Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria: A Randomized Clinical Trial.

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae. Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher. Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023. Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher. Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance. Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07). Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia. Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Sudden Vision Loss.

A 37-year-old woman was referred for evaluation of a retinal detachment in her left eye. Posterior examination results demonstrated a retinal detachment in the posterior pole with shifting fluid and no identifiable retinal break, and there was a thickened choroid with a hyporeflective band on ultrasound biomicroscopy. What would you do next?

Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

BACKGROUND AND OBJECTIVE: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR). PATIENTS AND METHODS: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients. Analysis of variance was used in subgroup analysis, receiver operating characteristic (ROC) curves were created to validate reliability of the model, and logistic regression was used to model foci and vascular abnormalities as predictors for moderate or worse disease. RESULTS: A statistically significant difference in mean number of hyporeflective foci was found between no DR and moderate non-proliferative DR (NPDR; P < 0.0001), no DR and severe NPDR (P < 0.001), no DR and proliferative DR (PDR; P < 0.0001), mild and moderate NPDR (P = 0.008), mild and severe NPDR (P < 0.001), and mild NPDR and PDR (P < 0.001). The area under the ROC curve was 0.849 (CI: 0.792 to 0.905). The threshold for detection of moderate NPDR or worse was 4.75 foci, with a sensitivity of 79.0% and a false positive rate of 20.0%. Multivariate logistic regression model incorporating hyporeflective foci with vascular abnormalities (odds ratio [OR] = 1.592, 95% CI: 1.381 to 1.835; P < 0.001) was able to accurately predict moderate disease or worse, just moderate disease (OR = 1.045, 95% CI: 1.003 to 1.089; P = 0.035), severe disease (OR = 1.050, 95% CI: 1.006 to 1.096; P = 0.027), and proliferative disease (OR = 1.050, 95% CI: 1.008 to 1.095; P = 0.018). CONCLUSIONS: NIR imaging may be an adjunct tool in screening for DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:318-325.].

Plant histone variants at the nexus of chromatin readouts, stress and development.

Histones are crucial proteins that are involved in packaging the DNA as condensed chromatin inside the eukaryotic cell nucleus. Rather than being static packaging units, these molecules undergo drastic variations spatially and temporally to facilitate accessibility of DNA to replication, transcription as well as wide range of gene regulatory machineries. In addition, incorporation of paralogous variants of canonical histones in the chromatin is ascribed to specific functions. Given the peculiar requirement of plants to rapidly modulate gene expression levels on account of their sessile nature, histones and their variants serve as additional layers of gene regulation. This review summarizes the mechanisms and implications of distribution, modifications and differential incorporation of histones and their variants across plant genomes, and outlines emerging themes.

Protocol for a Magnetic Resonance Imaging (MRI) Study of Participants in the Fever Randomized Controlled Trial: Does fever control prevent brain injury in malaria?

Background: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. Methods: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. Discussion: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Screening for developmental delay in urban Rwandan children: a cross sectional study.

BACKGROUND: Systematic or targeted screening for developmental delay (DD) is critical to the early identification of developmental disabilities. With limited available information for urban Rwandan children, this study aimed to determine the prevalence of DD and associated risk factors in infants aged 9 to 16 months living in the urban Rwandan city of Kigali. METHODS: A cross-sectional study was conducted in Rwanda from August to November 2019. A convenience sample of 376 Rwandan parents/caregivers and their children attending urban health centers for their routine immunization visits at 9 and 15 months of age was studied. Parents/caregivers completed the official Kinyarwandan version of the Ages and Stages Questionnaire (ASQ-3) and established cutoffs were used to identify DD. Frequency and percentages were used to summarise the data. Logistic regression analysis was used to identify factors associated with DD. RESULTS: Of the 358 children screened using the ASQ-3, the overall prevalence of DD was 24.6%, with a 27.2% prevalence among 9-10-month old children and 22.4% prevalence among 15-16-month old children. Delays in the combined group among the domains of gross motor, communication, fine motor, personal social, and problem solving were 12.8%, 2.5%, 8.4%, 1.7% and 7.5%, respectively. Gestational age at delivery and district of origin were most highly associated with DD, with preterm children at significantly higher risk of having DD compared to term children (Adjusted Odd Ratio AOR = 8.3; 95% CI = 2.5-27.4) and children from Nyarugenge District at high risk of DD compared to children from Gasabo district (AOR = 2.15; 95% CI = 1.2-3.9). CONCLUSIONS: The prevalence of ASQ-detectable DD among urban Rwandan children between 9 and 16 months of age was 24.6%, with a high correlation to a history of prematurity and district of origin. This study demonstrates the need for thoughtful health planning regarding integrated developmental surveillance for children, particularly those at high risk, to allow for earlier identification and intervention in the urban area of Kigali, Rwanda.

Implications of solid waste dumps on the microplastic abundance in groundwater in Kollam, India.

Water pollution caused by microplastics has garnered increasing attention in recent years due to its potential ecological and human health risks. However, there are very limited studies and a general lack of consensus regarding the presence and negative impacts of microplastics in groundwater. Due to their small size, microplastics can easily be transported at surface as well as subsurface levels, potentially reaching the groundwater table and contaminating the groundwater system This contamination is expected to occur more rapidly in landfill areas and other locations where plastic waste is dumped. In this study, we examined well water samples collected from areas near various dumping sites to assess the abundance and characteristics of microplastics. An average of 12 items/L of microplastics were found in groundwater wells near eight dumping sites in Kollam Corporation. The predominant shape of microplastics in the groundwater samples was fibres, followed by flakes, with black being the predominant colour. The areal extent of solid waste dumping was observed to have an influence on the abundance of microplastics. Additionally, the pH of groundwater near heavy dumping sites was found to be in the acidic range, indicating the intrusion of leachate from dumps into groundwater. The study revealed that the leachate from solid waste dumps is the primary source of microplastics in groundwater. Furthermore, a risk assessment of the microplastic pollution was carried out using an index namely Microplastic Pollution Index and the areas of high risks were identified. The locations having heavy solid waste dumping and those near coastal areas were observed to be at high risk, thereby indicating that both the leachate from dumps and sea water intrusion can cause higher microplastic pollution risk in the groundwater system. The findings of this study are expected to support managers in formulating and implementing effective solid waste management plans to mitigate microplastic pollution in the groundwater system.

Evaluation of Microleakage of Stainless Steel Crowns and Pedo Jacket Crowns after Cementation With Different Luting Cements.

Aim: The present research was conducted to assess the microleakage of stainless steel crowns along with pedo jacket crowns following cementation with different luting cements. Materials and Methods: A total of 60 deciduous teeth subjected to extraction were employed in this in vitro research. These 60 specimens were randomly divided into two groups: Group I: Stainless steel crowns and Group II: Pedo Jacket crowns. Both crowns were subjected to cementation using self-cure resin-modified glass ionomer (RMGI) cement as well as by means of self-adhesive universal resin cement (RelyX luting cement). The specimens were subjected to storage in distilled water at 37°C for 24 h and were subjected to 500 thermal cycles between 5°C and 55°C using a dwell span of 30 s. Individual surfaces were assessed for the amount of dye infiltration at the boundaries by the side of the tooth-cement border beneath a stereomicroscope under 50× magnifying power. At the mesial and distal surfaces, the amount of microleakage was measured in micrometers (µm), and the mean value was computed for each sample. Results: Stainless steel crowns subject to cementation with RelyX luting cement exhibited the lowest microleakage (0.88 ± 0.78) versus self-cure RMGI cement (0.94 ± 0.78). There was no statistically significant difference found between the groups. Pedo Jacket crowns subject to cementation with RelyX luting cement exhibited the lowest microleakage (0.96. ± 0.32) while self-cure RMGI cement (1.83 ± 0.16) depicted the maximum microleakage. There was an extremely statistically noteworthy dissimilarity noted among the groups. Conclusion: The current research concluded that Pedo Jacket crowns subjected to cementation with RelyX luting cement can be regarded as an esthetically pleasing restorative alternative for numerous young patients. Applying RelyX luting cement to Pedo Jacket crowns provides a strong bolstering by composite materials that ensures the success of the therapy provided.

Follow-up Rates After Teleretinal Screening for Diabetic Retinopathy: Assessing Patient Barriers to Care.

Purpose: To study patient follow-up after they engage in a teleretinal screening program and to understand potential barriers to care. Methods: This was a retrospective analysis and a prospective study of telephone-based patient interviews of outpatients screened for diabetic retinopathy (DR) through a teleretinal referral system. Results: Of 2761 patients screened through a teleretinal referral program, 123 (4.5%) had moderate nonproliferative DR (NPDR), 83 (3.0%) had severe NPDR, and 31 (1.1%) had proliferative DR. Of the 114 patients with severe NPDR or worse, 67 (58.8%) saw an ophthalmologist within 3 months of referral. Eighty percent of interviewed patients reported they were not aware of the need for follow-up eye appointments. Conclusions: Of patients with severe retinopathy or worse, 58.8% presented for in-person evaluation and treatment within 3 months of screening. Although this result was negatively affected by factors related to the COVID-19 pandemic, key elements of patient education and improved referral strategies to facilitate in-person treatment are essential to improving follow-up after patients engage in telescreening.

Total Synthesis of Trisaccharide Repeating Unit of Staphylococcus aureus Strain M.

An efficient total synthesis of a conjugation-ready trisaccharide repeating unit of Staphylococcus aureus strain M is reported here. The main challenges involved in this synthesis are the procurement of rare sugars (d-FucNAc and d-GalNAcA) and installation of consecutive 1,2-cis-glycosidic linkages between them. Stereoselective 1,2-cis glycosylation with the linker acceptor was achieved with easily accessible benzylidene protected d-galactosamine thioglycoside by employing a DMF modulated preactivation glycosylation method. The consecutive 1,2-cis linkages were installed with the help of solvent participation. The carboxylic acid functionality was introduced via postglycosylation oxidation on the disaccharide moiety. The total synthesis of trisaccharide repeating unit was accomplished with the longest linear sequence of 24 steps in 4.5% overall yield.

Consensus Competencies for Postgraduate Fellowship Training in Global Neurology.

BACKGROUND AND OBJECTIVES: Use a modified Delphi approach to develop competencies for neurologists completing ≥1 year of advanced global neurology training. METHODS: An expert panel of 19 United States-based neurologists involved in global health was recruited from the American Academy of Neurology Global Health Section and the American Neurological Association International Outreach Committee. An extensive list of global health competencies was generated from review of global health curricula and adapted for global neurology training. Using a modified Delphi method, United States-based neurologists participated in 3 rounds of voting on a survey with potential competencies rated on a 4-point Likert scale. A final group discussion was held to reach consensus. Proposed competencies were then subjected to a formal review from a group of 7 neurologists from low- and middle-income countries (LMICs) with experience working with neurology trainees from high-income countries (HICs) who commented on potential gaps, feasibility, and local implementation challenges of the proposed competencies. This feedback was used to modify and finalize competencies. RESULTS: Three rounds of surveys, a conference call with United States-based experts, and a semistructured questionnaire and focus group discussion with LMIC experts were used to discuss and reach consensus on the final competencies. This resulted in a competency framework consisting of 47 competencies across 8 domains: (1) cultural context, social determinants of health and access to care; (2) clinical and teaching skills and neurologic medical knowledge; (3) team-based practice; (4) developing global neurology partnerships; (5) ethics; (6) approach to clinical care; (7) community neurologic health; (8) health care systems and multinational health care organizations. DISCUSSION: These proposed competencies can serve as a foundation on which future global neurology training programs can be built and trainees evaluated. It may also serve as a model for global health training programs in other medical specialties as well as a framework to expand the number of neurologists from HICs trained in global neurology.

Co-existence of Extended Spectrum ß-Lactamase and carbapenemase-producing genes from Diarrheagenic Enteric pathogens isolated in a tertiary care hospital.

Multiple drug resistance (MDR) among bacterial pathogens is a growing concern that clinicians are facing worldwide. Diarrhea among infants is frequent and is caused by various bacterial and viral infectious agents. Two hundred and twelve stool specimens were collected from pediatric patients from a rural quaternary hospital in Barshi, Sholapur, India, between March and December 2017. Total 180 specimens were positive for various bacterial pathogens, while the remaining 32 diarrhea cases may have been caused by a viral or uncultured bacterial pathogen. Identification of the bacterium and its antibiotic susceptibility were primarily carried out with VITEK-2. Distribution of diarrhea-causing bacteria among the 180 samples was as follows: 61.11% (110) Escherichia coli, 30.55% (55) Klebsiella pneumoniae, 4.44% (8) Proteus mirabilis, 2.22% (4) Shigella spp. 1.11% (2) Morganella morganii and 0.55% (1) each for Enterobacter cloacae and Citrobacter koseri. There was a co-existence of multiple genetic traits conferring extreme drug resistance (XDR) status to 19 isolates, 17 of which were determined to be E. coli and one each of E. cloacae and C. koseri. Antibiotype determination using VITEK-2 and polymerase chain reaction (PCR) amplification of the genetic traits indicated the co-existence of blaTEM and blaCTX-M15 isolates in all 19 isolates, with the exception of E. cloacae. Results showed that 10 out of 19 strains expressed the AmpC cephalosporinase blaCMY-2 gene, whereas metallo-carbapenemase was expressed in four isolates. Distribution of blaNDM-11 and acquired penicillinase blaSHV-1 resistance among 180 clinical isolates is discussed in the light of ESBL traits. This is the first report from the rural part of Maharashtra India showing that as many as 10.55% of the pathogenic strains were XDR, a step ahead of MDR.

Educational guidelines for diversity and inclusion: addressing racism and eliminating biases in medical education.

Racism and bias contribute to healthcare disparities at a patient and population health level and also contribute to the stagnation or even regression of progress toward equitable representation in the workforce and in healthcare leadership. Medical education and healthcare systems have expended tremendous efforts over the past several years to address these inequities. However, systemic racism continues to impact health outcomes and the future physician workforce. The Association of Professors of Gynecology and Obstetrics called for action to achieve a future free from racism in obstetrics and gynecology education and healthcare. As a result of this call to action, the Diversity, Equity, and Inclusion Guidelines Task Force was created. The mission of the Task Force was to support educators in their efforts to identify and create educational materials that augment antiracist educational goals and prepare, recruit, and retain a talented and diverse workforce. In this Special Report, the authors share these guidelines that describe best practices and set new standards to increase diversity, foster inclusivity, address systemic racism, and eliminate bias in obstetrics and gynecology educational products, materials, and environments.

Interlacing the relevance of caspase activation in the onset and progression of Alzheimer's disease.

Caspases, a family of cysteine proteases is a renowned regulator of apoptosis. Members of this family are responsible for the proteolytic dismantling of numerous cellular structures. Apart from apoptosis, caspases remarkably contribute to a diverse range of molecular processes. Being the imperative members of several cellular cascades their abnormal activation/deactivation has severe implications and also leads to various diseased conditions. Similar aberrant activation of caspases is one of the several causes of neuropathologies associated with Alzheimer's disease (AD), a form of dementia severely affecting neuropsychiatric and cognitive functions. Emerging studies are providing deeper insights into the mechanisms of caspase action in the progression of AD. Current article is an attempt to review these studies and present the action mechanisms of different mammalian caspases in the advancement of AD associated neuropathologies.

Spotlight on Faricimab in the Treatment of Wet Age-Related Macular Degeneration: Design, Development and Place in Therapy.

The advent of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of retinal neovascular diseases including neovascular age-related macular degeneration (nAMD), a leading cause of irreversible blindness. Multiple agents and methods for drug delivery are emerging to increase the duration of treatment effect and treatment interval, reducing the overall treatment burden on patients and clinicians. The newest agent on the market is faricimab. This medication targets two distinct pathways in retinal angiogenesis, VEGF-A and Ang-2, to create a more durable effect. Phase 3 trials for this drug compared treatment intervals up to 16 weeks against aflibercept dosed at 8-week intervals for both nAMD and diabetic macular edema (DME). While the drug shows similar functional and anatomic outcomes with a low adverse effect profile and trial data demonstrating increased treatment duration, its exact place in the VEGF marketplace is yet to be determined. In this article, we discuss the mechanism of action, pivotal clinical trials leading to approval, and the anticipated role for faricimab in the treatment of retinal neovascular disease.

Differential detection of IgM and IgG antibodies to chimeric antigens in bovine tuberculosis.

Recent studies have suggested the potential of innovative serologic tests for accurate and rapid detection of bovine tuberculosis (bTB). Dual Path Platform (DPP) technology has been used to develop rapid animal-side antibody tests for Mycobacterium bovis infection in a range of livestock and wildlife host species. The present study evaluated diagnostic performance of DPP BovidTB IgM/IgG assay designed for differential detection of bovine IgM and IgG antibodies against two chimeric antigens, DID38 and TBf2, respectively, using 662 well-characterized serum samples from M. bovis-infected and bTB-free cattle collected in the United States, Great Britain, France, and South Africa. Test sensitivity and specificity ranged from 71% to 100% and from 95% to 100%, respectively, depending on the country, with overall accuracy of 83%. No significant risk of cross-reactivity with serum samples from cattle infected with most relevant species of mycobacteria other than M. bovis was found. The DPP BovidTB IgM/IgG assay may be suitable for use in multi-test algorithms to improve current strategies for bTB surveillance.

Anemia control program in india needs to be more comprehensive.

Iron-deficiency anemia has continued to remain high in India. It is possibly due to relying on only iron-folic acid (IFA) supplementation through Anemia Control Program (ACP) that is National Iron Plus Initiative (NIPI). Based on the WHO's recommendations, we studied different interventions that can help to increase the effectiveness of NIPI such as Vitamin C supplementation with IFA, low-dose iron (LDI) with intensified health education (IHE), LDI with Vitamin C, and iron-rich food items to increase hemoglobin (Hb%) among adolescent girls through public-private partnership named Rashtriya Kishor Swasthya Karyakram. Increments in Hb after 12 weeks of interventions were compared with that of control groups one with NIPI and the other without any intervention. Highest increment in Hb% was observed in IFA under NIPI plus Vitamin C group, followed by LDI plus IHE group which was comparable to Hb increment in only the NIPI group. It emphasizes the need of making existing NIPI more stringent and comprehensive by integrating effective measures based on up-to-date scientific knowledge.

Two cases of unilateral cone-rod dysfunction presenting in adult females.

PURPOSE: To describe cases of unilateral cone-rod dysfunction presenting in two middle-aged females. METHODS: This case series highlights two middle-aged female patients with progressive visual decline in one eye. Fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), multi-focal electroretinogram (mfERG), full-field electroretinogram(ffERG), and genetic testing were obtained. RESULTS: In the first patient, mfERG showed an extinguished response and ffERG demonstrated markedly reduced a-wave and b-wave amplitudes (more pronounced under photopic conditions) in the right eye. SD-OCT showed attenuation of the ellipsoid zone of the right eye. Similar findings were appreciated in the second patient. Genetic testing in the first patient identified three heterozygous variants in PRPH2, RCBTB1, and USH2A. The second patient was found to have heterozygous variants in BBS1 and ABCA4. CONCLUSION: These two cases add to the literature of case reports of unilateral cone-rod and rod-cone dystrophies. However, the underlying etiology of the unilateral pattern of cone-rod dysfunction and the significance of the heterozygous mutations found in both cases remains uncertain.

Identifying biomarkers for epilepsy after cerebral malaria in Zambian children: rationale and design of a prospective observational study.

INTRODUCTION: Malaria affecting the central nervous system (CM) is a major contributor to paediatric epilepsy in resource-poor settings, with 10%-16% of survivors developing epilepsy within 2 years of infection. Despite high risk for post-malaria epilepsy (PME), biomarkers indicating which CM survivors will develop epilepsy are absent. Such biomarkers are essential to identify those at highest risk who might benefit most from close surveillance and/or preventive treatments. Electroencephalography (EEG) contains signals (specifically gamma frequency activity), which are correlated with higher risk of PME and provide a biomarker for the development of epilepsy. We propose to study the sensitivity of quantitative and qualitative EEG metrics in predicting PME, and the potential increased sensitivity of this measure with additional clinical metrics. Our goal is to develop a predictive PME index composed of EEG and clinical history metrics that are highly feasible to obtain in low-resourced regions. METHODS AND ANALYSES: This prospective observational study being conducted in Eastern Zambia will recruit 250 children aged 6 months to 11 years presenting with acute CM and follow them for two years. Children with pre-existing epilepsy diagnoses will be excluded. Outcome measures will include qualitative and quantitative analysis of routine EEG recordings, as well as clinical metrics in the acute and subacute period, including histidine-rich protein 2 levels of parasite burden, depth and length of coma, presence and severity of acute seizures, presence of hypoglycaemia, maximum temperature and 1-month post-CM neurodevelopmental assessment scores. We will test the performance of these EEG and clinical metrics in predicting development of epilepsy through multivariate logistic regression analyses. ETHICS AND DISSEMINATION: This study has been approved by the Boston Children's Hospital Institutional Review Board, University of Zambia Biomedical Research Ethics Committee, and National Health Research Authority of Zambia. Results will be disseminated locally in Zambia followed by publication in international, open access, peer-reviewed journals when feasible.