2,476 research outputs found

    Caregiver characteristics.

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    BackgroundCurrent formulations of pediatric antiretroviral therapy (ART) for children with HIV present significant barriers to adherence, leading to drug resistance, ART ineffectiveness, and preventable child morbidity and mortality. Understanding these challenges and how they contribute to suboptimal adherence is an important step in improving outcomes. This qualitative study describes how regimen-related challenges create barriers to adherence and impact families.MethodsWe conducted key informant interviews (KIIs) with 30 healthcare providers and 9 focus group discussions (FGDs) with a total of 72 caregivers, across three public hospitals in Siaya and Mombasa Kenya. The KIIs and FGDs were audio recorded, translated, and transcribed verbatim. The transcripts were hand coded based on emergent and a-priori themes.ResultsCaregivers discussed major regimen-related challenges to adherence included poor palatability of current formulations, complex preparation, and administration (including measuring, crushing, dissolving, mixing), complex drug storage, and frequent refill appointments and how these regimen-related challenges contributed to individual and intrapersonal barriers to adherence. Caregivers discussed how poor taste led to child anxiety, refusal of medications, and the need for caregivers to use bribes or threats during administration. Complex preparation led to concerns and challenges about maintaining privacy and confidentiality, especially during times of travel. Providers corroborated this patient experience and described how these challenges with administration led to poor infant outcomes, including high viral load and preventable morbidity. Providers discussed how the frequency of refills could range from every 2 weeks to every 3 months, depending on the patient. Caregivers discussed how these refill frequencies interrupted work and school schedules, risked unwanted disclosure to peers, required use of financial resources for travel, and ultimately were a challenge to adherence.ConclusionThese findings highlight the need for improved formulations for pediatric ART to ease the daily burden on caregivers and children to increase adherence, improve child health, and overall quality of life of families.</div

    Provider characteristics.

    No full text
    BackgroundCurrent formulations of pediatric antiretroviral therapy (ART) for children with HIV present significant barriers to adherence, leading to drug resistance, ART ineffectiveness, and preventable child morbidity and mortality. Understanding these challenges and how they contribute to suboptimal adherence is an important step in improving outcomes. This qualitative study describes how regimen-related challenges create barriers to adherence and impact families.MethodsWe conducted key informant interviews (KIIs) with 30 healthcare providers and 9 focus group discussions (FGDs) with a total of 72 caregivers, across three public hospitals in Siaya and Mombasa Kenya. The KIIs and FGDs were audio recorded, translated, and transcribed verbatim. The transcripts were hand coded based on emergent and a-priori themes.ResultsCaregivers discussed major regimen-related challenges to adherence included poor palatability of current formulations, complex preparation, and administration (including measuring, crushing, dissolving, mixing), complex drug storage, and frequent refill appointments and how these regimen-related challenges contributed to individual and intrapersonal barriers to adherence. Caregivers discussed how poor taste led to child anxiety, refusal of medications, and the need for caregivers to use bribes or threats during administration. Complex preparation led to concerns and challenges about maintaining privacy and confidentiality, especially during times of travel. Providers corroborated this patient experience and described how these challenges with administration led to poor infant outcomes, including high viral load and preventable morbidity. Providers discussed how the frequency of refills could range from every 2 weeks to every 3 months, depending on the patient. Caregivers discussed how these refill frequencies interrupted work and school schedules, risked unwanted disclosure to peers, required use of financial resources for travel, and ultimately were a challenge to adherence.ConclusionThese findings highlight the need for improved formulations for pediatric ART to ease the daily burden on caregivers and children to increase adherence, improve child health, and overall quality of life of families.</div

    FGD characteristics.

    No full text
    BackgroundCurrent formulations of pediatric antiretroviral therapy (ART) for children with HIV present significant barriers to adherence, leading to drug resistance, ART ineffectiveness, and preventable child morbidity and mortality. Understanding these challenges and how they contribute to suboptimal adherence is an important step in improving outcomes. This qualitative study describes how regimen-related challenges create barriers to adherence and impact families.MethodsWe conducted key informant interviews (KIIs) with 30 healthcare providers and 9 focus group discussions (FGDs) with a total of 72 caregivers, across three public hospitals in Siaya and Mombasa Kenya. The KIIs and FGDs were audio recorded, translated, and transcribed verbatim. The transcripts were hand coded based on emergent and a-priori themes.ResultsCaregivers discussed major regimen-related challenges to adherence included poor palatability of current formulations, complex preparation, and administration (including measuring, crushing, dissolving, mixing), complex drug storage, and frequent refill appointments and how these regimen-related challenges contributed to individual and intrapersonal barriers to adherence. Caregivers discussed how poor taste led to child anxiety, refusal of medications, and the need for caregivers to use bribes or threats during administration. Complex preparation led to concerns and challenges about maintaining privacy and confidentiality, especially during times of travel. Providers corroborated this patient experience and described how these challenges with administration led to poor infant outcomes, including high viral load and preventable morbidity. Providers discussed how the frequency of refills could range from every 2 weeks to every 3 months, depending on the patient. Caregivers discussed how these refill frequencies interrupted work and school schedules, risked unwanted disclosure to peers, required use of financial resources for travel, and ultimately were a challenge to adherence.ConclusionThese findings highlight the need for improved formulations for pediatric ART to ease the daily burden on caregivers and children to increase adherence, improve child health, and overall quality of life of families.</div

    Assessment of groundwater potential zones using remote sensing and GIS-based fuzzy analytical hierarchy process (F-AHP) in Mpwapwa District, Dodoma, Tanzania

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    Groundwater is a very important resource for socio-economic development. The uncertainty of where potential groundwater resources is located often causes some groundwater development projects to fail. It is common for water resources development projects hitting dry wells after heavy investments of resources. In Mpwapwa District, borehole drilling locations are uncertain, determined by trial-and-error techniques based on geophysical survey methods that involve the study of the behaviour of rock and soil types in specific geological locations. To reduce such uncertainty, this study used remote sensing and GIS-based Fuzzy Analytical Hierarchical Process (F-AHP) to simulate groundwater potential zones (GWPZ) in Mpwapwa District, Dodoma region, Tanzania. The F-AHP model was used to reclassify, weight, and rank various thematic maps, including lithology, soil types, drainage density, lineament, magnetic intensity, slope and elevation. The overall GWPZ map was created by combining the seven (7) ranking thematic map layers in a GIS environment. The resulting GWPZ map that was then validated using two methods: overlaying method and area under the curve (AUC) method. The resulting GWPZ map shows that 19%, 31%, 28% and 22% of the area are classified as very good, good, moderate, poor and very poor zones, respectively. The accuracy of the generated map is 72% using the overlaying method and 93% using the AUC method

    Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

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    Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders

    Anti-inflammatory and antioxidant activities of ethylacetate fraction of Sida linifolia L. (Malvaceae)

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    Sida linifolia L., a known weed found in West Africa and other parts of the world, is being used in African traditional medicine for many purposes, including the relief of uncomfortable teething, and the prevention of malaria. This study aimed to fractionate the crude extract of S. linifolia and determine the anti-inflammatory, and antioxidant properties of the most potent fraction. In the examination of anti-inflammatory compounds, in vitro tests for platelet aggregation, albumin denaturation, protease, and phospholipase A2 were utilized. To assess the in vivo anti-inflammatory effects, rat paw edema was induced with carrageenan and egg albumin. The total antioxidant capacity (TAC), 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing power (FRAP), and nitric oxide (NO) assays were used in the in vitro antioxidant assessment. The result of the phytochemical screening revealed that there were varying concentrations of terpenoids, saponins, steroids, alkaloids, flavonoids, tannins, and other phenols. The ethylacetate leaf fraction of S. linifolia EALFSL displayed robust, concentration-dependent anti-inflammatory effects by significantly inhibiting hypotonicity-and heat-induced hemolysis, platelet aggregation, protein denaturation, protease activity, and phospholipase A2 activity, which were comparable to those of the reference drugs (aspirin/prednisolone). In vivo studies also revealed that EALFSL was able, at different doses, to inhibit the progress of carrageenan-induced rat paw edema and egg albumin models. Though it was less active than the butylated hydroxytoluene BHT (0.30 mg/ml), ascorbic acid (0.32-0.50 mg/ml), and gallic acid (0.47 mg/ml), the EALFSL fraction's IC50 values ranged from 0.93 to 1.20 mg/ml. The results demonstrated that EALFSL has significant concentration-dependent antioxidant activity. These suggest that the ethylacetate leaf fraction of S. linifolia possesses anti-inflammatory and antioxidant effects

    Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: An observational and genomic study

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    Background: Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle. Methods: We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon. Results: We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective (256perdeathaverted),onlydogvaccinationinterruptstransmission.AcombinedOneHealthapproachofroutineannualdogvaccinationtogetherwithfreepost−exposurevaccinesforbitevictims,rapidlyeliminatesrabies,ishighlycost−effective(256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective (1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island. Conclusions: A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere. Funding: Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa’s Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421

    Heterotypic Stressors Unmask Behavioral Influences of PMAT Deficiency in Mice

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    Certain life stressors having enduring physiological and behavioral consequences, in part by eliciting dramatic signaling shifts in monoamine neurotransmitters. High monoamine levels can overwhelm selective transporters like the serotonin transporter. This is when polyspecific transporters like plasma membrane monoamine transporter (PMAT, Slc29a4) are hypothesized to contribute most to monoaminergic signaling regulation. Here, we employed two distinct counterbalanced stressors—fear conditioning and swim stress—in mice to systematically determine how reductions in PMAT function affect heterotypic stressor responsivity. We hypothesized that male heterozygotes would exhibit augmented stressor responses relative to female heterozygotes. Decreased PMAT function enhanced context fear expression, an effect unexpectedly obscured by a sham stress condition. Impaired cued fear extinction retention and enhanced context fear expression in males were conversely unmasked by a sham swim condition. Abrogated corticosterone levels in male heterozygotes that underwent swim stress after context fear conditioning did not map onto any measured behaviors. In sum, male heterozygous mouse fear behaviors proved malleable in response to preceding stressor or sham stress exposure. Combined, these data indicate that reduced male PMAT function elicits a form of stress-responsive plasticity. Future studies should assess how PMAT is differentially affected across sexes and identify downstream consequences of the stress-shifted corticosterone dynamics
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