostasis and disease progression. In neurodegenerative conditions, microglia acquire the neurodegenerative ...phenotype (MGnD), whose function is poorly understood. MicroRNA‐155 (miR‐155), enriched in immune cells, critically regulates MGnD. However, its role in Alzheimer’s disease (AD) pathogenesis remains unclear.
Methods
We used RNAseq and immunohistochemistry (n = 6‐8 per sex per group) to investigate the gene expression profile and AD pathology. We further utilized single‐cell RNAseq (n = 5 per group) to identify microglial clusters. Whole‐tissue proteomics (n = 4) was applied to detect the protein changes in brain milieu. Moreover, we used spontaneous alternation and forced alternation tests to evaluate the cognition (n = 33‐36).
Result
We report that microglial deletion of miR‐155 induces a pre‐MGnD activation state via interferon‐g (IFNg) signaling and blocking IFNg signaling attenuates MGnD induction and microglial phagocytosis. Single‐cell RNAseq analysis of microglia from AD mouse model identifies Stat1 and Clec2d as pre‐MGnD markers. This phenotypic transition enhances amyloid plaque compaction, reduces dystrophic neurites, attenuates plaque‐associated synaptic degradation, and improves cognition.
Conclusion
Our study demonstrates a novel miR‐155‐mediated regulatory mechanism of MGnD and the beneficial role of IFNg‐responsive pre‐MGnD in restricting neurodegenerative pathology and preserving cognitive function in an AD mouse model, highlighting miR‐155 and IFNg as potential therapeutic targets for AD.
High on-clopidogrel platelet reactivity (HPR) associates with ischemic risk in patients after percutaneous intervention (PCI). This study aimed to evaluate the association of HPR as assessed by ...multiple electrode aggregometry (MEA) with ischemic, thromboembolic, and bleeding risk in patients with atrial fibrillation (AF) undergoing PCI. Patients with AF and an indication for oral anticoagulation (OAC) were included in this prospective cohort study on day 1–3 after PCI. Platelet aggregation U was analyzed by MEA. HPR and low platelet reactivity (LPR) were defined as ADP-induced aggregation ≥ 46 U and ≤ 18 U, respectively. TRAP-6-induced aggregation reference was 94–156 U. The primary outcome was time to all-cause death, myocardial infarction, or stroke at 6 months. The secondary outcome was time to non-major clinically relevant bleedings or major bleedings. 159 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range 72–82) and 111 (70%) were male. Median ADP- and TRAP-induced aggregation were 12 (6–17) and 49 (35–68) U, respectively. 147 (93%) patients had a low overall aggregability. HPR was detected in 2 patients (1%) and 125 (79%) had LPR. ADP-induced aggregation did not significantly associate with the primary outcome (r = 0.081, p = 0.309) but correlated inversely with bleeding risk (r = − 0.201, p = 0.011). HPR status as assessed by MEA among patients with AF after PCI was rare and overall aggregability was low. Conventional cut-off values for HPR might be inappropriate for these patients. ADP-induced aggregation might be helpful to identify patients at risk for bleeding.
While some data on net durability have been accumulating in recent years, including formative qualitative research on attitudes towards net care and repair, no data are available on how the ...durability of a net is influenced by behaviour of net maintenance, care and repair, and whether behavioural change interventions (BCC) could substantially impact on the average useful life of the net.
The study used an intervention-control design with before-after assessment through repeated cross-sectional household surveys with two-stage cluster sampling following Nasarawa State's December 2010 mass campaign. All campaign nets were 100-denier polyester, long-lasting insecticidal nets (LLIN). Baseline, midline, and endline surveys occurred at one-year intervals, in March 2012, March 2013, and April 2014, respectively. Outcome measures were the proportion of confirmed campaign nets with observed repairs, and the proportion in serviceable condition, measured with proportionate hole index (pHI) and according to WHO guidelines.
For all respondents, exposure to BCC messages was strongly correlated with increased positive attitude towards care and repair, and increases in attitude were positively correlated with observed net repairs, and with the proportion of nets in serviceable condition. In a multivariate regression model, positive care and repair attitude (OR 6.17 p = 0.001) and level of exposure (1 source: OR 4.00 p = 0.000; 3 sources: OR 9.34 p = 0.000) remained the most significant predictors of net condition, controlling for background and environmental factors. Nets that were tied up had 2.70 higher odds of being in serviceable condition (p = 0.001), while repairs made to nets were not sufficient to improve their pHI category. Estimated median net lifespan was approximately one full year longer for nets in households with a positive compared to a negative attitude.
Exposure to multiple channels of a comprehensive BCC intervention was associated with improved attitude scores, and with improved net condition at endline. It is possible for BCC interventions to change both attitudes and behaviours, and to have an important effect on overall median net lifespan. Care and repair messages are easily incorporated into existing malaria BCC platforms, and will help contribute to improved net condition, providing, in principle, more protection from malaria.
Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells ...(MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1). We serially evaluate several facets of the recovery process, including
-integrin expression (a marker of angiogenesis), blood perfusion, and muscle function. We also perform microarray transcriptomics experiments to characterize the gene expression states of the MSC-treated is- chemic tissues, and compare the results with those of non-ischemic tissues, as well as ischemic tissues from a saline-treated control group. The results show a multifaceted impact of mMSCs on hindlimb ischemia. We determined that the angiogenic activity one week after mMSC treatment was enhanced by approximately 80% relative to the saline group, which resulted in relative increases in blood perfusion and muscle strength of approximately 42% and 1.7-fold, respectively. At the transcriptomics level, we found that several classes of genes were affected by mMSC treatment. The mMSCs appeared to enhance both pro-angiogenic and metabolic genes, while suppressing anti-angiogenic genes and certain genes involved in the inflammatory response. All told, mMSC treatment appears to exert far-reaching effects on the microenvironment of ischemic tissue, enabling faster and more complete recovery from vascular occlusion.
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