A novel generalized fuzzy intelligence-based ant lion optimization for internet of things based disease prediction and diagnosis.

In the modern healthcare system, the function of the Internet of Things (IoT) and the data mining methods with cloud computing plays an essential role in controlling a large number of big data for predicting and diagnosing various categories of diseases. However, when the patients suffer from more than one disease, the physician may not identify it properly. Therefore, in this research, the predictive method using the cloud with IoT-based database is proposed for forecasting the diseases that utilized the biosensors to estimate the constraints of patients. In addition, a novel Generalized Fuzzy Intelligence-based Ant Lion Optimization (GFIbALO) classifier along with a regression rule is proposed for predicting the diseases accurately. Initially, the dataset is filtered and feature extracted using the regression rule that data is processed on the proposed GFIbALO approach for classifying diseases. Moreover, suppose the patient has been affected by any diseases, in that case, the warning signal will be alerted to the patients via text or any other way, and the patients can get advice from doctors or any other medical support. The implementation of the proposed GFIbALO classifier is done with the use of the MATLAB tool. Subsequently, the results from the presented model are compared with state of the art techniques, and it shows that the presented method is more beneficial in diagnosis and disease forecast.

HPVomics: An integrated resource for the human papillomavirus epitome and therapeutics.

Human papillomaviruses (HPVs) belongs to the Papillomaviridae family, which is divided into high-risk (HR), and low-risk (LR) HPVs based on their disease-causing competence. HR-HPVs 16 and 18 are known to cause distinct carcinomas like cervical and head and neck, whereas LR-HPVs are commonly associated with the genital warts. We have developed an integrative platform; HPVomics dedicated to the potential therapeutic regimens targeting all HPV genes including oncoproteins E6, E7 and E5. We primarily focused on eighteen HR-HPVs and eleven LR-HPVs. It mainly deals with therapeutically imperative elements, i.e., vaccine epitopes, siRNAs, sgRNAs, and anti-viral peptides. Simultaneously, it also comprises of genome browser, whole-genome sequences and annotation of HPVs with searching and filtering capabilities. Moreover, we have also developed an integrated support vector machine (SVM) based computational algorithm "HPVepi" for the prediction of HPV epitome. We hope that HPVomics (http://bioinfo.imtech.res.in/manojk/hpvomics/) will assist the scientific community engaged in HPV research.

A novel mechanism of RyeA/SraC induction under acid stress.

RyeA/SraC is a cis-encoded small RNA (sRNA), which act as an anti-toxin to RpoS-regulated RyeB toxin in Escherichia coli. Ectopic expression of RyeA was reported to diminish the RyeB accumulation by serving as a RNA trap. Lower abundance of RyeA in the early exponential growth phase turned out to be the outcome of its degradation by RNase BN/Z. In the current study, we show that RyeA is an acid stress inducible sRNA, and global stress responsive factor RpoS appeared to be inessential in RyeA induction. Although, ryeB-pphA dicistronic transcript at low pH condition was stimulated by ∼4-fold, however, RyeB population was found to be decreased by > 50% under the same condition by the decoy action of enhanced RyeA accumulation. Investigation of the mechanism of RyeA induceduction at low pH in the exponential phase, revealed that RNase BN/Z, which catabolizes RyeA in the exponential phase, appeared to be highly sensitive to low pH stress. Both mRNA and protein level of RNase BN transpired to be decreased to <10% of their initial population. The expression of RyeA under acid stress is regulated by a feed-forward mechanism to normalize the RyeB profusion.

Regulation of RyeA/SraC expression in Escherichia coli.

Small RNAs (sRNAs) play a central role in regulating almost all physiological processes in bacteria. Majority of those sRNAs base pair with their targets and modulate their expressions. RyeA, previously known as SraC in Escherichia coli, is transcribed from a DNA strand complementary to the one from which another stationary phase induced sRNA RyeB/SdsR is synthesised. RyeA and RyeB in the stationary phase constitute a toxin-antitoxin system where RyeA normalizes accumulation of RyeB toxin by acting as RNA sponge. Aside from that, no more information is known about the regulation of RyeA expression. In the current study, we have systematically investigated the regulation of RyeA expression in different growth phases, and identified that RyeA expression is regulated neither by stationary phase-specific σ-factor nor by RNA chaperon Hfq. A dual function ribonuclease RNase BN mitigate its expression in the exponential phase. Thus, deletion of rbn gene promoted the stability of RyeA in the exponential phase. Conversely, RyeB in the stationary phase act as RNA decoy leading to RyeA degradation, and consequently, the preclusion of RyeB in the E. coli genome elevated RyeA. These regulatory mechanisms will help identify the primary role of RyeA in E. coli.

SMEpred workbench: A web server for predicting efficacy of chemicallymodified siRNAs.

Chemical modifications have been extensively exploited to circumvent shortcomings in therapeutic applications of small interfering RNAs (siRNAs). However, experimental designing and testing of these siRNAs or chemically modified siRNAs (cm-siRNAs) involves enormous resources. Therefore, in-silico intervention in designing cm-siRNAs would be of utmost importance. We developed SMEpred workbench to predict the efficacy of normal siRNAs as well as cm-siRNAs using 3031 heterogeneous cm-siRNA sequences from siRNAmod database. These include 30 frequently used chemical modifications on different positions of either siRNA strand. Support Vector Machine (SVM) was employed to develop predictive models utilizing various sequence features namely mono-, di-nucleotide composition, binary pattern and their hybrids. We achieved highest Pearson Correlation Coefficient (PCC) of 0.80 during 10-fold cross validation and similar PCC value in independent validation. We have provided the algorithm in the 'SMEpred' pipeline to predict the normal siRNAs from the gene or mRNA sequence. For multiple modifications, we have assembled 'MultiModGen' module to design multiple modifications and further process them to evaluate their predicted efficacies. SMEpred webserver will be useful to scientific community engaged in use of RNAi-based technology as well as for therapeutic development. Web server is available for public use at following URL address: http://bioinfo.imtech.res.in/manojk/smepred .

Genotoxicity of refinery waste assessed by some DNA damage tests.

Refinery waste effluent is well known to contain polycyclic aromatic hydrocarbons, phenols and heavy metals as potentially genotoxic substances. The aim of the present study was to assess the genotoxic potential of Mathura refinery wastewater (MRWW) by various in vitro tests including the single cell gel electrophoresis, plasmid nicking assay and S1 nuclease assay. Treatment of human lymphocytes to different MRWW concentrations (0.15×, 0.3×, 0.5× and 0.78×) caused the formation of comets of which the mean tail lengths increased proportionately and differed significantly from those of unexposed controls. The toxic effect of MRWW on DNA was also studied by plasmid nicking assay and S1 nuclease assay. Strand breaks formation in the MRWW treated pBR322 plasmid confirmed its genotoxic effect. Moreover, a dose dependent increase in cleavage of calf thymus DNA in S1 nuclease assay was also suggestive of the DNA damaging potential of MRWW. A higher level of ROS generation in the test water sample was recorded which might be contributing to its genotoxicity. Interaction between the constituents of MRWW and calf thymus DNA was also ascertained by UV-visible spectroscopy.

Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD. Objective: To investigate the potential therapeutic benefit of sildenafil on AD. Methods: We performed real-world patient data analysis using the MarketScan® Medicare Supplemental and the Clinformatics® databases. We conducted propensity score-stratified analyses after adjusting confounding factors (i.e., sex, age, race, and comorbidities). We used both familial and sporadic AD patient induced pluripotent stem cells (iPSC) derived neurons to evaluate the sildenafil's mechanism-of-action. Results: We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced incidence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32- 0.66) and a 30% reduced prevalence of AD in Clinformatics® (HR = 0.70, 95% CI 0.49- 1.00) compared to spironolactone. We found that sildenafil treatment reduced tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient iPSC-derived neurons. RNA-sequencing data analysis of sildenafil-treated AD patient iPSC-derived neurons reveals that sildenafil specifically target AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD. Conclusions: These real-world patient data validation and mechanistic observations from patient iPSC-derived neurons further suggested that sildenafil is a potential repurposable drug for AD. Yet, randomized clinical trials are warranted to validate the causal treatment effects of sildenafil in AD.

Intractable diarrhoea caused by cytomegalovirus enterocolitis in an immunocompetent term neonate.

Symptomatic cytomegalovirus (CMV) infection mainly affects preterm and immunocompromised infants and usually manifest as rash, pneumonia, hepatospleenomegaly or encephalitis. To our knowledge intractable diarrhoea at two weeks of age caused by postnatally acquired CMV in immunocompetent term neonate is not reported. An unusual case of postnatally acquired CMV enterocolitis manifesting as protracted diarrhoea in an immunocompetent baby in neonatal period is reported. We conclude that CMV should be considered in the differential diagnosis of intractable diarrhoea in neonatal period and treatment with intravenous ganciclovir for CMV enterocolitis is not only indicated but is therapeutic.

Effect of refinery waste effluent on tocopherol, carotenoid, phenolics and other antioxidants content in Allium cepa.

Pollution in water used for irrigation is a major cause of stress generation in plant system. Under these stress conditions, reactive oxygen species derived from molecular oxygen can accumulate in plant, resulting in the oxidation of nucleic acids, lipids, chlorophyll and so on. This study was conducted in Allium cepa to analyze the alteration in the levels of nonenzymatic antioxidants as a consequence of Mathura refinery waste water (MRWW) exposure. The studied antioxidants were glutathione (GSH) and ascorbic acid (ASC). Their determination was carried out in A. cepa bulbs exposed to different concentrations of MRWW that is 0.25×, 0.5×, 0.75× and 1.0×. A significant increase in the levels of these nonenzymatic antioxidants in onion bulbs upon treatment with MRWW suggested that these can serve as suitable biomarkers of toxicity. The toxicity of waste water was also tested on the level of tocopherol (Toc) and carotenoid (CAR) in onion bulbs, and in both the cases a high level of these metabolites was noticed. Phenolic content of A. cepa after the waste water insult was found to be increased, again a manifestation of adaptation against heavy metal and oxidative stress. It is clear from our findings that GSH, ASC, Toc and CAR in A. cepa system could serve as potential biomarkers for the presence of toxicants like heavy metals and its hazards in MRWW. The test waste water demonstrated profound effects on these parameters which is suggestive of the warrior strategies adopted by the plant system against the pollution-induced stress.

An integrative approach toward identification and analysis of therapeutic targets involved in HPV pathogenesis with a focus on carcinomas.

BACKGROUND: Persistent infection of high-risk HPVs is known to cause diverse carcinomas, mainly cervical, oropharyngeal, penile, etc. However, efficient treatment is still lacking. OBJECTIVE: Identify and analyze potential therapeutic targets involved in HPV oncogenesis and repurposing drug candidates. METHODS: Integrative analyses were performed on the compendium of 1887 HPV infection-associated or integration-driven disrupted genes cataloged from the Open Targets Platform and HPVbase resource. Potential target genes are prioritized using STRING, Cytoscape, cytoHubba, and MCODE. Gene ontology and KEGG pathway enrichment analysis are performed. Further, TCGA cancer genomic data of CESC and HNSCC is analyzed. Moreover, regulatory networks are also deduced by employing NetworkAnalyst. RESULTS: We have implemented a unique approach for identifying and prioritizing druggable targets and repurposing drug candidates against HPV oncogenesis. Overall, hundred key genes with 44 core targets were prioritized with transcription factors (TFs) and microRNAs (miRNAs) regulators pertinent to HPV pathogenesis. Genomic alteration profiling further substantiated our findings. Among identified druggable targets, TP53, NOTCH1, PIK3CA, EP300, CREBBP, EGFR, ERBB2, PTEN, and FN1 are frequently mutated in CESC and HNSCC. Furthermore, PIK3CA, CCND1, RFC4, KAT5, MYC, PTK2, EGFR, and ERBB2 show significant copy number gain, and FN1, CHEK1, CUL1, EZH2, NRAS, and H2AFX was marked for the substantial copy number loss in both carcinomas. Likewise, under-explored relevant regulators, i.e., TFs (HINFP, ARID3A, NFATC2, NKX3-2, EN1) and miRNAs (has-mir-98-5p, has-mir-24-3p, has-mir-192-5p, has-mir-519d-3p) is also identified. CONCLUSIONS: We have identified potential therapeutic targets, transcriptional and post-transcriptional regulators to explicate HPV pathogenesis as well as potential repurposing drug candidates. This study would aid in biomarker and drug discovery against HPV-mediated carcinoma.

Toxicity of boron nitride nanoparticles influencing bio-physicochemical responses in freshwater green algae.

Boron nanoparticles have emerged as promising nanomaterials with a wide array of applications in the biomedical, industrial, and environmental fields. However, the potential impact of these nanoparticles on aquatic organisms is not yet known. In the present study, the comparative impact of boron nitride nanoparticles and its bulk form is investigated on two freshwater algae. For this purpose, the effect on the physiological index, cellular morphology, and biochemistry profiles are examined. In Chlorella vulgaris, nano form of boron nitride is found to reduce the growth more (40%) than its bulk form (with ~ 25% growth reduction) at 50 mgl-1 treatment level. While in case of Coelastrella terrestris, 40% reduction under nano form and 33.33% reduction under bulk form is observed at 100 mgl-1 of boron nitride. Chlorophyll and carotenoid levels were also reduced under nanoparticles compared to the bulk. Proline, lactate dehydrogenase, and malondialdehyde assay were found significantly high under nanoparticle exposure. Additionally, increased catalase and superoxide dismutase enzyme activity under nanoparticle exposure revealed that the antioxidant system was activated in both the algae to eliminate the adverse influence of reactive oxygen species. The shading effect and aggregation of nanoparticles over the surface of algal cells are also important factors in attributing toxicity which are confirmed through the compound, TEM, and SEM micrographs. The study suggests that the nano form is more toxic than the bulk form and toxicity is concentration-dependent.

Causes of Pre-hospital Delay in Acute Stroke in Punjab.

Background Pre-hospital delay, which refers to the time delay between the development of symptoms in the patient and the start of treatment, is one of the major factors impacting the treatment of stroke. This study aimed to identify patient characteristics and factors causing a pre-hospital delay in acute stroke (both ischemic and hemorrhagic) cases. Methodology This prospective follow-up study included 100 patients who presented with clinical features of acute stroke within 48 hours of symptom onset. A pre-designed questionnaire was administered within 72 hours of hospital admission to every patient. Results The mean time to hospital presentation was 7.73 hours. Only 2% of patients were thrombolysed. Age group, gender, education status, occupation, and socioeconomic status were not significantly (p > 0.05) associated with the mean symptom onset time to hospital arrival. Rural area (p < 0.001), nuclear family (p = 0.004), distance from the tertiary care center (p < 0.001), being alone at the time of symptom onset (p < 0.001), lack of knowledge about symptoms of stroke in patient/attendant (p < 0.001), and mode of transport were the factors that emerged as significant predictors of pre-hospital delay on univariate analysis. Living in a nuclear family, distance from the tertiary care center, and mode of transport were the factors that emerged as independent predictors of pre-hospital delay on multiple linear regression analysis. Conclusions In this study, factors associated with delayed hospital presentation including living in a nuclear family, distance from the tertiary care center, and use of public transport to reach the hospital emerged as independent predictors of pre-hospital delay.

Dentofacial manifestations in a child with Jalili syndrome.

Jalili syndrome (JS) (MIM#217080) is a rare autosomal recessive disorder with oculo-dental malformations. The clinical phenotype is characterized by the presence of Cone-Rod Dystrophy (CRD) and Amelogenesis Imperfecta (AI). Genetic mechanism entails a mutation in the CNNM4, a metal transporter gene located on Chromosome 2q11.2. A high fluoride concentration in groundwater has also been identified as an epigenetic factor in this syndrome. JS draws the attention of dentists due to its distinct oral manifestations. To the best of our knowledge, this is the first genetically confirmed pediatric case report from the Indian subcontinent emphasizing the clinical and radiographic features of this condition and its management in a 6-year-old child.

Toxicity evaluation of iron oxide nanoparticles to freshwater cyanobacteria Nostoc ellipsosporum.

The extensive usage of iron oxide nanoparticles (FeO NPs) in commercial and biomedical applications raises the risk of releasing their remains into the aquatic ecosystems and this could possibly cause cytotoxic effects on aquatic organisms. Thus, the toxicity assessment of FeO NPs on cyanobacteria, which are primary producers at the bottom of food chain in aquatic ecosystems, is essential to gain information about the potential ecotoxicological threat on aquatic biota. The present study investigated the cytotoxic effects of FeO NPs on Nostoc ellipsosporum using different concentrations (0, 10, 25, 50 and 100 mg L-1) to track the time-dependent and dose-dependent effects and compared with its bulk equivalent. In addition, the impacts of FeO NPs and bulk counterpart on cyanobacterial cells were assessed under nitrogen as well as nitrogen-deficient conditions, because of ecological role of cyanobacteria in nitrogen fixation. The study revealed that the highest protein content was observed in the control in both types of BG-11 media compared to treatments of nano and bulk particles of Fe2O3. A 23% reduction in protein in nanoparticle treatment and a 14% reduction in bulk treatment at 100 mg L-1 was observed in BG-11 medium. At same concentration, in BG-110 media, this decline was even more intense with 54% reduction in nanoparticle and a 26% reduction in bulk. Catalytic activity of catalase and superoxide dismutase was found to be linearly correlated with the dose concentration for nano and bulk form in BG-11 as well as BG-110 media. The increased levels of lactate dehydrogenase act as biomarker of the cytotoxicity brought on by nanoparticles. Optical, scanning electron, and transmission electron microscopy all demonstrated the cell entrapment, nanoparticle deposition on the cell surface, cell wall collapse and membrane degradation. A cause for concern is that nanoform was found to be more hazardous than bulk form.

Benchmarking and Assessment of Eight De Novo Genome Assemblers on Viral Next-Generation Sequencing Data, Including the SARS-CoV-2.

Viral genomics has become crucial in clinical diagnostics and ecology, not to mention to stem the COVID-19 pandemic. Whole-genome sequencing (WGS) is pivotal in gaining an improved understanding of viral evolution, genomic epidemiology, infectious outbreaks, pathobiology, clinical management, and vaccine development. Genome assembly is one of the crucial steps in WGS data analyses. A series of different assemblers has been developed with the advent of high-throughput next-generation sequencing (NGS). Various studies have reported the evaluation of these assembly tools on distinct datasets; however, these lack data from viral origin. In this study, we performed a comparative evaluation and benchmarking of eight de novo assemblers: SOAPdenovo, Velvet, assembly by short sequences (ABySS), iterative De Bruijn graph assembler (IDBA), SPAdes, Edena, iterative virus assembler, and VICUNA on the viral NGS data from distinct Illumina (GAIIx, Hiseq, Miseq, and Nextseq) platforms. WGS data of diverse viruses, that is, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), dengue virus 3, human immunodeficiency virus 1, hepatitis B virus, human herpesvirus 8, human papillomavirus 16, rhinovirus A, and West Nile virus, were utilized to assess these assemblers. Performance metrics such as genome fraction recovery, assembly lengths, NG50, N50, contig length, contig numbers, mismatches, and misassemblies were analyzed. Overall, three assemblers, that is, SPAdes, IDBA, and ABySS, performed consistently well, including for genome assembly of SARS-CoV-2. These assembly methods should be considered and recommended for future studies of viruses. The study also suggests that implementing two or more assembly approaches should be considered in viral NGS studies, especially in clinical settings. Taken together, the benchmarking of eight de novo genome assemblers reported in this study can inform future public health and ecology research concerning the viruses, the COVID-19 pandemic, and viral outbreaks.

PhoP induces RyjB expression under acid stress in Escherichia coli.

Bacterial small RNAs (sRNAs) play a pivotal role in post-transcriptional regulation of gene expression and participate in many physiological circuits. An ~80-nt-long RyjB was earlier identified as a novel sRNA, which appeared to be accumulated in all phases of growth in Escherichia coli. We have taken a comprehensive approach in the current study to understand the regulation of ryjB expression under normal and pH stress conditions. RpoS was not necessary for ryjB expression neither at normal condition nor under acid stress. Hfq also emerged to be unnecessary for RyjB accumulation. Interestingly, RyjB was detected as a novel acid stress induced sRNA. A DNA binding protein PhoP, a component of PhoP/Q regulon, was found to regulate ryjB expression at low pH, as the elimination of phoP allele in the chromosome exhibited a basal level of RyjB expression under acid stress. Ectopic expression of PhoP in ΔphoP cells restored the overabundance of RyjB in the cell. Overexpression of RyjB increased the abundance of sgcA transcripts, with which RyjB shares a 4-nt overlap. The current study increases our knowledge substantially regarding the regulation of ryjB expression in E. coli cell.

A Meta-analysis of Complication Rates Among Various Surgical Modifications of Pectoralis Major Myocutaneous Flap.

The purpose of this study is to aggregate and summarize the complication rates among various modified techniques of pectoralis major myocutaneous flap harvesting. Various databases were searched from its inception to September 2020. Studies describing surgical management of head and neck oncologic reconstruction using pectoralis major myocutaneous flap and its surgical modifications were included in study. All included studies: (1) described a pectoralis major flap harvesting technique categorized by author as conventional technique, bipaddle or bilobed flap, segmental flap, flap transfer using subclavicular route, skin paddle over Pectoralis Major, Flap with Multiple vascular supply, U shaped skin paddle, modified short incision technique; and (2) reported the number of postoperative complications in participants. Meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total 183 studies were included. Segmental flap (0.20%), flap with multiple vascular supply (5.18%) and parasternal skin flap (6.38%) had the highest rates of total complications and were the only techniques to show a statistically significant increase in odds ratio compared with conventional technique (odds ratio 1.89, 9.05 and 7.26, respectively, P < 0.05). Bipaddle flap (57.48%) and u shaped skin flap (78.05%) show statistically significant decrease in odds ratio as compared to conventional technique. Among all the modifications in surgical technique of pectoralis major myocutaneous flap harvesting bipaddle flap and u shaped skin flap show least total complication rates. But on the contrary rates of partial flap necrosis and fistula are significantly higher in bipaddle flap as compared to conventional technique. As such, the choice of surgical technique should primarily be made based on the defect size, patient selection and surgeons' discretion rather than the presumed complication rate.

Evaluation of biphasic hydroxapatite and ß-tricalcium phosphate as a bone graft material in the treatment of periodontal vertical bony defects - A clinical and digital radiological measurement study.

Aims and Objective: The present study aimed to evaluate 2 bone graft materials, that is, biphasic hydroxyapatite and ß-tricalcium phosphate, in the treatment of periodontal vertical bony defects. In term of attachment level, probing depth and radiographic bone level changes. Also, a new digital method of radiographic assessment was used for measurement of vertical bone defect. Material and Methods: Ten subjects with periodontitis and having two or more vertical bony defects were enrolled in the study. Patients were classified randomly into 2 groups. Group I consisted of the experimental site where defect was filled with biphasic hydroxyapatite and ß-tricalcium phosphate graft and Group II consisted of control site where only the open flap debridement (OFD) was carried out. Clinical parameters were evaluated at baseline, 3 and 6 months; Radiographs were taken at baseline and 6 months after surgery. Results: Overall, by the end of 6 months, biphasic hydroxyapatite and ß-tricalcium phosphate and OFD treatment groups exhibited a significant reduction in probing depth almost by 75% and gain in clinical attachment level at follow-up. In the biphasic hydroxyapatite and ß-tricalcium phosphate group, radiographic bone level gain appeared to be greater than in the OFD group. Conclusion: In the present study, biphasic hydroxyapatite and ß-tricalcium phosphate have shown promising results and have showed reduction in probing depth, a resolution of osseous defects and gain in clinical attachment level when compared to open flap debridement.

Role of Hyperbilirubinaemia as a Predictor of Complicated Appendicitis in Paediatric Population.

BACKGROUND: Acute appendicitis is a common surgical emergency amongst the paediatric population. Available diagnostic tools are focussed to make a diagnosis of acute appendicitis. A definitive predictive factor for the diagnosis of complicated appendicitis is lacking. Thus, this aims to analyse hyperbilirubinaemia as a predictor of complicated appendicitis amongst the paediatric population. MATERIALS AND METHODS: A prospective observational study was conducted in a tertiary hospital from November 2018 to October 2019. All children undergoing emergency appendectomy were included in the study. Preoperatively, patients were evaluated clinically, and routine investigations including total and direct serum bilirubin were sent. All patients were grouped as 'simple appendicitis' or 'complicated appendicitis' based on intra-operative and histological findings. Bilirubin level was compared between these groups and analysed. RESULTS: A total of 52 children fulfilling the inclusion criteria were included. The mean age was 13.2 ± 4.2 years, and the male: female ratio was 2.1:1. Thirty-four (65.4%) had simple appendicitis and 18 (34.6%) had complicated appendicitis. Total bilirubin was 23.83 ± 5.94 mmol/L in the complicated appendicitis group and 13.15 ± 3.29 mmol/L in the simple appendicitis group. Direct bilirubin was 5.28 ± 2.22 mmol/L in complicated appendicitis and 2.62 ± 0.83 mmol/L in simple one. Both total and direct bilirubin were significantly high in the complicated group (P < 0.001) compared to the simple appendicitis group. On the Receiver operating curve (ROC), the best cutoff value for total and direct bilirubin was 21 and 5.5 mmol/L, respectively. The sensitivity and specificity of total and direct bilirubin were 72.2%, 100%, and 61.1%, and 85.3%, respectively. CONCLUSION: It is concluded that hyperbilirubinaemia is a good predictor for paediatric complicated appendicitis.

Autoimmune polyendocrine syndrome II presenting paradoxically as Takotsubo cardiomyopathy: a case report and reappraisal of pathophysiology.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is a rare disease entity characterized by acute, non-ischemic, reversible myocardial dysfunction that mimics acute myocardial infarction. Activation and excessive outflow of sympathetic nervous system are believed to be central to the figure in the disease pathogenesis. Adrenocortical hormones potentiate the systemic actions of sympathetic nervous system and accordingly are essential for regulation of myocardial function. We present an unusual case of a middle-aged woman with primary adrenal insufficiency who presented paradoxically with TCM. CASE PRESENTATION: A 50-year-old woman with past history of hypothyroidism presented to emergency department with history of acute chest pain and syncope. There was no significant drug history or history of an emotional or physical stimulus prior to admission. Prominent pigmentation over the tongue and skin creases of hands were noted. On presentation, she was in shock and had ventricular tachycardia which required electrical cardioversion. The subsequent electrocardiogram demonstrated diffuse T-wave inversions with prolonged QTC. There was apical hypokinesia on echocardiogram, and cardiac biomarkers were elevated. There was persistent inotropic requirement. She had marked postural symptoms, and a postural blood pressure drop of 50 mm Hg was present. Initial laboratory parameters were significant for hyperkalemia (7.8 mEq/L) and hyponatremia (128 mEq/L). These findings prompted evaluation for adrenal insufficiency which was confirmed with appropriate tests. Autoimmune polyendocrine syndrome II was thus diagnosed based on the above findings. Coronary angiography revealed normal coronaries. The diagnoses of TCM was established in accordance with the International Takotsubo Diagnostic Criteria. She was started on stress dose steroid replacement therapy and improved dramatically. At one month of follow-up, the patient is asymptomatic, and there was normalization of her left ventricular function. CONCLUSIONS: Intricate relationship and interplay exist between the steroid hormones and catecholamines in the pathogenesis of TCM. Steroid hormones not only potentiate the actions of catecholamines, but they also regulate and channelize catecholaminergic actions preventing their deleterious effects on the cardiac tissue. Hence, both steroid deficiency and exogenous steroid replacement may precipitate TCM. Evidence from more such cases and larger perspective studies in future will further improve our understanding of this complex disease process and its myriad associations.