Systemic inflammatory syndrome in COVID-19-SISCoV study: systematic review and meta-analysis.

BACKGROUND: There has been a recent upsurge in the cases of Multisystem inflammatory syndrome in children (MIS-C) associated with Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis on the demographic profile, clinical characteristics, complications, management, and prognosis of this emerging novel entity. METHODS: Using a predefined search strategy incorporating MeSH terms and keywords, all known literature databases were searched up till 10th July 2020. The review was done in accordance with PRISMA guidelines and registered in PROSPERO (CRD4202019757). RESULTS: Of the 862 identified publications, 18 studies comprising 833 patients were included for meta-analysis. The socio-demographic profile showed male predilection (p = 0.0085) with no significant racial predisposition. A higher incidence of gastrointestinal symptoms (603/715, 84.3%), myocarditis (191/309, 61.8%), left ventricular dysfunction (190/422, 45.0%), pericardial (135/436, 31.0%) and neurological symptoms (138/602, 22.9%) was reported. Serological evidence of SARS-CoV-2 had higher sensitivity compared to rtPCR (291/800, 36.4% vs 495/752, 65.8%; p < 0.001). Coronary artery anomaly (CAA) was reported in 117/681 in 9 publications (17.2%). A total of 13 (1.6%) fatalities were reported. CONCLUSION: Clinicians need to be vigilant in identifying the constellation of these symptoms in children with clinical or epidemiologic SARS-CoV-2 infection. Early diagnosis and treatment lead to a favorable outcome. IMPACT: Key message This review analyses the demographic profile, clinical spectrum, management strategies, prognosis, and pathophysiology of MIS-C among children with SARS-CoV-2 infection. The stark differences of MIS-C from Kawasaki disease with respect to demographics and clinical spectrum is addressed. Over-reliance on rtPCR for diagnosis can miss the diagnosis of MIS-C. New addition to existing literature The first systematic review and meta-analysis of published literature on MIS-C associated with COVID-19. IMPACT: The article will serve to spread awareness among the clinicians regarding this emerging novel entity, so that diagnosis can be made early and management can be initiated promptly.

Disorders of Tetrahydrobiopterin Metabolism: Experience from South India.

BACKGROUND: Disorders of tetrahydrobiopterin metabolism represent a rare group of inherited neurotransmitter disorders that manifests mainly in infancy or childhood with developmental delay, neuroregression, epilepsy, movement disorders, and autonomic symptoms. METHODOLOGY: A retrospective review of genetically confirmed cases of disorders of tetrahydrobiopterin metabolism over a period of three years (Jan 2018 to Jan 2021) was performed across two paediatric neurology centres from South India. RESULTS: A total of nine patients(M:F=4:5) fulfilled the eligibility criteria. The genetic variants detected include homozygous mutations in the QDPR(n=6), GCH1(n=2), and PTS(n=1) genes. The median age at onset of symptoms was 6-months(range 3-78 months), while that at diagnosis was 15-months (8-120 months), resulting in a median delay in diagnosis of 9-months. The main clinical manifestations included neuroregression (89%), developmental delay(78%), dystonia(78%) and seizures(55%). Management strategies included a phenylalanine restricted diet, levodopa/carbidopa, 5-Hydroxytryphtophan, and folinic acid. Only, Patient-2 afforded and received BH4 supplementation at a sub-optimal dose later in the disease course. We had a median duration of follow up of 15 months (range 2-48 months). Though the biochemical response has been marked; except for patients with GTPCH deficiency, only mild clinical improvement was noted with regards to developmental milestones, seizures, or dystonia in others. CONCLUSION: Tetrahydrobiopterin deficiencies represent a rare yet potentially treatable cause for non-phenylketonuria hyperphenylalaninemia with better outcomes when treated early in life. Screening for disorders of biopterin metabolism in patients with hyperphenylalaninemia prevents delayed diagnosis. This study expands the genotype-phenotype spectrum of patients with disorders of tetrahydrobiopterin metabolism from South India.

"Pivoting" by food industry firms to cope with COVID-19 in developing regions: E-commerce and "copivoting" delivery intermediaries.

Coronavirus disease 2019 and related lockdown policies in 2020 shocked food industry firms' supply chains in developing regions. Firms "pivoted" to e-commerce to reach consumers and e-procurement to reach processors and farmers. "Delivery intermediaries" copivoted with food firms to help them deliver and procure. This was crucial to the ability of the food firms to pivot. The pandemic was a "crucible" that induced this set of fast-tracking innovations, accelerating the diffusion of e-commerce and delivery intermediaries, and enabling food industry firms to redesign, at least temporarily, and perhaps for the long term, their supply chains to be more resilient, and to weather the pandemic, supply consumers, and contribute to food security. We present a theoretical model to explain these firm strategies, and then apply the framework to classify firms' practical strategies. We focus on cases in Asia and Latin America. Enabling policy and infrastructural conditions allowed firms to pivot and copivot fluidly.

Experimental study of fs-laser induced sub-100-nm periodic surface structures on titanium.

In this work the formation of laser-induced periodic surface structures (LIPSS) on a titanium surface upon irradiation by linearly polarized femtosecond (fs) laser pulses with a repetition rate of 1 kHz in air environment was studied experimentally. In particular, the dependence of high-spatial-frequency-LIPSS (HSFL) characteristics on various laser parameters: fluence, pulse number, wavelength (800 nm and 400 nm), pulse duration (10 fs - 550 fs), and polarization was studied in detail. In comparison with low-spatial-frequency-LIPSS (LSFL), the HSFL emerge at a much lower fluence with orientation perpendicular to the ridges of the LSFL. It was observed that these two types of LIPSS demonstrate different fluence, shot number and wavelength dependencies, which suggest their origin is different. Therefore, the HSFL formation mechanism cannot be described by the widely accepted interference model developed for describing LSFL formation.

A typical case of myoclonic epilepsy with ragged red fibers (MERRF) and the lessons learned.

Mitochondrial diseases have a special predilection to involve the brain in view of its high metabolic demand and the tendency for the formation of excitatory neurotransmitters when there is deficiency of intracellular ATP. These diseases have a great phenotypic variation and need a high degree of suspicion. However, some specific syndromes are well defined, both genotypically and phenotypically. Some of the drugs are potentially fatal mitochondrial poisons and an insight into that may be lifesaving as well as prevent serious morbidities.We report a typical case of myoclonic epilepsy with ragged red fibers (MERRF) with classical phenotype and genotype. There was rapid multiaxial deterioration with the introduction of sodium valproate which partly reversed on introducing mitochondrial cocktail and withdrawal of the offending drug.Sodium valproate, phenobarbitone, chloramphenicol and many anti-viral agents are mitochondrial poisons that increase the morbidity and mortality in patients with mitochondrial disease. More harm to the patient can be avoided with insight into this information.

Understanding the pathophysiology of reflex epilepsy using simultaneous EEG-fMRI.

Measuring neuro-haemodynamic correlates in the brain of epilepsy patients using EEG-fMRI has opened new avenues in clinical neuroscience, as these are two complementary methods for understanding brain function. In this study, we investigated three patients with drug-resistant reflex epilepsy using EEG-fMRI. Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. The analysis of EEG-fMRI data was based on the visual identification of interictal epileptiform discharges on scalp EEG. The convolution of onset time and duration of these epilepsy spikes was estimated, and using these condition-specific effects in a general linear model approach, we evaluated activation of fMRI. Patients with startle myoclonus epilepsy experienced epilepsy in response to sudden sound or touch, in association with increased delta and theta activity with a spike-and-slow-wave pattern of interictal epileptiform discharges on EEG and fronto-parietal network activation pattern on SPECT and EEG-fMRI. Eating epilepsy was triggered by sight or smell of food and fronto-temporal discharges were noted on video-EEG (VEEG). Similarly, fronto-temporo-parietal involvement was noted on SPECT and EEG-fMRI. Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement. SPECT and EEG fMRI revealed a similar fronto-parietal-occipital involvement. From these results, we conclude that continuous EEG recording can improve the modelling of BOLD changes related to interictal epileptic activity and this can thus be used to understand the neuro-haemodynamic substrates involved in reflex epilepsy.

'The spectrum of vascular dementia'--a retrospective study from South India.

OBJECTIVES: Vascular dementia (VaD) is high in Indian population and is preventable to some extent but there is paucity of literature. Hence we decided to study the clinical and laboratory spectrum of VaD. METHODS: It was retrospective hospital based study. The patients who satisfied Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV criteria) for VaD and age of more than 40 years were identified on the basis of case file code which is uniformly used by the hospital. RESULTS: Of the 83 patients included, 72.3% (60) were males (mean age: 65.3 ± 8.6 years) and 27.3% (23) females (mean age: 65.7 ± 1.1 years). Mean age of the patients was 65.4 ± 9.2 years. Abrupt onset was seen in 42 (51%) patients and 41 (49%) had insidious onset. There was gradual progression in 48 (57.8%), stepwise progression in 33 (39.8%) and 2 patients had rapid progression. Naming impairment was seen in 64 (77.1%), visuospatial disorientation was present in 49 (59%), dyscalculia in 55 (66.3%), emotional lability in 26.5%. Hypertension was the single most important risk factor (71.1%) followed by smoking (46.9%) and dyslipidaemia (45.8%). Neuropsychological testing showed Executive function involvement in 18 (66.7%) followed by memory in 16 (59.3%) patients. The total white matter hyperintensity score (12.39 ± 6.73) significantly correlated with mini mental scores (r: -0.4; p: 0.02). CONCLUSION: We found that in our patients with vascular dementia, gradual progression, naming impairment and small vessel disease in imaging were the most common abnormalities. Hypertension was the single most important risk factor.

Encephalopathy in critically ill patients.

Potentially reversible encephalopathies do add to the morbidity and mortality in critically ill patients. They are commonly seen in patients above 50 years between the 6th to 20th day of illness. Wernicke's encephalopathy, osmotic demyelination, hypoglycemia and other less common conditions like non-convulsive status, cerebral venous thrombosis and acute disseminated encephalomyelitis should be looked for in the appropriate setting as to facilitate early treatment.

Rare treatable limb girdle muscle disease.

We report two cases of Limb Girdle pattern of muscle weakness caused by hyperparathyroidism due to parathyroid adenoma. It can be easily missed as early symptoms are non specific but once diagnosed it is easily treatable and complete recovery occurs over a period of time.

Spectrum of Clinical and Imaging Characteristics of 48 X-Linked Adrenoleukodystrophy Patients: Our Experience from a University Hospital.

Background and Objectives: X-linked adrenoleukodystrophy (X-ALD) occurs due to the mutation in the ABCD1-gene. Our study was to correlate the clinical, radiological, and biochemical features in a cohort of X-ALD patients. Methods: We retrospectively analyzed 48 (M: F: 47:1) biochemically confirmed cases of X-ALD, classified them as cerebral ALD (childhood, adolescent, and adult), adrenomyeloneuropathy, Addisonian only. The Magnetic Resonance Imaging (MRI) of the radiological patterns was classified based on Loes classification. Results: The various clinical phenotypes were childhood cerebral X-ALD (58.3%), adolescent cerebral X-ALD (14.6%), adult-cerebral X-ALD (20.8%), Addisonian variant (4.2%), and adrenomyeloneuropathy (AMN) (2.1%). The imaging features were posterior white matter (Pattern-1) observed in 33 (68.75%) patients, cerebellar white matter (Pattern-4) noted in 5 subjects, anterior white matter (Pattern-2) observed in 3 patients, combined parieto-occipital and frontal white matter (Pattern-5) observed in 3 patients, isolated projection fiber (Pattern-3) observed in 1 patient. Rare features of the involvement of optic tract, anterior and lateral columns of cervicodorsal cord, bilateral central tegmental tracts, basal ganglia, and tigroid appearance were observed. Interpretation: This is a comprehensive clinical, biochemical, and imaging analysis with follow-up information of one of the largest series of X-ALD patients. The knowledge regarding the clinical features, typical and atypical imaging patterns is of vital importance for early diagnosis and treatment.

Two cases of a rare treatable limb girdle muscle disease.

We report two cases of limb girdle pattern of muscle weakness caused by hyperparathyroidism due to parathyroid adenoma. It can be easily missed as early symptoms are non specific but once diagnosed it is easily treatable and complete recovery occurs over a period of time.

Circuit modeling of the transmissivity of stacked two-dimensional metallic meshes.

This paper presents a simple analytical circuit-like model to study the transmission of electromagnetic waves through stacked two-dimensional (2-D) conducting meshes. When possible the application of this methodology is very convenient since it provides a straightforward rationale to understand the physical mechanisms behind measured and computed transmission spectra of complex geometries. Also, the disposal of closed-form expressions for the circuit parameters makes the computation effort required by this approach almost negligible. The model is tested by proper comparison with previously obtained numerical and experimental results. The experimental results are explained in terms of the behavior of a finite number of strongly coupled Fabry-Pérot resonators. The number of transmission peaks within a transmission band is equal to the number of resonators. The approximate resonance frequencies of the first and last transmission peaks are obtained from the analysis of an infinite structure of periodically stacked resonators, along with the analytical expressions for the lower and upper limits of the pass-band based on the circuit model.

X-Linked Myopathy with Excessive Autophagy; A Case Report.

X-linked myopathy with excessive autophagy (XMEA) is a rare, slowly progressive muscle disease characterized by membrane-bound sarcoplasmic vacuoles distinct from other forms of myopathies with vacuoles. We report this rare condition in a 5-year-old boy with proximal muscle weakness and morphological evidence of autophagic vacuoles.

A clinical TRIAD for early suspicion of autoimmune encephalitis as a possibility in patients presenting with progressive cognitive decline.

Patients with progressive cognitive decline mostly suffer from degenerative disease and carry a relatively poor prognosis. But small groups among these patients have a potentially treatable cause of illness and therefore every patient with dementia needs to be considered treatable unless proved otherwise. This group can be identified only by high degree of suspicion based on clinical clues. We have evaluated the validity of some simple clinical clues which we noticed in our patients with immune mediated dementias. The Panic score, Epsworth sleepiness score, catatonic symptoms and history of seizures were compared between 23 and 11 patients with serologically confirmed anti-NMDA antibody and anti-VGKC antibody associated encephalitis respectively. They were compared with 20 patients with probable behavioral variant of Frontotemporal dementia (bvFTD) and 20 patients with probable Alzheimer's disease (AD). Chi-square test was used to compare across the groups and there was significant difference (P < 0.05) across the 4 groups comprising anti NMDA encephalitis, anti VGKC encephalitis, FTD and AD among the four variables (Panic scores, Catatonic symptoms, Epsworth sleepiness score and seizures) studied. Our study revealed that panic and sleepiness is highly significant when tested across all groups and catatonia showed a trend towards NMDA and when compared with degenerative dementia versus immune mediated syndromes all the 4 parameters were highly significant This simple bedside TRIAD of panic, sleepiness with either of catatonia or seizures if found in patients it is appropriate to order antibody assessment before anything else is planned. This needs to be evaluated in a larger sample.

Flavonoids: an overview.

Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.

Neuropsychological profile in early Parkinson's disease: Comparison between patients with right side onset versus left side onset of motor symptoms.

AIMS: Though impaired cognition in Parkinson's disease (PD) is well known, data in early PD is sparse. This study was designed to assess the cognitive profile in patients with early PD (motor symptoms <5 years and Hoehn and Yahr stage <2), and to compare the cognitive profile between these patients with right versus left side onset of motor symptoms. MATERIALS AND METHODS: National Institute of National Health and Neurosciences (NIMHANS) neuropsychological battery was used to assess the cognitive profile in 50 patients with early PD and compared with 50 age-, education-, and gender-matched healthy controls. Within the PD group, the cognitive profile was also compared between patients with right side onset motor symptoms (RPD) versus those with left side onset (LPD). The neuropsychological tests assessed the executive functions, memory, attention, visuospatial functions, and psychomotor speed. RESULTS: Among the 50 patients, 25 each were RPD and LPD. The two subgroups were matched for age, gender, education, age at disease onset, disease duration, and degree of motor disability. There was no significant difference between the groups on Hoehn and Yahr staging or Unified Parkinson Disease Rating Scale (UPDRS) motor score. Patients with early PD performed significantly worse in the tasks involving memory, executive functions, and attention compared to controls. However, there was no difference in the cognitive profile between RPD and LPD subgroups. CONCLUSIONS: Patients with early PD have cognitive dysfunction with predominant involvement of frontal and temporal lobes. Side of onset of motor symptoms probably does not have significant role in future development or profile of cognitive dysfunction in PD.

Genome Analysis of Osteosarcoma Progression Samples Identifies FGFR1 Overexpression as a Potential Treatment Target and CHM as a Candidate Tumor Suppressor Gene.

Osteosarcoma (OS) is the most common primary malignant tumor of bone, showing complex chromosomal rearrangements but with few known consistent changes. Deeper biological understanding is crucial to find new therapies to improve patient survival. We have sequenced the whole exome of two primary tumors (before and after chemotherapy), one metastatic tumor and a matched normal sample from two OS patients, to identify mutations involved in cancer biology. The metastatic samples were also RNA sequenced. By RNA sequencing we identified dysregulated expression levels of drug resistance- and apoptosis-related genes. Two fusion transcripts were identified in one patient (OS111); the first resulted in p53 inactivation by fusing the first exon of TP53 to the fifth exon of FAM45A. The second fusion joined the two first exons of FGFR1 to the second exon of ZNF343. Furthermore, FGFR1 was amplified and highly expressed, representing a potential treatment target in this patient. Whole exome sequencing revealed large intertumor heterogeneity, with surprisingly few shared mutations. Careful evaluation and validation of the data sets revealed a number of artefacts, but one recurrent mutation was validated, a nonsense mutation in CHM (patient OS106), which also was the mutation with the highest expression frequency (53%). The second patient (OS111) had wild-type CHM, but a downregulated expression level. In a panel of 71 clinical samples, we confirmed significant low expression of CHM compared to the controls (p = 0.003). Furthermore, by analyzing public datasets, we identified a significant association between low expression and poor survival in two other cancer types. Together, these results suggest CHM as a candidate tumor suppressor gene that warrants further investigation.