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.

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.

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.

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.

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.

Factors Influencing the Age at Discharge of Very Low Birth Weight Preterm Neonates From a Neonatal Intensive Care Unit in Eastern India: A Cohort Study.

OBJECTIVE: To study factors that influence the age of discharge of very low birth weight (VLBW) preterm neonates from the Neonatal Intensive Care Unit (NICU). SETTING: This cohort study was conducted in the NICU, Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India, from April 2019 to December 2019. PATIENTS: Neonates whose birth weight was <1500 g and gestation <37 weeks were enrolled. Those having major congenital malformation were excluded. OUTCOME: Age at discharge (in days). RESULTS: Out of 114 neonates enrolled, 84 neonates completed the study and discharged, 29 neonates died during the study, and one patient left against medical advice. Demographic, antenatal, neonatal factors, and mother's participation in care of the baby were compared with respect to age at discharge in univariate analysis. Those found significant on univariate analysis were subjected to multivariate analysis. In the multivariate analysis model two independent predictors were observed, birth weight and gestation, which were inversely related to age at discharge. CONCLUSION: Birth weight and gestation are the two most important factors which significantly influence the age at discharge from hospital of VLBW preterm neonates.

Environmental distribution and ecotoxicological concerns of phthalic acid esters in creek ecosystem.

The long-term ecological risk of synthetic organic contaminants, exclusively endocrine disrupting chemicals (EDCs) such as phthalates has threatened reclaimed seawater quality in marine environment. In this study, environmental distributions of 14 phthalic acid esters (PAEs) in seawater, and biota (fish and crab) across Thane Creek, Mumbai India is reported. Identification and quantifications of phthalates in environmental matrices was carried out using GC-MS technique. Abundance of phthalates in each matrix was discussed and compared with literature value. Total phthalate esters concentrations in seawaters, fish and crab samples were found to be 104.8 ± 37.8 µg L-1, 113 ± 36.4 µg g-1 and 155 ± 38 µg g-1 (dry weight) respectively. Di-n-butylphthalate (DBP) was most abundant compound among analyzed PAEs in all tested aquatic media. In situ bio-concentration factors (BCFs) were calculated for all monitored phthalates in fish and crabs and compared with log Kow values. Risk quotient and estradiol equivalent concentration were also calculated to evaluate ecological risk and estrogenic potential of seawater in terms of DBP and di (2-ethylhexyl) phthalate. The average values of total PAEs daily intake were calculated as 58.1 ± 13.6 and 79.6 ± 19.6 (µg kg-1-bw/day) for fish and crab respectively in an adult population.

Polybrominated diphenyl ethers (PBDEs) in core sediments from creek ecosystem: occurrence, geochronology, and source contribution.

The levels of 15 polybrominated diphenyl ether (PBDE) congeners in grab sediment and sediment cores from the Thane creek were monitored for their spatial and temporal distribution. Total PBDE (ΣPBDE) concentrations in grab sediments were ranging from 15.98 to 132.72 ng g-1 dry weight. BDE-209 was the most abundant congener with percentage contribution in the range of 19-35% to total PBDEs. Total PBDE show multimode concentration with depth in sediment, among which mode at a depth of 10 cm is predominant. Results of sediment core also indicates PBDEs were enormously used in last two decades in surrounding area. Sedimentation rate at the creek was also evaluated using Pb210 dating technique. Average percentage contribution of commercial penta-BDE (fP), octa-BDE (fO), and deca-BDE (fD) to the profile found in sediments collected across Thane creek were 24 ± 5, 5 ± 1 and 69 ± 7% (p < 0.001) respectively. Levels of all measured PBDEs in sediment met with guideline values except for the penta-BDE (total, BDE-99 and BDE-100) at few locations.

Distribution and ecotoxicological concerns of persistent organic pollutants in sediment from creek ecosystem.

In order to study the distribution and ecotoxicological concerns of persistent organic pollutants, grab sediment samples were collected from different locations across Thane creek, India. Analyses of samples were carried out using gas chromatography (GC)-electron capture detector and GC-mass spectrometry techniques. In organochlorine pesticides (OCPs), DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl) ethane), DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene), DDD (1-chloro-4-(2,2-dichloro-1-(4-chlorophenyl)ethyl) benzene) and α, ß, and γ conformer of hexachlorocyclohexane (HCH), and 9 polychlorinated biphenyls (PCBs) congeners were analyzed in surface sediment samples. Concentrations of these pollutants in grab sediment samples may indicate their current use and impact on marine ecosystem. Average concentrations of total DDT (including DDD and DDE), HCH, and Σ9PCBs were found to be 4.9, 12.5, and 2.9 µg kg(-1)(dry weight) respectively. High concentrations of OCPs and PCBs were found at discharge locations in creek compared to other locations. Location-wise distribution of OCPs and PCBs indicates their high concentrations at the waste water receiving point. Data were compared for ecotoxicological impacts based on the levels specified in the sediment quality standards of the US Environmental Protection Agency and the Canadian Council of Ministers of the Environment. γ-HCH was found to have maximum potential to induce ecotoxicological impacts.