13 research outputs found
Preliminary seroprevalence study of neurotropic virus antibodies in Nodding syndrome
No full textNodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition
Early-Onset, Conjugal, Twin-Discordant, and Clusters of Sporadic ALS: Pathway to Discovery of Etiology via Lifetime Exposome Research
No full textInternational audienceThe identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease
Explaining agricultural and agrarian policies in developing countries
No full textPolitical outcomes - such as agricultural taxation, subsidization, and the provision of public goods - result from political bargaining among interest groups. Such bargaining is likely to be efficiency-enhancing and growth-enhancing when equally powerful interest groups - aware of the economywide budget constraint and know the economic implications of different policy options - participate, and when impartial institutions are available to enforce decisions. The greater the deviation from these conditions, the greater the potential for efficiency-reducing outcomes, the costs of which will generally fall disproportionately on politically underrepresented or powerless groups. Material conditions of agriculture production - such as spatial dispersion, seasonal work cycles, covariance of risk, and the associated market imperfections - exacerbate the difficulties faced by small producers to engage in collective action. So, despite being generally the economically most efficient form of production, family farmers'ability to counteract the political influence of rural elites and urban dwellers is extremely limited. Lack of independent institutions and clearly defined property rights - and the presence of organizational residues - not only reduce peasants'bargaining power but may also make it more profitable for powerful groups to prefer rent seeking to productive activities. How can these undesirable outcomes be avoided, and how can sustainable policy changes be initiated? Experience indicates that fiscal crises of the state, often triggered or aggravated by an external shock, can cause lasting changes of policies and institutions. By forcing the state to devolve some of its power in exchange for financial assistance to meet its immediate needs, such a crisis can give rise to the emergence of independent legal, political, and economic institutions that are maintained even once the crisis has subsided, External actors that provide resources in terms of crisis and at the same time enhance the scope for politically least vocal parts of civil society to participate in political discourse can have a significant impact on changing policy. The paper discusses in detail the implications for research as well as for policy advice.Labor Policies,Economic Theory&Research,Agricultural Knowledge&Information Systems,Banks&Banking Reform,Environmental Economics&Policies,Environmental Economics&Policies,Economic Theory&Research,Banks&Banking Reform,Agricultural Knowledge&Information Systems,Health Economics&Finance
The Nodding syndrome cerebrospinal fluid proteome: a lens into neurodevelopmental failure consistent with environmentally triggered MECP2 dysregulation?
No full textIntroductionNodding Syndrome (NS) is a childhood-onset epileptic encephalopathy of unknown etiology, occurring in clustered outbreaks across East Africa. Despite extensive investigation, its molecular underpinnings remain unresolved.MethodsWe performed an 18-plex tandem mass tag (TMT)-based quantitative proteomic analysis of immunodepleted cerebrospinal fluid (CSF) from Ugandan NS patients (n = 9) and age-comparable Ugandan Controls (n = 9). Differential protein abundance and pathway-level enrichment analyses were conducted to identify dysregulated molecular networks.ResultsA total of 2,195 CSF proteins were quantified, of which 544 showed statistically significant differential abundance. Dysregulated pathways spanned immune signaling, proteostasis, synaptic function, metabolism, transcriptional regulation, neurovascular integrity, and tau-associated processes. Notably, the NS CSF proteomic profile showed substantial pathway-level convergence with that reported in MECP2 duplication syndrome (MDS), an X-linked neurodevelopmental disorder marked by MECP2 overexpression and systemic immune-metabolic dysfunction. Clinically, NS shares features with both MDS and its mechanistic converse, Rett syndrome, characterized by MECP2 loss-of-function.DiscussionThese convergent molecular and clinical signatures suggest that NS may involve aberrant regulation of MECP2-associated networks. We propose a provisional model in which NS represents an environmentally induced functional phenocopy of MECP2 network dysregulation, shaped by early-life immune and epigenetic perturbations and amplified by postnatal environmental stressors. Although direct epigenetic data and detailed exposure histories are currently limited, this integrative framework provides a testable model linking proteomic alterations and clinical observations to neurodevelopmental and immune-metabolic mechanisms, offering tractable directions for future mechanistic and therapeutic inquiry
Survey data collected per week and per village across the 12-week study period.
No full textCoding: Red—Incomplete number of households (n = 30) surveyed that week. When nNumber—Outliers or values not included in the average ± SD due to incomplete number of households surveyed or household replacement; (*)—Households replaced from one week to another due to relocation, poor road access, or death. (DOCX)</p
Pie charts, one for each village of study, displaying different NS health-related data across the 12-week study period.
No full textColor coding: Red- Proportion of children with NS; Black- Proportion of children with nodding spells reported for the first time; Yellow- Proportion of children with NS who were injured; Green- Proportion of children with NS who died; Blue- Proportion of children with NS who did not have anti-seizure medication. For comparison purposes, the number of children with NS monitored per village was normalized to 100%. Percentages above 100% are indicative of repeated outcomes. The pie chart corresponding to Ludok and Olam villages (bottom right) should be taken only for reader orientation because values summarize data collected for only 4 weeks (S1 Tables).</p
Districts, sub-counties, parishes and villages participating in the mHealth-based community surveillance study.
No full textDistricts, sub-counties, parishes and villages participating in the mHealth-based community surveillance study.</p
Temporal monitoring of NS health data in Paikat Akidi village, Angole parish, Awere sub-county, Pader district.
No full textA) Real-time electronic map for weeks 1, 6, and 12 of data collection. Color coding: Red- Households with at least 1 child with NS; Green- Households with at least 1 child with NS who did not have anti-seizure medication (A); was injured (B); or died (C) that particular week.</p
Data collected in Paikat Akidi village (Angole parish, Awere sub-county, Pader district) throughout the 12-week study period.
No full textData collected in Paikat Akidi village (Angole parish, Awere sub-county, Pader district) throughout the 12-week study period.</p
Screenshot of the <i>Magpi</i> web-interface.
No full textThe image shows a) the user name associated with the mHealth reporter sending the survey record, b) the survey record start and end times, c) the time the record was submitted/uploaded to the Magpi server and d) the GPS stamp.</p
