Report from the child neurology education and training workshop at the International Child Neurology Congress 2024: Expert'saddressing the training gap.

This report summarizes the key findings of a workshop undertaken at the International Child Neurology Congress in 2024 by child neurologists with expertise in training education and invested colleagues. The workshop aimed to explore global issues which have impact on access to child neurology training. The major findings supported a great need for more training programs globally, that consensus is needed for the minimum standards of training, and that training programs can be strengthened via global health partnerships especially with collaborations from regions with more available resources. The group concurred that the phenomena of 'neurophobia' amongst general paediatricians and medical trainees, was a reality, and creates barriers both working with paediatric colleagues, as well as recruiting specialists to the field. Optimal teaching practices for child neurology should include the expansion of learning through global partnerships and virtual educational resources. Measures must be put into place for fledgling training programs, to support colleagues in less resourced settings and to avoid their burn-out. Collegial and collaborative work is essential to support the future of child neurology across the globe, both to reach the current capacity needs but also to meet the necessary growth in the field.

Dengue-Associated Acute Necrotizing Encephalopathy Is an Acute Necrotizing Encephalopathy Variant Rather than a Mimic: Evidence From a Systematic Review.

BACKGROUND: Bilateral hemorrhagic thalamic lesions in dengue encephalitis resemble lesions seen in acute necrotizing encephalopathy (ANE). We investigate whether dengue-associated ANE (DANE) should be considered an ANE variant or a mimic. METHODS: Systematic review of dengue encephalitis literature from PubMed and SCOPUS (inception to December 31, 2022). Diagnostic criteria for ANE, acute encephalitis (AE), acute disseminated encephalomyelitis (ADEM), and infection-triggered encephalopathy syndromes were applied. RESULTS: Data on 162 patients (median age 20 [0.4 to 79] years; 69 [42.3%] female; 72 [44.4%] aged ≤18 years) from 103 articles were analyzed. DANE (62, 38.3%) was the commonest, followed by AE (56, 34.6%) and ADEM (27, 16.7%). The main clinical features were fever (100%), thrombocytopenia (79.0%), headache (57.8%), and seizures (43.7%). Patients with DANE had earlier neurological deterioration (3.5 [1 to 8] vs 5 [1 to 14] days in other encephalitis syndromes, P = 0.0127), seizures (54.2% vs 37.4%, P = 0.0471), higher cerebrospinal fluid (CSF) protein (0.92 [0.18 to 4.8] vs 0.73 [1 to 16] g/L, P = 0.0469), thalamic (100% vs 8.0%) and hemorrhagic brain lesions (73.3% vs 7.5%, P < 0.0001). CSF pleocytosis and positive CSF dengue IgM/viral polymerase chain reaction were reported in 66.7% and 78.6% with DANE. Mortality was 16.1% in DANE, and 40.6% of survivors had disability. High-risk ANE severity scores predicted poor outcomes (positive predictive value 64.3% [95% confidence interval 38.8% to 83.7%]). CONCLUSION: DANE differs from other dengue encephalitis syndromes and is clinicoradiologically indistinguishable from sporadic ANE with sufficient evidence to be considered an ANE variant.

Child Neurology: Acute Necrotizing Encephalopathy of Childhood Associated With Dengue: Good Neurologic Outcome Despite a Fulminant Presentation.

Acute necrotizing encephalopathy of childhood (ANEC) is characterized by a rapidly progressive encephalopathy after a viral febrile illness, with multiple, symmetrical lesions in the brain including the thalami. Acute dengue fever is a known, but rare, trigger for ANEC. The clinical course of ANEC is usually fulminant and is associated with high morbidity and mortality. We describe here a prospective cohort of 5 children who presented with ANEC associated with dengue infection characterized by encephalopathy within the first week of fever, followed by a rapidly deteriorating sensorium requiring intensive care unit admission. Dengue fever was diagnosed based on a positive nonstructural protein 1 antigen test. ANEC was diagnosed based on characteristic MRI brain findings including the "trilaminar sign" in bilateral thalami combined with clinical features of severe encephalopathy, thrombocytopenia, and transaminitis. All the children required prolonged hospital stay (mean duration 30 days), with 4 of 5 children requiring mechanical ventilation (mean duration 21 days). All the children received immunomodulation with IV methylprednisolone either alone or followed by IV immunoglobulin. Although these children were bedridden at discharge (modified Rankin Scale, mRS score 4 or 5), they showed a consistent recovery in follow-up. At 6 months of follow-up, all the children were fully independent in activities of daily living (mRS scores 1-2). These cases highlight good neurologic outcomes in children with ANEC associated with dengue despite a catastrophic presentation and a protracted hospital course. The most common residual neurologic deficits noted were hand tremors and extrapyramidal dysarthria.

Acquired Demyelination Syndrome in Children and Adolescents: 10 Years Experience from a Tertiary Care Centre in North India.

BACKGROUND: The childhood central nervous system (CNS) acquired demyelinating syndromes (ADS) can be monophasic or recurrent, with both having considerable overlap in the first decade of life. OBJECTIVES: The objective of the study was to describe clinical and radiological features, immunological characteristics, response to therapy and difference between monophasic and first episode of recurrent disorders of pediatric-onset CNS ADS. METHODS: Case records of all patients presenting with CNS ADS to the Department of Pediatrics between January 2009 to December 2018 were retrospectively reviewed. Those with complete records and at least 12 months follow up were included for analysis. RESULTS: Overall 95 case records were reviewed (66 monophasic: 20 ADEM and 46 CIS, 29 recurrent: 18 MS, 9 NMOSD, and 2 multiphasic ADEM). The median age of the cohort was 7 years (range: 1-12) and nearly two-thirds (62/95) were males. All acute cases were treated with intravenous pulse followed by tapering oral steroid therapy. All the recurrent entities received azathioprine with rituximab in few. Certain clinical and radiological features of CIS and immune and inflammatory characteristics in CSF were found to be significantly different in monophasic cases compared to first episode of recurrent cases. CONCLUSIONS: The CNS ADS show favourable response to immunotherapy. Azathioprine may be an effective long term immunomodulator, particularly in resource limited settings. Certain clinical, radiological and immunological features may differentiate monophasic illness from first episode of recurrent disorder.

Pregnancy Outcomes and Maternal Periodontal Diseases: The Unexplored Connection.

In the early 20th century, numerous in-vitro studies, animal studies, epidemiological studies, and human trials have attempted to demonstrate the interrelationship between pregnancy outcomes and maternal periodontal disease. This review aims to shed light on the unexplored connections between pregnancy outcomes and maternal periodontal diseases. A literature search was conducted using electronic databases such as PubMed, Scopus, Google Scholar, Web of Science, and Embase. Our research focuses on the role of epigenetics, maternal vitamin D status, stress levels, genetic factors, innate immunity, pattern recognition receptors, and any potential paternal influence, and their possible connections to maternal periodontal disease. Although the precise etiologies and pathogenic mechanisms of the adverse pregnancy outcomes remain obscure, substantial affirmation of the inter-relationship between maternal periodontal diseases and adverse pregnancy outcomes may prove to be of public health relevance as periodontitis can certainly be prevented and treated. Maternal periodontal disease may augment the probability of jeopardizing maternal health causing adverse effects on the pregnancy and neonatal morbidity. Hence, emphasis should be placed on an early diagnosis and management of periodontal diseases. Routine oral health evaluation during prenatal care should be encouraged to combat complications. Ensuing endeavors should be undertaken to help find plausible mechanisms keeping in view the future research domains and new pathways.

Nanomaterial in controlling biofilms and virulence of microbial pathogens.

The escalating threat of antimicrobial resistance (AMR) poses a grave concern to global public health, exacerbated by the alarming shortage of effective antibiotics in the pipeline. Biofilms, intricate populations of bacteria encased in self-produced matrices, pose a significant challenge to treatment, as they enhance resistance to antibiotics and contribute to the persistence of organisms. Amid these challenges, nanotechnology emerges as a promising domain in the fight against biofilms. Nanomaterials, with their unique properties at the nanoscale, offer innovative antibacterial modalities not present in traditional defensive mechanisms. This comprehensive review focuses on the potential of nanotechnology in combating biofilms, focusing on green-synthesized nanoparticles and their associated anti-biofilm potential. The review encompasses various aspects of nanoparticle-mediated biofilm inhibition, including mechanisms of action. The diverse mechanisms of action of green-synthesized nanoparticles offer valuable insights into their potential applications in addressing AMR and improving treatment outcomes, highlighting novel strategies in the ongoing battle against infectious diseases.

Child Neurology: Allgrove Syndrome: An Intriguing Etiology of Motor Neuron Disease in Children

Motor neuron diseases are a rare group of neurodegenerative disorders with considerable phenotypic heterogeneity and a multitude of etiologies in the pediatric population. In this study, we report 2 unrelated adolescents (a boy and a girl) who presented with 4-6 years of progressive difficulty in walking, thinning of limbs, and gradually progressive darkening of the skin. Examination revealed generalized hyperpigmentation of skin and features suggestive of motor neuron involvement such as tongue atrophy, wasting of distal extremities, and brisk deep tendon reflexes. On detailed exploration for systemic involvement, history of dysphagia, inability to produce tears, and Addisonian crises were evident. An etiologic diagnosis of Allgrove syndrome, which is characterized by a triad of achalasia, alacrimia, and adrenal insufficiency was considered. Next-generation sequencing revealed pathogenic variants in the AAAS gene, confirming the diagnosis. Steroid replacement therapy was initiated along with relevant multidisciplinary referrals. The disease stabilized in the boy and a significant improvement was noted in the girl. These cases highlight the value of non-neurologic cues in navigating the etiologic complexities of motor neuron diseases in children and adolescents. It is imperative for neurologists to develop awareness of the diverse neurologic manifestations associated with Allgrove syndrome because they are often the first to be approached. A multidisciplinary team of experts including neurologists, endocrinologists, gastroenterologists, ophthalmologists, and dermatologists is essential for planning comprehensive care for these patients.

Harnessing Nanovaccines for Effective Immunization─A Special Concern on COVID-19: Facts, Fidelity, and Future Prospective.

Nanotechnology has emerged as a transformative pathway in vaccine research and delivery. Nanovaccines, encompassing lipid and nonlipid formulations, exhibit considerable advantages over traditional vaccine techniques, including enhanced antigen stability, heightened immunogenicity, targeted distribution, and the potential for codelivery with adjuvants or immune modulators. This review provides a comprehensive overview of the latest advancements and applications of lipid and non-lipid-based nanovaccines in current vaccination strategies for immunization. The review commences by outlining the fundamental concepts underlying lipid and nonlipid nanovaccine design before delving into the diverse components and production processes employed in their development. Subsequently, a comparative analysis of various nanocarriers is presented, elucidating their distinct physicochemical characteristics and impact on the immune response, along with preclinical and clinical studies. The discussion also highlights how nanotechnology enables the possibility of personalized and combined vaccination techniques, facilitating the creation of tailored nanovaccines to meet the individual patient needs. The ethical aspects concerning the use of nanovaccines, as well as potential safety concerns and public perception, are also addressed. The study underscores the gaps and challenges that must be overcome before adopting nanovaccines in clinical practice. This comprehensive analysis offers vital new insights into lipid and nonlipid nanovaccine status. It emphasizes the significance of continuous research, collaboration among interdisciplinary experts, and regulatory measures to fully unlock the potential of nanotechnology in enhancing immunization and ensuring a healthier, more resilient society.

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Comparative Assessment of Periodontal Status in Subjects with and without Polycystic Ovary Syndrome and its Correlation with Body Mass Index: A Cross-Sectional Study.

New avenues for research have opened, which assess the influence of systemic disease on periodontium and vice versa. To find the correlation between polycystic ovary syndrome (PCOS) and periodontium by assessing clinical parameters [plaque index (PI), probing depth, periodontal disease index (PDI)] and the anthropological parameter [body mass index (BMI)] and to find the correlation between body mass index and periodontal disease index in subjects with and without PCOS. Sixty females comprising 30 with PCOS and 30 without PCOS were selected. Clinical, anthropological, and radiological assessment was done. Double blinding was incorporated. There was a statistically highly significant difference in mean age, mean PI, and mean PDI (P < 0.001) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. A statistically significant difference was found in mean probing depth and mean BMI (P < 0.05) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. No statistically significant correlation was found between mean PDI and mean BMI in PCOS and non-PCOS group subjects using Spearman's rank correlation. Women suffering from PCOS may be at a heightened risk for developing periodontal disease as our study re-establishes this association with respect to some periodontal parameters. With such a result, general practitioners/gynecologists can be encouraged to refer cases of PCOS to periodontists for early detection, prevention of periodontal disease, and maintenance of periodontal health.

Selective Enhancer Dependencies in MYC -Intact and MYC -Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma.

High expression of MYC and its target genes define a subset of germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) associated with poor outcomes. Half of these high-grade cases show chromosomal rearrangements between the MYC locus and heterologous enhancer-bearing loci, while focal deletions of the adjacent non-coding gene PVT1 are enriched in MYC -intact cases. To identify genomic drivers of MYC activation, we used high-throughput CRISPR-interference (CRISPRi) profiling of candidate enhancers in the MYC locus and rearrangement partner loci in GCB-DLBCL cell lines and mantle cell lymphoma (MCL) comparators that lacked common rearrangements between MYC and immunoglobulin (Ig) loci. Rearrangements between MYC and non-Ig loci were associated with unique dependencies on specific enhancer subunits within those partner loci. Notably, fitness dependency on enhancer modules within the BCL6 super-enhancer ( BCL6 -SE) cluster regulated by a transcription factor complex of MEF2B, POU2F2, and POU2AF1 was higher in cell lines bearing a recurrent MYC::BCL6 -SE rearrangement. In contrast, GCB-DLBCL cell lines without MYC rearrangement were highly dependent on a previously uncharacterized 3' enhancer within the MYC locus itself (GCBME-1), that is regulated in part by the same triad of factors. GCBME-1 is evolutionarily conserved and active in normal germinal center B cells in humans and mice, suggesting a key role in normal germinal center B cell biology. Finally, we show that the PVT1 promoter limits MYC activation by either native or heterologous enhancers and demonstrate that this limitation is bypassed by 3' rearrangements that remove PVT1 from its position in cis with the rearranged MYC gene. Key points: CRISPR-interference screens identify a conserved germinal center B cell MYC enhancer that is essential for GCB-DLBCL lacking MYC rearrangements. Functional profiling of MYC partner loci reveals principles of MYC enhancer-hijacking activation by non-immunoglobulin rearrangements.

The Relationship Between Insufficient Vision and Technology Access and Use Among Hospitalized Adults at an Urban Academic Hospital: Observational Study.

BACKGROUND: The role of sufficient vision in self-management is salient with respect to the growing prevalence of eHealth-based interventions for chronic diseases. However, the relationship between insufficient vision and self-management has been understudied. OBJECTIVE: We aimed to assess differences in access to and use of technology among adults with and without insufficient vision at an academic urban hospital. METHODS: This is an observational study of hospitalized adult general medicine patients that is part of a larger quality improvement study called the hospitalist study. The hospitalist study provided demographic and health literacy data (Brief Health Literacy Screen). Our substudy included several measures. Validated surveys assessed technology access and use, and included benchmarked questions from the National Pew Survey to determine access to, willingness to use, and self-described ability to use technology at home, particularly for self-management, and eHealth-specific questions assessing future willingness to access eHealth post discharge. The eHealth Literacy Scale (eHEALS) was used to assess eHealth literacy. Visual acuity was assessed using the Snellen pocket eye chart with low vision defined as visual acuity ≤20/50 in at least one eye. Descriptive statistics, bivariate chi-square analyses, and multivariate logistic regressions (adjusted for age, race, gender, education level, and eHealth literacy) were performed using Stata. RESULTS: A total of 59 participants completed our substudy. The mean age was 54 (SD 16.4) years. Demographic data from the hospitalist study was missing for several participants. Among those who responded, most identified as Black (n=34, 79%) and female (n=26, 57%), and most reported at least some college education (n=30, 67%). Most participants owned technology devices (n=57, 97%) and had previously used the internet (n=52, 86%), with no significant differences between those with insufficient and sufficient vision (n=34 vs n=25). Though there was a 2x effect size for laptop ownership, with those with sufficient vision more likely to own a laptop, those with insufficient vision versus sufficient vision were less likely to report an ability to perform online tasks without assistance, including using a search engine (n=22, 65% vs n=23, 92%; P=.02), opening an attachment (n=17, 50% vs n=22, 88%; P=.002), and using an online video (n=20, 59% vs n=22, 88%; P=.01). In multivariate analysis, the ability to independently open an online attachment did not remain statistically significant (P=.01). CONCLUSIONS: Technology device ownership and internet use rates are high in this population, yet participants with insufficient vision (vs sufficient vision) reported a reduced ability to independently perform online tasks. To ensure the effective use of eHealth technologies by at-risk populations, the relationship between vision and technology use needs to be further studied.

Brain Stimulation and Constraint Induced Movement Therapy in Children With Unilateral Cerebral Palsy: A Randomized Controlled Trial.

BACKGROUND: There is a crucial need to devise optimum rehabilitation programs for children with cerebral palsy (CP). OBJECTIVE: This study aimed to assess the feasibility, safety, and efficacy of combining 6-Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) with modified constraint-induced movement therapy (mCIMT) in improving upper limb function in children with unilateral CP. METHODS: Children aged 5 to 18 years with unilateral CP were randomized (23 in each arm) to receive 10 sessions of mCIMT with real rTMS (intervention arm) or mCIMT with sham rTMS (control arm), on alternate weekdays over 4 weeks. The primary outcome was the difference in mean change in Quality of Upper Extremity Skills Test (QUEST) scores. Secondary outcomes were changes in QUEST domain scores, speed and strength measures, CP quality of life (CP-QOL) scale scores, and safety of rTMS. RESULTS: All 46 children completed the trial except one. At 4 weeks, the mean change in total QUEST scores was significantly higher in the intervention arm as compared to the control arm (11.66 ± 6.97 vs 6.56 ± 4.3, d = 5.1, 95% CI 1.7-8.5, P = .004). Change in "weight bearing" and "protective extension" domain score was significantly higher for children in the intervention arm. These improvements were sustained at 12 weeks (P = .028). CP-QOL scores improved at 12 weeks. No serious adverse events were seen. CONCLUSION: A 6-Hz primed rTMS combined with mCIMT is safe, feasible, and superior to mCIMT alone in improving the upper limb function of children with unilateral CP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03792789.

Primary Hemophagocytic Lymphohistiocytosis With Prolonged Primary Neurologic Presentation.

Primary hemophagocytic lympho-histiocytosis (HLH) is a hyperinflammatory syndrome with devastating consequences. Multisystem involvement is a hallmark of HLH; however, HLH may rarely present with signs and symptoms isolated to the central nervous system (CNS). Within the brain, HLH can mimic demyelination, chronic infection, or vasculitis, leading to a diagnostic delay of months to years. We describe here a 7-year-old boy who presented with a history of prolonged fever and multiple focal neurologic deficits, which were being treated as CNS tuberculosis at the referring hospital. In view of the relapsing course with multiple areas of hemorrhagic tumefactive lesions on neuroimaging, the diagnosis was revised to acquired demyelination, and he received multiple cycles of immunotherapy. A brain biopsy was inconclusive. Subsequently, 13 months after disease onset, the child presented with features of systemic HLH in the form of fever, pancytopenia, splenomegaly, elevated ferritin, and triglycerides. Primary HLH was suspected, and genetic testing revealed a likely pathologic compound heterozygous variation in the PRF1 gene confirming the diagnosis. We planned a hematopoietic stem cell transplant as definitive therapy, but the child succumbed to an episode of sepsis and aspiration pneumonia. We infer from this case that primary HLH is a great mimicker. A high index of suspicion is required to establish a timely diagnosis. Primary HLH may stay isolated to CNS for months and should be considered in the differential diagnosis of all refractory cases of demyelination.

TiO2-SiO2 Self-Standing Materials bearing Hierarchical Porosity: MUB-200(x) Series toward 3D-Efficient VOC Photoabatement Properties.

Three-dimensional photoactive self-standing porous materials have been synthesized through the integration of soft chemistry and colloids (emulsions, lyotrope mesophases, and P25 titania nanoparticles). Final multiscale porous ceramics bear 700-1000 m2 g-1 of micromesoporosity depending on the P25 nanoparticle contents. The applied thermal treatment does not affect the P25 anatase/rutile allotropic phase ratio. Photonic investigations correlated with the foams' morphologies suggest that the larger amount of TiO2 that is introduced, the larger the walls' density and the smaller the mean size of the void macroscopic diameters, with both effects inducing a reduction of the photon transport mean free path (lt) with the P25 content increase. A light penetration depth in the range of 6 mm is reached, thus depicting real 3D photonic scavenger behavior. The 3D photocatalytic properties of the MUB-200(x) series, studied in a dynamic "flow-through" configuration, show that the highest photoactivity (concentration of acetone ablated and concentration of CO2 formed) is obtained with the highest monolith height (volume) while providing an average of 75% mineralization. These experimental results validate the fact that these materials, bearing 3D photoactivity, are paving the path for air purification operating with self-standing porous monolith-type materials, which are much easier to handle than powders. As such, the photocatalytic systems can now be advantageously miniaturized, thereby offering indoor air treatment within vehicles/homes while drastically limiting the associated encumbrance. This volumetric counterintuitive acting mode for light-induced reactions may find other relevant advanced applications for photoinduced water splitting, solar fuel, and dye-sensitized solar cells while both optimizing photon scavenging and opening the path for the miniaturization of the processes where encumbrance or a foot-print penalty would be advantageously circumvented.