Schistosomiasis transmission at high altitude crater lakes in Western Uganda

<p>Abstract</p> <p>Background</p> <p>Contrary to previous reports which indicated no transmission of schistosomiasis at altitude >1,400 m above sea level in Uganda, in this study it has been established that schistosomiasis transmission can take place at an altitude range of 1487–1682 m above sea level in western Uganda.</p> <p>Methods</p> <p>An epidemiological survey of intestinal schistosomiasis was carried out in school children staying around 13 high altitude crater lakes in Western Uganda. Stool samples were collected and then processed with the Kato-Katz technique using 42 mg templates. Thereafter schistosome eggs were counted under a microscope and eggs per gram (epg) of stool calculated. A semi-structured questionnaire was used to obtain demographic data and information on risk factors.</p> <p>Results</p> <p>36.7% of the pupils studied used crater lakes as the main source of domestic water and the crater lakes studied were at altitude ranging from 1487–1682 m above sea level. 84.6% of the crater lakes studied were infective with over 50% of the users infected.</p> <p>The overall prevalence of <it>Schistosoma mansoni </it>infection was 27.8% (103/370) with stool egg load ranging from 24–6048 per gram of stool. 84.3%( 312) had light infections (<100 eggs/gm of stool), 10.8%( 40) had moderate infections (100–400 eggs/gm of stool) and 4.9% (18) had heavy infections (>400 egg/gm of stool). Prevalence was highest in the age group 12–14 years (49.5%) and geometric mean intensity was highest in the age group 9–11 years (238 epg). The prevalence and geometric mean intensity of infection among girls was lower (26%; 290 epg) compared to that of boys (29.6%; 463 epg) (t = 4.383, p < 0.05). Though 61%(225) of the pupils interviewed were aware of the existence of the disease, 78% (290)didn't know the mode of transmission and only 8% (30) of those found infected were aware of their infection status. In a multivariate logistic regression model, altitude and water source (crater lakes) were significantly associated with infection.</p> <p>Conclusion and recommendations</p> <p>The altitudinal threshold for <it>S. mansoni </it>transmission in Uganda has changed and use of crater water at an altitude higher than 1,400 m above sea level poses a risk of acquiring <it>S. mansoni </it>infection in western Uganda. However, further research is required to establish whether the observed altitudinal threshold change is as a result of climate change or other factors. It is also necessary to establish the impact this could have on the epidemiology of schistosomiasis and other vector-borne diseases in Uganda. In addition, sensitisation and mass treatment of the affected community is urgently required.</p

Microscale characterization of prostate biopsies tissues using optical coherence elastography and second harmonic generation imaging

© 2018 USCAP, Inc All rights reserved. Photonics, especially optical coherence elastography (OCE) and second harmonic generation (SHG) imaging are novel high-resolution imaging modalities for characterization of biological tissues. Following our preliminary experience, we hypothesized that OCE and SHG imaging would delineate the microstructure of prostate tissue and aid in distinguishing cancer from the normal benign prostatic tissue. Furthermore, these approaches may assist in characterization of the grade of cancer, as well. In this study, we confirmed a high diagnostic accuracy of OCE and SHG imaging in the detection and characterization of prostate cancer for a large set of biopsy tissues obtained from men suspected to have prostate cancer using transrectal ultrasound (TRUS). The two techniques and methods described here are complementary, one depicts the stiffness of tissues and the other illustrates the orientation of collagen structure around the cancerous lesions. The results showed that stiffness of cancer tissue was ∼57.63% higher than that of benign tissue (Young's modulus of 698.43±125.29 kPa for cancerous tissue vs 443.07±88.95 kPa for benign tissue with OCE. Using histology as a reference standard and 600 kPa as a cut-off threshold, the data analysis showed sensitivity and specificity of 89.6 and 99.8%, respectively. Corresponding positive and negative predictive values were 99.5 and 94.6%, respectively. There was a significant difference noticed in terms of Young's modulus for different Gleason scores estimated by OCE (P-value<0.05). For SHG, distinct patterns of collagen distribution were seen for different Gleason grade disease with computed quantification employing a ratio of anisotropic to isotropic (A:I ratio) and this correlated with disease aggressiveness

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic

In Vitro and In Vivo Anti-Inflammatory Activity of 17-O-Acetylacuminolide through the Inhibition of Cytokines, NF-κB Translocation and IKKβ Activity

BACKGROUND AND PURPOSE: 17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. EXPERIMENTAL APPROACH: Plant extracts were initially tested against LPS-stimulated release of tumor necrosis factor alpha (TNF-α) from murine macrophages (RAW264.7 cells). Based on bioassay-guided fractionation, the active compound was identified as AA. AA was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. The inhibition of a panel of inflammatory cytokines (TNF, IL-1β, IL-6, KC, and GM-CSF) by AA was assessed at the expression and the mRNA levels. Moreover, the effect of AA on the translocation of the transcription factor nuclear factor kappa B (NF-κB) was evaluated in LPS-stimulated RAW264.7 cells and in TNF-stimulated L929 cells. Subsequently, AA was tested in the inhibitor of NF-κB kinase beta (IKKβ) activity assay. Lastly, the anti-inflammatory activity of AA in vivo was evaluated by testing TNF production in LPS-stimulated Balb/c mice. KEY RESULTS: AA effectively inhibited TNF-α release with an IC(50) of 2.7 µg/mL. Moreover, AA significantly inhibited both NO production and iNOS expression. It significantly and dose-dependently inhibited TNF and IL-1β proteins and mRNA expression; as well as IL-6 and KC proteins. Additionally, AA prevented the translocation of NF-κB in both cell lines; suggesting that it is acting at a post receptor level. This was confirmed by AA's ability to inhibit IKKβ activity, a kinase responsible for activating NF-κB, hence providing an insight on AA's mechanism of action. Finally, AA significantly reduced TNF production in vivo. CONCLUSIONS AND IMPLICATIONS: This study presents the potential utilization of this compound, as a lead for the development of an anti-inflammatory drug

Increasing vegetable intakes: rationale and systematic review of published interventions

Purpose While the health benefits of a high fruit and vegetable consumption are well known and considerable work has attempted to improve intakes, increasing evidence also recognises a distinction between fruit and vegetables, both in their impacts on health and in consumption patterns. Increasing work suggests health benefits from a high consumption specifically of vegetables, yet intakes remain low, and barriers to increasing intakes are prevalent making intervention difficult. A systematic review was undertaken to identify from the published literature all studies reporting an intervention to increase intakes of vegetables as a distinct food group. Methods Databases—PubMed, PsychInfo and Medline—were searched over all years of records until April 2015 using pre-specified terms. Results Our searches identified 77 studies, detailing 140 interventions, of which 133 (81 %) interventions were conducted in children. Interventions aimed to use or change hedonic factors, such as taste, liking and familiarity (n = 72), use or change environmental factors (n = 39), use or change cognitive factors (n = 19), or a combination of strategies (n = 10). Increased vegetable acceptance, selection and/or consumption were reported to some degree in 116 (83 %) interventions, but the majority of effects seem small and inconsistent. Conclusions Greater percent success is currently found from environmental, educational and multi-component interventions, but publication bias is likely, and long-term effects and cost-effectiveness are rarely considered. A focus on long-term benefits and sustained behaviour change is required. Certain population groups are also noticeably absent from the current list of tried interventions

Modelling the spatial and seasonal distribution of suitable habitats of schistosomiasis intermediate host snails using Maxent in Ndumo area, KwaZulu-Natal Province, South Africa

Abstract Background Schistosomiasis is a snail-borne disease endemic in sub-Saharan Africa transmitted by freshwater snails. The distribution of schistosomiasis coincides with that of the intermediate hosts as determined by climatic and environmental factors. The aim of this paper was to model the spatial and seasonal distribution of suitable habitats for Bulinus globosus and Biomphalaria pfeifferi snail species (intermediate hosts for Schistosoma haematobium and Schistosoma mansoni, respectively) in the Ndumo area of uMkhanyakude district, South Africa. Methods Maximum Entropy (Maxent) modelling technique was used to predict the distribution of suitable habitats for B. globosus and B. pfeifferi using presence-only datasets with ≥ 5 and ≤ 12 sampling points in different seasons. Precipitation, maximum and minimum temperatures, Normalised Difference Vegetation Index (NDVI), Normalised Difference Water Index (NDWI), pH, slope and Enhanced Vegetation Index (EVI) were the background variables in the Maxent models. The models were validated using the area under the curve (AUC) and omission rate. Results The predicted suitable habitats for intermediate snail hosts varied with seasons. The AUC for models in all seasons ranged from 0.71 to 1 and the prediction rates were between 0.8 and 0.9. Although B. globosus was found at more localities in the Ndumo area, there was also evidence of cohabiting with B. pfiefferi at some of the locations. NDWI had significant contribution to the models in all seasons. Conclusion The Maxent model is robust in snail habitat suitability modelling even with small dataset of presence-only sampling sites. Application of the methods and design used in this study may be useful in developing a control and management programme for schistosomiasis in the Ndumo area

Coronin-1A Links Cytoskeleton Dynamics to TCRαβ-Induced Cell Signaling

Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of αβT cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-κB (IκB). Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts αβT cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages