Clinical Findings and Pro-Inflammatory Cytokines in Dengue Patients in Western India: A Facility-Based Study

BACKGROUND: Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-gamma, TNF-alpha, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-gamma were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-gamma and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-gamma showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-gamma and IL-8 were positively associated with alanine transaminase levels. CONCLUSIONS/SIGNIFICANCE: Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-gamma and IL-8 levels had greater significance than absolute values in DHF pathogenesis

Medio-Frontal and Anterior Temporal abnormalities in children with attention deficit hyperactivity disorder (ADHD) during an acoustic antisaccade task as revealed by electro-cortical source reconstruction

<p>Abstract</p> <p>Background</p> <p>Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent disorders in children and adolescence. Impulsivity is one of three core symptoms and likely associated with inhibition difficulties. To date the neural correlate of the antisaccade task, a test of response inhibition, has not been studied in children with (or without) ADHD.</p> <p>Methods</p> <p>Antisaccade responses to visual and acoustic cues were examined in nine unmedicated boys with ADHD (mean age 122.44 ± 20.81 months) and 14 healthy control children (mean age 115.64 ± 22.87 months, three girls) while an electroencephalogram (EEG) was recorded. Brain activity before saccade onset was reconstructed using a 23-source-montage.</p> <p>Results</p> <p>When cues were acoustic, children with ADHD had a higher source activity than control children in Medio-Frontal Cortex (MFC) between -230 and -120 ms and in the left-hemispheric Temporal Anterior Cortex (TAC) between -112 and 0 ms before saccade onset, despite both groups performing similarly behaviourally (antisaccades errors and saccade latency). When visual cues were used EEG-activity preceding antisaccades did not differ between groups.</p> <p>Conclusion</p> <p>Children with ADHD exhibit altered functioning of the TAC and MFC during an antisaccade task elicited by acoustic cues. Children with ADHD need more source activation to reach the same behavioural level as control children.</p

Travel restrictions and infectious disease outbreaks

BACKGROUND: A key purpose of the International Health Regulations (IHR) is to prevent unwarranted interruptions to trade and travel during large and/or transnational infectious disease outbreaks. Nevertheless, such outbreaks continue to disrupt the travel industry. This aspect of the IHR has received little attention in the academic literature despite its considerable impact on affected States and commercial activity. This article outlines the challenges and gaps in knowledge regarding the relationship between outbreaks and the travel sector and discusses the opportunities for further research and policy work to overcome these challenges. METHODOLOGY: We conducted a literature review on the relationship between outbreaks and travel restrictions, with a particular focus on the 2014-16 Ebola epidemic in West Africa. This review was complemented by an expert roundtable at Chatham House and further supported by case studies and qualitative interviews. RESULTS: Numerous travel stakeholders are affected by, and affect, large-scale infectious disease outbreaks. These stakeholders react in different ways: peer pressure plays an important role for both governments and the travel sector, and the reactions of the media and public influence and are influenced by these stakeholders. While various data sources on travel are available, and World Health Organization is mandated to work with States, there is no recognized coordinating body to disseminate timely, consistent, reliable and authoritative information and best practices to all stakeholders. CONCLUSION: This article highlights the interdependent relationship between various travel stakeholders. The reasons for interruption of travel during the 2014-16 Ebola outbreak were complex, with decisions by States only partly contributing to the cessation. Decisions by non-state actors, particularly the travel industry itself, contributed significantly and were based on a variety of factors. Further research, analysis and policy development are required to mitigate the health and economic consequences of infectious disease outbreaks. Any further research will also need to take account of COVID-19 travel-related issues

Use of intra-amniotic urea as a second trimester abortifacient

Seventy cases of mid-trimester pregnancies were terminated by using 200 ml. of 40&#x0025; intra-amniotic urea, over a 13 month period from 1st August. 1977 to 31st August, 1978. The success rate was 88.7&#x0025; and the mean induction-abortion interval was 30.7 hours. No major complications were observed

An in vitro study of cytotoxicity of organophosphate insecticides (Imidacloprid, Profenofos, Dichlorvos) and natural products (Neem oil and Dashparni ark) on human peripheral lymphocytes by MTT and Trypan blue assay

It is a well-known fact that the human population of India is increasing very fast. Everybody needs food to survive. Agricultural products must be boosted by adding adequate fertilisers and using appropriate insecticides. Organophosphates are one of the most frequently used insecticides. Their overuse leads to soil contamination by agricultural runoff. The insecticides may enter drinking water as well. Since organophosphates are acetylcholinesterase inhibitors, they can be dangerous for human health if abnormal amounts are present in drinking water or are consumed as residues on fruits and vegetables. Hence, a toxicity study by MTT and Trypan Blue Assay of three common insecticides (Imidacloprid, Profenofos, Dichlorvos) and two natural products (Dashparnik ark and Neem oil) on lymphocytes was taken up. The insecticides were used at concentrations of 1mM, 4mM, 8mM and 12mM. It was found that at 4 hours of incubation at 1mM Imidacloprid showed the greatest drop in viability followed by Dichlorvos and the least harm was caused by Profenofos. The drop was consistent and dose dependent in the case of Profenofos, whereas at a higher concentration the viability generally increased. For 18 hours of incubation, the same trend was observed, but the decrease and increase were more pronounced. In the case of Profenofos and Dichlorvos the viability percent rises above that of the control. It was probably due to the defense mechanism involving the P450 detoxification pathway of the cells, which is activated if they are exposed to a higher concentration of the damaging factors. This is also supported by other workers mentioned in the discussion section of this paper. The damage to the cells, as evident in the fall in viability, was of lesser magnitude when organic insecticides were used. In the case of Neem nano-drop emulsion, a significant fall in viability was noted only at 2mg/ml. However, it is not sprayed as a nano-emulsion because it is not particularly harmful. The fourth insecticide that was taken up for study was Dashparni Ark. In this case, at 5µl/ml of distilled water (obtained by dilution) very little damage was evident, but at higher concentration it boosted the viability. Apparently, the extract of leaves fermented in cow urine and cow dung was less damaging than that of other insecticides. Thus, organic insecticides are safer to use because they are ecofriendly and do not harm non-target organisms. This is written on the basis of MTT assay results

Cytokine levels (pg/ml) in early and late days of illness in DF and DHF patients.

<p>Scatter plot of levels of cytokine (pg/ml) in early (2–5) and late (6–15) days of illness. A) IFN-γ, B) TNF-α, C) IL-6 and D) IL-8. The two panels show DF and DHF cases. The mean levels are indicated with the red line. The cut-off (mean levels in healthy controls+2SD) for each cytokine is shown with a dashed line.</p

Demographics, Serotypes detected and disease categories.

<p>Demographics, Serotypes detected and disease categories.</p

Association of cytokine levels with clinical parameters of dengue patients.

<p>A. Association of levels of IFN-γ with ALT levels. B. Association of levels of IL-8 with ALT levels. C. Tukey box-whisker plot with median, range with the upper and lower quartiles and outliers of IL-8 levels in thrombocytopenic (platelet count <100,000) and non- thrombocytopenic (platelet count >100,000) dengue patients. A & B] Pearson correlation used for analysis, <i>p</i><0.05 considered significant. C] <i>p</i>-value calculated by ANOVA, <i>p</i><0.05 considered significant. Outliers showed as dots and those above the axis limit not shown in graph but included in analysis.</p

Age-wise distribution of DF and DHF cases.

<p>Number of dengue cases plotted according to age – groups.</p

Laboratory findings in DF and DHF.

<p>Cases compared using chi-square test, <i>p</i>- value <0.05 considered significant.</p