Single Center Outcomes of Status Epilepticus at a Paediatric Intensive Care Unit

Background: Status epilepticus (SE) is a frequent admission diagnosis to paediatric intensive care units (PICUs) and is associated with variable outcomes. We have audited our experience of patients presenting in SE at a Canadian PICU to determine unfavorable outcome variables. Methods: Charts of patients \u3c18 years of age presenting in SE to a tertiary care PICU over a 10-year period were audited. Data were analyzed at three care-points: transport, the emergency department (ED) and the PICU. Patient outcome before PICU discharge was categorized as favorable for return to pre-status functioning level or unfavorable for new deficit/death. Student\u27s t-test and the Kruskal-Wallis test were used for analysis of normal and skewed continuous variables, respectively, and either Chi-square test or Fisher\u27s exact test for categorical variables. Results: 189 patients (54% males) were identified with a median age of 1.9 years. Idiopathic SE had the highest incidence; infectious/vascular etiologies were associated with more unfavorable outcomes. Progression to refractory SE in the ED had a higher incidence of death (p\u3c0.05). Patients with an unfavorable outcome had a higher incidence of apnea during transport (p=0.01), longer hospital stays (p\u3c0.05), need for therapeutic coma (p=0.01), longer duration of therapeutic coma (p\u3c0.05), need for mechanical ventilation (p\u3c0.05), and recurrent or refractory seizures during inpatient stay (p\u3c0.05). Multivariate analysis of unfavorable outcomes of patients in SE presenting to the PICU included renal failure, cerebral edema, apnea during transport, refractory seizures, and recurrent seizures. Conclusions: Refractory seizures in children presenting with SE are associated with worsened outcomes in the PICU

Promising selective MAO-B inhibition by sesamin, a lignan from Zanthoxylum flavum stems

© 2020 The Author(s) Monoamine oxidase inhibition is an important therapeutic approach for various neurodegenerative disorders. Reversible MAO inhibitors selectively targeting only one isoform possess substantial merit in terms of safety, efficacy, and side effect profile. This study aimed to isolate the secondary metabolites of Zanthoxylum flavum stems and evaluate their recombinant human MAO inhibition, antimicrobial, and antiprotozoal activities. As a result, fourteen compounds were isolated and identified (nine of them were reported from Z. flavum for the first time). Compound 3 (sesamin) exhibited potent selective MAO-B inhibition (IC50 value of 1.45 ± 0.05 µM) which reported herein for the first time. Compound 2 showed selective MAO-A inhibition activity, compound 5 exhibited good trypanocidal activity, and compound 7 displayed moderate antibacterial activity. The promising MAO-B inhibitory activity of sesamin provoked us to further explore the kinetic properties, the binding mode, and the underlying mechanism of MAO-B inhibition by this lignan. This detailed investigation substantiated a reversible binding and mixed MAO-B catalytic function inhibition via sesamin (Ki: 0.473 ± 0.076 μM). Selectivity and reversibility of sesamin on MAO-B provide exciting prerequisites for further in vivo investigation to confirm its therapeutic potentiality

Seroprevalencija virusnog proljeva goveda u uzgojnim farmama u Indiji

Bovine viral diarrhoea (BVD) is an important infectious viral disease affecting cattle populations all over the world. In addition to direct loss caused by the disease, the virus causes immunosuppression thereby predisposing the host to other diseases. A cross-sectional study was undertaken to detect the prevalence of BVD in 14 well-organized herds located in different parts of India. A total of 880 serum samples (646 cattle and 234 buffaloes) were screened by a commercial ELISA kit, detecting antibodies towards the p80 (NS3) region of BVDV. The overall true prevalence was 56.67% (95% CI: 53.26-60.02%) and within herds, it ranged from 0-99.99%. The prevalence rate was higher in cattle (65.42%) than in buffaloes (32.49%) and the difference was statistically significant. Further, a significant difference in prevalence among cattle breed types was recorded, with the lowest in indigenous cattle (16.49%) followed by crossbreeds (16,97% and exotic breeds (87.80%). Higher positivity was detected among females (68.87%) than males (48.83%) but this difference was not significant, as revealed by multivariate regression analysis. Of the 10 semen stations studied, the prevalence varied from 9.72% to 72.68%. However, none of the animals from these semen stations turned positive in the antigen ELISA test, suggesting the antibodies detected in this study were from past infections. On the two dairy farms/bull mother farms showing very high positivity, two (one each) persistently infected cows were detected during whole herd screening by antigen ELISA test. One bull mother farm was free of BVD antibodies suggesting it is possible to maintain BVDV-free herds. The present study indicates the endemicity of BVDV in Indian organized herds, and therefore a suitable testing strategy and management should be adopted in response to testing to control the introduction and further transmission of the disease on farms.Virusni proljev goveda (BVD) važna je zarazna virusna bolest od koje obolijevaju goveda diljem svijeta. Osim izravnoga gubitka uzrokovanog bolešću, virus uzrokuje imunosupresiju zbog čega domaćin postaje podložan drugim bolestima. Provedeno je presječno istraživanje kako bi se otkrila prevalencija BVD-a u 14 organiziranih uzgoja koji su uključivali farme bikovskih majki i stanice za proizvodnju sjemena za UO. Uzgoji su se nalazili u različitim područjima Indije. Ukupno je 880 uzoraka seruma (646 goveda i 234 bivola) analizirano komercijalnim ELISA testom za otkrivanje protutijela na regiju p80 (NS3) BVDV-a. Ukupna je stvarna prevalencija iznosila 56,67 % (95 % CI: 53,26 – 60,02 %), a unutar stada kretala se u rasponu od 0 do 99,99 %. Stopa prevalencije bila je veća u goveda (65,42 %) nego u bivola (32,49 %) i razlika je bila statistički znakovita. Nadalje, zabilježena je znakovita razlika u prevalenciji među pasminama goveda, s tim da je najmanja bila u autohtonih pasmina goveda (16,49 %), slijede zatim križanci (61,97 %) te egzotične pasmine (87,80 %). Veća je pozitivnost zabilježena u ženki (68,87 %) u odnosu na mužjake (48,83 %), ali multivarijantna regresijska analiza nije potvrdila znakovitost te razlike. Među deset istraživanih stanica za proizvodnju sjemena za UO, prevalencija je varirala od 9,72 % do 72,68 %. No ni jedna životinja iz tih stanica nije bila pozitivna na antigenskom ELISA testu, što pokazuje da protutijela pronađena u ovom istraživanju potječu od prijašnjih infekcija. Na dvjema farmama mliječnih krava - bikovskih majki tijekom testiranja cijelog stada antigenskim ELISA testom, utvrđena je visoka pozitivnost pri čemu su dvije krave bile stalno zaražene. Na jednoj farmi bikovskih majki nisu pronađena BVD protutijela što upućuje na to da je moguće održati stada bez ove bolesti. Rezultati istraživanja upućuje na endemičnost BVDV-a u organiziranim uzgojima goveda u Indiji zbog čega postoji potreba za odgovarajućim strategijama testiranja i upravljanja stadom kako bi se kontrolirao unos bolesti i njezino širenje na farmama

Outcome of gastrointestinal surgery during COVID-19 lockdown in a tertiary care hospital, Nepal

Introduction: Perioperative strategies have been changing due to the COVID-19 pandemic to prevent the risk of postoperative complications and transmission of infection. This study was aimed to assess the outcome of gastrointestinal surgery and the risk of transmission by implementing COVID-19 testing criteria and surgical strategy. Method: This was a retrospective descriptive study conducted at the department of surgery at Patan Hospital, Nepal, during COVID-19 lock-down from 24 march to 15 June 2020. All patients who underwent gastrointestinal (GI) surgery were included. High-risk patients (as defined by the Hospital Incident Command System, HICS) were tested for COVID-19 preoperatively. Surgery was performed in COVID operating room with full protective gear. Low-risk patients were not tested for COVID-19 preoperatively and performed surgery in non-COVID OR. Data from patient’s case-sheets were analyzed descriptively for age, gender, comorbidities, hospital stay, RT-PCR results, surgeries, and postoperative complications. Result: There were total 44 GI surgeries performed; 31(70.5%) were emergency, 5(11.3%) semi-emergency and 8(18.2%) oncology. There were 11(25%) patients tested for COVID-19 preoperatively and were negative. Nine HCWs tested for COVID-19 randomly were negative. Severe postoperative complications developed in 3 patients, with one mortality. Conclusion: Among GI surgeries, there was no increase in postoperative complications and transmission of COVID-19 to the patients or HCWs following the implementation of standard testing criteria and surgical strategy

Isolation and Biological Evaluation of Prenylated Flavonoids from Maclura pomifera

Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds (I–IV) along with eleven known compounds (V–XV). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with δ and μ opioid receptors (−49.7 and −53.8% displacement, resp.). Compound I was found to be possibly allosteric for κ and μ opioid receptors (−88.4 and −27.2% displacement, resp.) and showed moderate activity (60.5% displacement) towards CB1 receptor. Compound II exhibited moderate activity towards cannabinoid receptors CB1 and CB2 (47.9 and 42.3% displacement, resp.). The known compounds (V–VIII) exhibited prominent activity towards cannabinoid receptors: pomiferin (V) (IC50 of 2.110 and 1.318 μM for CB1 and CB2, resp.), auriculasin (VI) (IC50 of 8.923 μM for CB1), warangalone (VII) (IC50 of 1.670 and 4.438 μM for CB1 and CB2, resp.), and osajin (VIII) (IC50 of 3.859 and 7.646 μM for CB1 and CB2, resp.). The isolated compounds were also tested for inhibition of human monoamine oxidase-A and monoamine oxidase-B enzymes activities, where all the tested compounds showed fewer inhibitory effects on MAO-A compared to MAO-B activities: auriculasin (VI) (IC50 of 1.91 and 45.98 μM for MAO-B and MAO-A, resp.)

Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre

Background: Phyllodes tumors (PTs) of the breast are rare fibroepithelial tumors that are generally more prone to recurrence.Aims and objectivesThis study aimed to assess the clinicopathological features, diagnostic modalities, and therapeutic interventions, along with their respective outcomes, to identify the factors associated with a recurrence of PTs of the breast.MethodologyA retrospective cohort and observational study was conducted, which entailed analyzing the clinicopathological data of patients who were previously diagnosed or presented with PTs of the breast between 1996 and 2021. Data included the total number of patients diagnosed with PTs of the breast and their ages, tumor grade on initial biopsy, tumor location (left or right breast), tumor size, therapeutic interventions carried out (including surgery-either mastectomy or lumpectomy-and adjuvant radiotherapy), final tumor grade, recurrence status, type of recurrence, and time to recurrence.ResultsWe analyzed data on a total of 87 patients who were pathologically proven to have PTs, and 46 patients (52.87%) were found to have recurrences. All patients were female, with a mean age at diagnosis of 39 years (range 15-70). Patients aged 40 years, with a rate of recurrence of 45.65% (n = 21/46). A total of 55.4% of patients presented with primary PTs and 44.6% had recurrent PTs at presentation. The average time to local recurrence (LR) from the completion of treatment was 13.8 months, whereas for systemic recurrence (SR), it was 15.29 months. Surgery (mastectomy/lumpectomy) was the major determinant for local recurrence (p ConclusionPatients who received adjuvant radiotherapy (RT) had a minimal recurrence of PTs. Patients who were found to have a malignant biopsy on initial diagnosis (triple assessment) had a higher incidence of PTs and were more prone to SR than LR. Surgery was a determining factor in the increased rate of LR, with lumpectomy associated with a higher incidence of LR than mastectomy

An electronic application for rapidly calculating Charlson comorbidity score

BACKGROUND: Uncertainty regarding comorbid illness, and ability to tolerate aggressive therapy has led to minimal enrollment of elderly cancer patients into clinical trials and often substandard treatment. Increasingly, comorbid illness scales have proven useful in identifying subgroups of elderly patients who are more likely to tolerate and benefit from aggressive therapy. Unfortunately, the use of such scales has yet to be widely integrated into either clinical practice or clinical trials research. METHODS: This article reviews evidence for the validity of the Charlson Comorbidity Index (CCI) in oncology and provides a Microsoft Excel (MS Excel) Macro for the rapid and accurate calculation of CCI score. The interaction of comorbidity and malignant disease and the validation of the Charlson Index in oncology are discussed. RESULTS: The CCI score is based on one year mortality data from internal medicine patients admitted to an inpatient setting and is the most widely used comorbidity index in oncology. An MS Excel Macro file was constructed for calculating the CCI score using Microsoft Visual Basic. The Macro is provided for download and dissemination. The CCI has been widely used and validated throughout the oncology literature and has demonstrated utility for most major cancers. The MS Excel CCI Macro provides a rapid method for calculating CCI score with or without age adjustments. The calculator removes difficulty in score calculation as a limitation for integration of the CCI into clinical research. The simple nature of the MS Excel CCI Macro and the CCI itself makes it ideal for integration into emerging electronic medical records systems. CONCLUSIONS: The increasing elderly population and concurrent increase in oncologic disease has made understanding the interaction between age and comorbid illness on life expectancy increasingly important. The MS Excel CCI Macro provides a means of increasing the use of the CCI scale in clinical research with the ultimate goal of improving determination of optimal treatments for elderly cancer patients

ICF, An Immunodeficiency Syndrome: DNA Methyltransferase 3B Involvement, Chromosome Anomalies, and Gene Dysregulation

The immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF) is the only disease known to result from a mutated DNA methyltransferase gene, namely, DNMT3B. Characteristic of this recessive disease are decreases in serum immunoglobulins despite the presence of B cells and, in the juxtacentromeric heterochromatin of chromosomes 1 and 16, chromatin decondensation, distinctive rearrangements, and satellite DNA hypomethylation. Although DNMT3B is involved in specific associations with histone deacetylases, HP1, other DNMTs, chromatin remodelling proteins, condensin, and other nuclear proteins, it is probably the partial loss of catalytic activity that is responsible for the disease. In microarray experiments and real-time RT-PCR assays, we observed significant differences in RNA levels from ICF vs. control lymphoblasts for pro- and anti-apoptotic genes (BCL2L10, CASP1, and PTPN13); nitrous oxide, carbon monoxide, NF-κB, and TNFa signalling pathway genes (PRKCH, GUCY1A3, GUCY1B3, MAPK13; HMOX1, and MAP4K4); and transcription control genes (NR2F2 and SMARCA2). This gene dysregulation could contribute to the immunodeficiency and other symptoms of ICF and might result from the limited losses of DNA methylation although ICF-related promoter hypomethylation was not observed for six of the above examined genes. We propose that hypomethylation of satellite 2at1qh and 16qh might provoke this dysregulation gene expression by trans effects from altered sequestration of transcription factors, changes in nuclear architecture, or expression of noncoding RNAs

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic