New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.

Risk factors and outcome of acute kidney injury in children with snake envenomation.

Our study evaluates the risk factors of acute kidney injury (AKI) in children with snake envenomation. Out of 145 cases, 54 (37%) developed AKI. Unsurprisingly, the mortality increased with oliguria and higher levels of creatinine. Bleeding manifestations were also more common among the AKI group.

Synthesis of CeO2/ZrO2/ZnO nano alloy oxide and investigation of photocatalysis of naphthol orange under sunlight.

Novel metal-like cerium- and zirconium-doped ZnO photocatalysts were prepared herein with various proportions of molar ratios via a cost-effective co-precipitation method. The effects of novel metal doping on the photocatalytic activity of ZnO were studied. Various techniques were used to investigate the structural, morphological, and elemental composition, particle size, optical properties, and catalytic activity of the synthesized photocatalysts. It was found that the crystallite size and particle size of the nano alloy oxides were 15.12 ± 1 and 5 ± 1 nm, respectively, and the surface morphology of the nanoparticles indicated a satisfactory surface area. Among all synthesized nanocomposites, CexZrxZnxO5 (x = 1) [CZ1Z2-A] exhibited satisfactory photo-oxidation activity against naphthol orange (NO) under sunlight with a rate constant of 57.5 × 10-3 min-1. The effects of pH, inorganic salts, dye concentrations, and catalytic dosage on NO degradation were studied. A probable mechanistic pathway for the degradation of NO in the presence of CZ1Z2-A was proposed, and studies of sacrificial agents indicated that superoxide radical anion (O2˙-) was the main accountable active species in NO degradation. In addition, CZ1Z2-A exhibited excellent recyclability potential, and XRD studies revealed that there was no change in the crystal structure before or after degradation, which indicated its high stability. The intriguing finding was that Ce- and Zr-doped ZnO did not exhibit satisfactory catalytic performance in the photo-oxidation of NO. However, the composite formula of CexZrxZnxO5 (x = 1) with a 1 : 1 : 1 ratio of metal ions offered excellent catalytic activity.

Label-Free Detection of Epinephrine Using Flower-like Biomimetic CuS Antioxidant Nanozymes.

A biosensor comprising crystalline CuS nanoparticles (NPs) was synthesized via a one-step simple coprecipitation route without involvement of a surfactant. The powder X-ray diffraction method has been used to evaluate the crystalline nature and different phases consist of the formation of CuS NPs. Mainly hexagonal unit cells consist of the formation of CuS NP unit cells. Most of the surfaces are covered with rhombohedral microparticles with a smooth exterior and surface clustering, examined by SEM images, and the shape of NPs was spherical, having an average size of 23 nm, as confirmed by TEM analysis. This study has focused on the peroxidase-mimicking activity, superoxide dismutase (SOD)-mimicking activity, and chemosensor-based colorimetric determination and detection of epinephrine (EP) neurotransmitters with excellent selectivity. The CuS NPs catalyzed the oxidation of the oxidase substrate 3, 3-5, 5 tetramethyl benzidine (TMB) with the help of supplementary H2O2 that followed Michaelis-Menten kinetics with excellent Km and Vmax values calculated by the Lineweaver-Burk plot. Taking advantage of the drop in absorbance upon introduction of EP for the CuS NPs-TMB/H2O2 system, a colorimetric route has been developed for selective and real-time detection of EP. The sensitivity of the new colorimetric probe was vibrant, having a linear range of 0-16 µM, and achieved a low limit of detection of 457 nM. Moreover, the present nanosystem exhibited appreciable SOD-mimicking activity which could effectively remove O2•- from commercial cigarette smoke, along with it acting as a potential radical scavenger as well. The new nanosystem effectively scavenged •OH, O2.-, and metal chelation which were investigated calorimetrically.

Comparison between Phenobarbitone and Levetiracetam as the initial anticonvulsant in preterm neonatal seizures - a pilot randomized control trial in developing country setup.

This study aimed to compare the efficacy and safety of intravenous Levetiracetam and Phenobarbitone in the treatment of seizures in preterm neonates. It was an open-labeled, parallel randomized controlled trial conducted in a tertiary Neonatal Intensive Care Unit, India. Total 48 preterm neonates (28-36+6 weeks) with clinical seizures were randomized to receive either Levetiracetam (LEV; 40 mg/kg, then 20 mg/kg) or Phenobarbitone (PB; 15 mg/kg, then 10 mg/kg) intravenously as first loading dose in ratio 1:1; second loading was given for persistent seizure. Efficacy was denoted by cessation of clinical seizures with first or second doses of the allotted antiepileptic, and remaining seizure-free for the next 24 h. The demographic characteristics of preterm neonates and seizure types were comparable between both groups. Clinical seizure was controlled in 19 (79%) neonates in LEV group and 17 (70%) neonates in PB group, RR 1.12 (95% CI: 0.80 to 1.55), p = 0.504. There was increased respiratory support in PB group 9 (38%) vs. 3 (13%) in LEV group, RR 3.0 (95% CI: 0.92 to 9.74), p = 0.06.  Conclusion: Levetiracetam and Phenobarbitone were equally efficacious for clinical neonatal seizure control, but increased respiratory support was found with Phenobarbitone use. What is Known: • Preterm neonates are at higher risk of neonatal seizure and Phenobarbitone is commonly used as the first line antiepileptic drugs in treating them. What is New: • Levetiracetam found equally efficacious as Phenobarbitone for cessation of clinical seizures in preterm neonates, with less adverse effect.

Exudation of microplastics from commonly used face masks in COVID-19 pandemic.

The COVID-19 pandemic forced use of face masks up to billions of masks per day globally. Though an important and necessary measure for control of the pandemic, use of masks also poses some inherent risks. One of those risks is inhalation of microplastics released from the mask materials. Since most of the mask materials are made from plastic/polymers, they always have the potential to expose the user to fragmented microplastics. To estimate the amount of inhalable microplastic exuded from masks, an experiment simulating real-life scenario of mask usage was performed. The study included collection of microplastics oozed out from the masks on to a filter paper followed by staining and fluorescence detection of the total number of microplastics using a microscope. Both used and new masks were studied. Based on the emission wavelength, the microplastics were found to be belonging to three different categories, namely blue, green and red emitting microplastics respectively. The number of microplastic particles emitted per mask over a period of usage of 8 h was about 5000 to 9000 for new masks and about 6500 to 15,000 for used masks respectively. The estimation of polymer type of plastic in the mask fabrics was also carried out using Raman and FTIR spectroscopy.

Antiphospholipid Antibody Syndrome in Childhood Systemic Lupus Erythematous With a Unique Presentation: A Case Report.

Initial presentation of childhood systemic lupus erythematosus (SLE) as antiphospholipid syndrome (APS) is uncommon; moreover, APS presenting with both hemorrhage and thrombosis is very rare. We report a case of a previously healthy eight-year-old boy, without any significant past or family history, who presented with ecchymotic patches, epistaxis, and right-side hemiparesis. Investigation showed severe thrombocytopenia and isolated high activated partial thromboplastin time (aPTT) not corrected by mixing study. During his hospital stay, the child developed left-sided focal seizure and digital gangrene as thrombotic events. Neuroimaging revealed initially hemorrhagic stroke and subsequently bilateral infarct of middle cerebral artery (MCA) territory. The child was diagnosed as a case of SLE with APS based on Systemic Lupus International Collaboration Clinics (SLICC) criteria, revised APS classification, clinicoimmunological profile and neuroimaging. As the child was progressing towards catastrophic APS, he was treated aggressively with intravenous pulse methylprednisolone, intravenous cyclophosphamide and plasmapheresis with successful recovery. A simple bleeding manifestation may mask a serious disorder. A simple test like mixing study is helpful in diagnosis and in avoiding unnecessary investigations. A combination of both hemorrhage and thrombosis is an unusual presentation of APS and should always be suspected in case of autoimmune disorder, especially in SLE.

A rare case of acute abdomen in a child with scrub typhus.

Acalculous cholecystitis and pancreatitis are rare complications of scrub typhus in children. In febrile patients from an endemic area with multisystem involvement, scrub typhus should be a differential diagnosis. Scrub typhus patients who develop abdominal pain, acute cholecystitis or pancreatitis should be suspected.

Clinico-Biochemical Profile and Identification of Independent Risk Factors of Frequent Relapse in Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Background and aim Nephrotic syndrome is one of the commonest glomerular diseases in children, and the majority of them have minimal change lesions in histology with a favorable outcome. Most children with minimal change disease (MCD) are steroid-sensitive, but half of them have a frequent relapse and a prolonged course. This study was conducted to evaluate the clinical manifestations and biochemical profile and to determine independent risk factors of frequent relapse in children with steroid-sensitive nephrotic syndrome (SSNS). Methods This was a tertiary care hospital-based observational study conducted at the pediatric department of Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from October 2017 to September 2019. Fifty-three children from age one to 15 years admitted with steroid-sensitive nephrotic syndrome diagnosed as per the International Study of Kidney Disease in Children (ISKDC) criteria were enrolled in the study. On admission, history-taking, physical examination, and routine hematological and biochemical tests were carried out. Children who had no infection were started oral prednisolone at the dose of 2 mg/kg/day for six weeks, followed by 1.5 mg/kg/day on alternate days for six weeks with daily follow-up for evidence of proteinuria till remission. The parameters evaluated were age at presentation, sex, type of presentation, precipitating factors, laboratory findings, and rapidity of steroid response. All children were followed up for one year, and those with no relapse over a period of one year after remission served as the control group to determine the risk factors for relapse. Data were analyzed using standard statistical software (Stata version 13.1, StataCorp LLC, College Station, Texas, USA). Results Of the 53 cases, 47% of the children had a relapse. In the relapse category, 88% were male, and 67% were between one and 5.5 years. The clinical manifestations during the first episode in the relapse group were similar to the no relapse group. Investigations revealed that 64% of the children with relapse had serum total protein ≤ 4.2 g/dL (p = 0) and that 59% had serum albumin ≤ 1.8 g/dL (p = 0.004). In the relapse group, 41% of the children went into remission within two weeks of initiation of therapy as compared with 80% in the no relapse group. Conclusion The risk factors determined for relapse in SSNS are male sex, younger age, low serum albumin, low serum total protein, and delayed response to steroid therapy.

High Myopia: A Pointer of an Inborn Error of Metabolism.

An 11-year-old boy with marfanoid habitus and high myopia presented with multiple episodes of seizures. He was found to have arachnodactyly, hypermobile joints, ectopia lentis, cerebral venous sinus thrombosis (CVST) with very high serum methionine and homocysteine. Genetic evaluation unveiled homocystinuria due to cystathionine beta-synthase deficiency. The patient was treated with high-dose pyridoxine, methionine restricted diet, anticonvulsants, warfarin, and correction of ectopia lentis. Homocystinuria should be suspected in patients with tall stature and pathological myopia. Early treatment can prevent thromboembolic complications.

Elemental analysis of residual ash generated during plasma incineration of cellulosic, rubber and plastic waste.

Management of plastic, rubber and cellulosic waste from various industries is a challenging task. An engineering scale plasma pyrolysis based incinerator has been commissioned for incineration of combustible waste, including plastic, rubber and cellulose. Operational trials of wastes with simulated composition show a weight reduction factor of more than 18 and volume reduction factor of more than 30. The volume reduction factor is tenfold higher than the compaction process currently practised for rubber and plastic wastes. Representative residual ash samples derived from these runs are subjected to their elemental analysis using EDXRF technique and results are comparable with the published literature. Relative variation of individual elements is attributed to the type of waste and feed composition. Analysis is aided with the calculation of index of geoaccumulation, enrichment factor (EF), contamination factor (CF) and pollution load index (PLI). From this study, it is evident that S, Cr, Zn, As, Se, Hg and Pb are of concern for environment in residual ash from plasma incineration of combustible waste. The efficacy of the incineration process is evaluated; C, H and O reduction achieved is more than 98% and overall enrichment ratio (ER) for the inorganic elements is more than 4.5. This study highlights the importance of elemental composition for the performance analysis of the plasma based incineration as well as hazards evaluation of constituents in residual ash for its further management.

Catalytic Use toward the Redox Reaction of Toxic Industrial Wastes in Innocuous Aqueous Medium and Antibacterial Activity of Novel Cu x Ag x Zn1-2x O Nanocomposites.

In this work, we report the redox properties in organic catalytic transformation and antibacterial activity of novel Cu x Ag x Zn1-2x O nanocomposites. Cu- and Ag-doped ZnO [Cu x Ag x Zn1-2x O (x = 0.1)] (CAZ), Cu-doped ZnO [Cu x Zn1-x O (x = 0.1)] (CZ), and Ag-doped ZnO [Ag x Zn1-x O (x = 0.1)] (AZ) were prepared via a chemical co-precipitation method. The synthesized nanocomposites were characterized using different spectroscopic techniques. The catalytic activity of CAZ, CZ, and AZ was examined for the reduction of 4-nitrophenol (4-NP) and 4-nitroaniline (4-NA) in the presence of NaBH4 in an aqueous medium. The photocatalytic oxidation efficiency of these catalysts was also observed against naphthol orange (NO) under ultraviolet light. It was found that the catalytic reduction and oxidation efficiency of CAZ is higher than that of CZ and AZ in 4-NP/4-NA and NO in a water solvent, respectively. The antibacterial property of CAZ was also studied against Gram-positive and Gram-negative bacteria by agar well diffusion and the minimum inhibitory concentration methods. It was found that CAZ shows better antimicrobial activity compared to its parental Cu(NO3)2·3H2O, AgNO3, and ZnO. Therefore, the incorporation of Cu and Ag into ZnO increases its catalytic and antimicrobial activity remarkably. Fourier-transform infrared and X-ray diffraction (XRD) studies of CAZ indicate the incorporation of Cu and Ag into the lattice of ZnO. The phase structure of CAZ was wurtzite hexagonal, and the average crystallite size was 93 ± 1 nm measured from XRD. The average grain size and particle size of CAZ were found to be 200 and 100 ± 5 nm originating from SEM and transmission electron microscopy studies, respectively. The optical energy band gap of CAZ is 3.15 eV, which supports the excellent photocatalyst under UV light. CAZ also exhibits good agreement for photoluminescence properties with a high intensity peak at 571 nm, indicating surface oxygen vacancies and defects which might be responsible for higher photocatalytic activity compared to others. The nanocomposite shows excellent reusability without any significant loss of activity.

Prevalence of Allergic Sensitization in Childhood Asthma.

Introduction The allergic sensitization in childhood asthma is common and the prevalence varies in different geographical locations. The data on allergen sensitization to guide clinicians on allergy avoidance is limited. Method This prospective observational study was conducted between October 2019 and April 2020 on children aged two to 14 years attending an outpatient clinic. Those with recurrent wheezing or physician-diagnosed asthma were interviewed; eosinophil count, total serum immunoglobulin E (IgE) was measured; and skin prick test (SPT) was done using standardized reagents. Wheal size of ≥3mm was considered positive. Results A total of 80 children were enrolled. The mean age was 71.15 ± 33.52 months (M:F ratio =1.96:1). Allergic rhinitis, conjunctivitis, and dermatosis were seen in 76 (95.0%), 33 (41.3%), and 22 (27.5%) cases, respectively. The mean absolute eosinophil count was 576 ± 427per cmm. The mean total IgE was 800.9 ± 883.2IU/ml. Seasonal and diurnal variations were found in 34 (42.5%) and 79 (98.8%) cases. Out of 1753 skin pricks using 27 reagents, 355 (20.25%) were positive. Increasing age was significantly associated with increasing SPT positivity (P = 0.0001). The most common sensitive aeroallergens were Kentucky bluegrass (25%), Dermatophagoides pteronyssinus (22.5%), Dermatophagoides farinae (21.3%), Timothy grass, and Alternaria alternans (20% each). The most common sensitive food allergens were spinach (25%), banana (22.5%), carp (20%), shrimp and hen's egg (18.8% each), and cow's milk (17.5%). Conclusion Increasing age was associated with increasing SPT positivity in childhood asthma. The most common sensitive aeroallergens were Kentucky bluegrass and Dermatophagoides pteronyssinus; spinach and banana were the most common food allergen.

Clinical Manifestations and Outcome of Scrub Typhus in Infants From Odisha.

OBJECTIVE: To study manifestations and outcome of scrub typhus in infants. METHODS: Case record analysis of infants with scrub typhus admitted to a tertiary care hospital, diagnosed by IgM ELISA from January 1, 2016 to December 31, 2019. RESULTS: Out of 374 children diagnosed with scrub typhus, 34 (9%) were infants. Chief presentation were fever 34 (100 %), feeding difficulty 24 (70.6%), lethargy 18 (52.9%) and irritability 15 (44.1%). Clinically, pallor 30 (88.2%), tachycardia 29 (85.3%), tachypnea 24 (70.6%), hepatosplenomegaly 30 (88.2%) and eschar 6 (17.6%) were detected. Significant laboratory parameters were anemia 33 (97.1%), leukocytosis 33 (97.1%), thrombocytopenia 17 (50%) and transaminitis 21 (63.6%). Pneumonia 18 (52.9%) was noticed as the major complication. Infants requiring intensive care 17(50%) had characteristic thrombocytopenia, hypoalbuminemia and transaminitis (P<0.05). They recovered well with doxycycline. CONCLUSIONS: Manifestation of scrub typhus in infants tends to be severe with combination of hematologic, pulmonary and hepatic involvement requiring intensive care. The response to doxycycline is good.

Scrub typhus with secondary hemophagocytic lymphohistiocytosis in a 3-month-old child from a tertiary care hospital of Odisha.

Scrub typhus is one of the re-emerging infectious diseases in India, whereas hemophagocytic lymphohistiocytosis (HLH) results from an uncontrolled and ineffective hyperinflammatory response to a variety of triggers. HLH is categorized into primary and secondary type with infection being one of the leading causes of secondary HLH. Here, we report a case of 3-month-old girl diagnosed with scrub typhus associated with secondary HLH as both the age of presentation and the association are rarely reported in literature.

Clinical and Laboratory Profile of Enteric Fever in Children From a Tertiary Care Centre in Odisha, Eastern India.

BACKGROUND: Enteric fever is a major health problem in developing countries. Varied clinical presentation leads to diagnostic dilemmas resulting in fatal complications. OBJECTIVE:  To determine the socio-demographic, clinical manifestations, complications, antibiotic sensitivity pattern, treatment, and outcome in hospitalized enteric fever patients. METHODS: A retrospective case record analysis of hospitalized patients in the age group one to 14 years with a discharge diagnosis of enteric fever was done in a tertiary care centre of Odisha over a period of three years (January 2017 to December 2019). RESULTS: Of 112 patients, 75% of children belonged to the six to 14 years age group with a mean age of 7.6 +/- 3.6 years and a male to female ratio of 1.66:1. The peak of cases was seen during the month of January to June with 94% of cases occurring in low and middle socioeconomic status. The commonest presentation was fever in 98.21%; other features were vomiting (39.29%), pain in abdomen (21.43%), diarrhoea (26.79%), and anorexia (14.29%). Eosinopenia was found in 58.93%, transaminitis in 30.36%, and raised CRP in 73.21%. In 30 children blood culture was positive with sensitivity to third-generation cephalosporin. All isolates were nalidixic acid-resistant Salmonella Typhi (NARST). Complications were seen in 21.42%. All recovered and two left against medical advice. CONCLUSION: Enteric fever is a major threat in the paediatric age group. Early clinical diagnosis with rational use of antibiotics according to sensitivity pattern is important. Improved hygiene, vaccination, and awareness among people is necessary for prevention.

Green synthesis of copper nanoparticles from an extract of Jatropha curcas leaves: characterization, optical properties, CT-DNA binding and photocatalytic activity.

The green synthesis of copper nanoparticles (CuNPs) using a leaf extract from Jatropha curcas (JC) has been documented in our present research work. The existence of flavonoids, tannins, glycosides, and alkaloids was confirmed by the phytochemical analysis of the plant extract and these chemicals can be used as reducing, stabilizing and capping agents. After six months, the JC-CuNPs were found to be stable without any evidence of agglomeration. The JC-CuNPs were characterised by XRD, FT-IR, SEM, TEM and UV-vis spectrophotometry. The average particle and crystal sizes of the JC-CuNPs were found to be 10 ± 1 and 12 ± 1 nm, respectively. The SPR peaks were found at 266 and 337 nm, measured using electronic spectroscopy, and the calculated optical band gap was found to be 3.6 eV at 337 nm, indicating the semiconductor behaviour of the JC-CuNPs. JC-CuNPs have potential photocatalytic activity against methylene blue (MB) compared with other dyes in the presence of sunlight and the rate constant (k) value is 2.30 × 10-4 s-1. The JC-CuNPs also have a binding property with CT-DNA through an intercalation mode and the binding constant (K b) is 1.024 × 102 M-1.

The Dilemma of Diagnosing Hemophagocytic Lymphohistiocytosis in Sickle Cell Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder due to uncontrolled activation of macrophage and cytokine release, which can be due to either genetic causes (familial) or secondary to infections malignancy and other less common cause. Parvovirus B19 rarely causes HLH. Diagnosing HLH in sickle cell disease, which inherently has high ferritin levels and pancytopenia, is particularly challenging. We are reporting HLH as a complication with parvovirus B19 infection in the background of sickle beta-thalassemia. Based on our search of available medical literature, this is the first case of HLH complicating parvovirus B19 infection in a pediatric age group with sickle beta-thalassemia.