Primary amoebic meningoencephalitis in children- report of two cases from South India.

Primary Amoebic meningoencephalitis is a rare and fatal neuro-infection caused by free-living fresh-water amoeba Naegleria fowleri. It is a ubiquitous organism and the infection occurs usually via contact with warm water-bodies. The clinical presentation is often indistinguishable from acute bacterial meningitis and the diagnosis can be made by CSF wet smear examination if there is a high index of suspicion. The disease progresses rapidly compared to pyogenic meningitis and usually has a fatal outcome. Reports of two confirmed cases of primary amoebic meningoencephalitis in children from different centres in Kerala state of India are presented here. In spite of early diagnosis and treatment, both these patients demised. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of acute meningitis, especially in patients with recent freshwater exposure. Implementation of chlorination of pools of water bodies, especially if re-opened for recreational purpose after prolonged periods of non-use, needs vigorous implementation.

Identification of Alzheimer associated differentially expressed gene through microarray data and transfer learning-based image analysis.

Major factors contribute to mental stress and enhance the progression of late-onset Alzheimer's disease (AD). The factors that lead to neurodegeneration, such as tau protein hyperphosphorylation and increased amyloid-beta production, can be mimicked in animal stress models. The present study identifies differentially expressed genes (DEGs) data and its corresponding predictive image analysis in rat models. The gene expression profile of GSE72062, GSE85162, GSE143951 and GSE85238 was downloaded from NCBI, GEO archive to analyse DEGs. Functional enrichment and pathway relationship networks, gene signal, protein interaction and micro-RNA interaction DEGs networks were constructed and investigated. The image analysis of histopathological slides of rat brain images corresponding to AD microarray-based DEGs profile was undertaken using the convolution neural networks (ConvNets) model. Enrichment of network in terms of GO concluded with 10 DEGs, namely ARHGAP32, GNA11, NR5A1, GNAT3, FOSL1, HELZ2, NMUR2, BDKRB1, RPL3L and RPL39L as potential gene targets to control neurodegeneration and progression of sporadic AD. The image analysis of AD microarray-based DEGs profile builds a successful predictive model of 89% and 61% training and test accuracy with a minimum of 2.480% loss using transfer learning, VGG16 model. Interestingly, the ARHGAP32 gene, a Rho GTPase activating class, was identified to have a functional relationship with two significant genes BCL2 and MMP9, that are well explored in AD. The current investigation upgrades the traditional pre-clinical AD research using microarray data analysis and ConvNets. The model successfully predicts DEG from histopathology slides of rat brain samples, paving the way for image analysis to determine the underlying molecular makeup of the test samples.

COVID-19 related multisystem inflammatory syndrome in children (MIS-C): a hospital-based prospective cohort study from Kerala, India.

Objectives: To study (1) epidemiological factors, clinical profile and outcomes of COVID-19 related multisystem inflammatory syndrome in children (MIS-C), (2) clinical profile across age groups, (3) medium-term outcomes and (4) parameters associated with disease severity. Design: Hospital-based prospective cohort study. Setting: Two tertiary care centres in Kerala, India. Participants: Diagnosed patients of MIS-C using the case definition of Centres for Disease Control and Prevention. Statistical analysis: Pearson χ2 test or Fisher's exact test was used to compare the categorical variables and independent sample t-test or Mann-Whitney test was used to compare the continuous variables between the subgroups categorised by the requirement of mechanical ventilation. Bonferroni's correction was used for multiple comparisons. Results: We report 41 patients with MIS-C, mean age was 6.2 (4.0) years, and 33 (80%) were previously healthy. Echocardiogram was abnormal in 23 (56%), and coronary abnormalities were noted in 15 (37%) patients. Immunomodulatory therapy was administered to 39 (95%), steroids and IVIg both were used in 35 (85%) and only steroids in 3 (7%) patients. Intensive care was required in 36 (88%), mechanical ventilation in 8 (20%), inotropic support in 21 (51%), and 2 (5%) patients died. Mechanical ventilation requirement in MIS-C was associated with hyperferritinaemia (p=0.001). Thirty-seven patients completed 3 months follow-up by April 2021, of whom 6 (16%) patients had some residual echocardiographic changes. Conclusions: Patients with MIS-C in our cohort had varied clinical manifestations ranging from fever with mild gastrointestinal and mucocutaneous involvement to fatal multiorgan dysfunction. Immediate and medium-term outcomes remain largely excellent except for the echocardiographic sequelae in a few patients which are also showing a resolving trend. Hyperferritinaemia was associated with the requirement of mechanical ventilation.

Multisystem Inflammatory Syndrome with Features of Atypical Kawasaki Disease during COVID-19 Pandemic.

There is a global concern of increasing number of children presenting with inflammatory syndrome with clinical features simulating Kawasaki disease, during ongoing COVID-19 pandemic. The authors report a very similar case of 5-y-old boy from a COVID-19 hotspot area who presented in late April 2020 with acute febrile illness with abdominal pain and loose stools followed by shock. On examination, child had bulbar conjunctivitis and extremity edema. Initial investigations showed high inflammatory parameters, elevated serum creatinine and liver enzymes. Echocardiography showed moderate LV dysfunction and normal coronaries. Cardiac enzymes were also elevated, suggesting myocarditis. He was treated with inotropic support, respiratory support with high flow nasal cannula, IV immunoglobulins, aspirin, steroids and diuretics. RT PCR for SARS-CoV-2 was negative twice. His clinical condition improved rapidly, was afebrile from day 2, inflammatory parameters decreased, left ventricular function improved and was discharged after 6 d of hospital stay.

Paracrine factors secreted by umbilical cord-derived mesenchymal stem cells induce angiogenesis in vitro by a VEGF-independent pathway.

Improvement in angiogenesis using mesenchymal stem cells (MSCs) is evolving as an option in patients with vascular insufficiencies. The paracrine factors secreted by MSCs have been attributed to the angiogenic response. This study was conducted to identify the factors secreted by umbilical cord-derived MSCs (UCMSCs) that might play a role in angiogenesis. To this aim, we evaluated the presence of well known proangiogenic factors in the conditioned media (CM) derived from UCMSCs by ELISA. While vascular endothelial growth factor (VEGF), a well known angiogenic factor, was not detected in the CM, gene expression was nevertheless detected in these cells. Further investigations revealed the presence of soluble VEGF receptors (sVEGF-R1 and R2) that were capable of neutralizing exogenous VEGF. Human umbilical cord vein-derived endothelial cells exposed in vitro to CM, in comparison to control media, showed improved migration (P<0.007) and capillary-like network formation (P<0.001) with no significant change in endothelial cell proliferation. The angiogenic response observed with the paracrine factors secreted by UCMSC could be due to the presence of significant levels of a metalloprotease and matrix metalloproteases-2 (237.4±47.1 ng/10(6) cells). Data suggest that a VEGF-independent pathway is involved in the angiogenic response observed with endothelial cells in the presence of UCMSC-CM.