Surveillance colonoscopy for Lynch syndrome in the Northern Cape: Does direct contact improve compliance?

Introduction The Annual Northern Cape Colonoscopy Outreach program provides surveillance colonoscopy to high–risk individuals known with Lynch Syndrome along the west coast and in the Northern Cape Province of South Africa. There are currently over 100 known mutation positive individuals. Surveillance colonoscopies are performed annually in August/September, and are preceded a by a preparation visit approximately 6-8 weeks prior. The aim of the preparation trip has been to directly impart information, regarding preparation and importance of attendance, to individuals required to attend annual surveillance. During the preparation trip an attempt is made to reach all individuals scheduled for surveillance but due to the vastness of the Northern Cape inevitably every year some areas are not visited. It has been noted that over the past few years fewer than 25 % of the total participants obtained 100 % adherence to surveillance. Objectives The primary objective of this study is to determine whether there is a need for a yearly colonoscopy preparation visit to high–risk individuals in the Northern Cape. The study determines if direct interaction with patients prior to surveillance colonoscopy will significantly impact attendance and adequacy of bowel preparation. Methods Seventy-eight individuals known with a genetic mutation for Lynch syndrome were enrolled in this randomised crossover trial spanning two years of surveillance. The control group (Group A) of individuals had bowel preparation and instructions forwarded to their local clinics and distributed to them via clinic or hospital staff. The test group (Group B) of individuals were personally visited and provided with instructions and bowel preparation by the research team. A measurement of attendance at surveillance colonoscopy as well as cleanliness of the colon was recorded. The study spanned two years of colonoscopy surveillance, July 2014 to September 2015, with a crossover of the control and test groups. Results The study cohort consisted of 28 (36%) male and 50 (64%) female participants with a median age of 39.5 years. Groups A and B consisted of 38 and 40 participants respectively. In September 2014 thirty-six (46.2%) participants presented for annual surveillance colonoscopy, 19 (50%) from the control group (Group A) and 17 (42.5%) from the intervention group (Group B). In 2015 there were 41 (53%) compliant individuals; this included 21 (55%) individuals receiving a preparatory direct contact visit (Group A), and 20 (50%) individuals from the 2015 control group B. Following exclusion of carry-over and period effect, the study intervention was found not to significantly impact attendance (p-value = 0.853). Superior attendance was noted in individuals with prior compliance to surveillance (p-value = 0.001). Conclusions Direct interaction with known Lynch syndrome individuals prior to annual surveillance colonoscopy has not shown to positively impact attendance. Interaction and counselling should focus on individuals identified to be defaulting surveillance

A Batch Digester Plant for Biogas Production and Energy Enhancement of Organic Residues from Collective Activities

Abstract An innovative little-sized batch biogas plant has been recently developed by the Italian Biomass Research Centre. It was fed by the residual biomass (agriculture residues and zootechnical wastes) produced by a farm located in the countryside of Perugia, Italy. The successful experience allowed the research group to design an upgrade of the existing plant, making it replicable to every communitarian activity such as Conference Halls, Schools, Condos, where organic biomass is produced as waste. Biomass recovery from markets, canteens and little food companies represents an opportunity for the installation of new residues-powered plants, achieving the production of both electricity and thermal energy for house heating and industrial processes. The collected biomass could also be integrated with pruning or residual biomass from the maintenance of the green and the neighbouring municipal wastewater from a septic tank. The simplicity, automaticity, and the cost-effectiveness of the plant, together with the incentives from electric energy injection to the grid, made the investment payable in a few years, allowing the operator to gain from renewable sources. Little sized biogas plants solves the problem of harvesting and disposal of the organic waste, reducing its transportation costs and producing green energy. The paper presents the preliminary design of the plant

Pharmacokinetics of sumatriptan in non-respondent and in adverse drug reaction reporting migraine patients

Sumatriptan is a selectiveagonist of 5HT1 (1B/1D) receptors,which has proved to be effectiveand safe for the acute treatment ofmigraine attacks. Nevertheless, itsuse by migraine sufferers is stilllimited and some patients consideradverse reactions related to sumatriptan,especially chest symptoms,unacceptable even if not serious.Moreover, in clinical trials, almostone third and one sixth of patients,respectively, fail to experienceheadache relief either after oral orafter subcutaneous sumatriptanadministration. Our aim was to verifywhether differencies in sumatriptanpharmacokinetics couldexplain non-response and/oradverse drug reactions. Sumatriptanlevels were determined by HPLCwith electrochemical detection.Pharmacokinetic parameters werecalculated using a computer program(PK Solutions 2.0; non compartmentalPharmacokinetics DataAnalysis). After oral administration,sumatriptan is rapidly absorbed andsometimes displays multiple peaksof plasma concentration. This “multiplepeaking” gives rise to considerableinter-subject variability inthe time of reaching maximumplasma concentration.Pharmacokinetic parameters ofsumatriptan, both after oral andsubcutaneous administration, weresimilar in the three patient groups.Blood pressure and heart rate didnot show any significant differencesbetween groups. Pharmacokineticparameters and bioavailability ofsumatriptan did not seem to be correlatedeither to the lack of efficacyor the appearance of side effects.These results could depend on thelimited number of patients studied

Quantitative Microbial Risk Assessment as support for bathing waters profiling

Profiling bathing waters supported by Quantitative Microbial Risk Assessment (QMRA) is key to the WHO's recommendations for the 2020/2021 revision of the European Bathing Water Directive. We developed an areaspecific QMRA model on four pathogens, using fecal indicator concentrations (E. coil, enterococci) for calculating pathogen loads. The predominance of illness was found to be attributable to Human Adenovirus, followed by Salmonella, Vibrio, and Norovirus. Overall, the cumulative illness risk showed a median of around 1 case/10000 exposures. The risk estimates were strongly influenced by the indicators that were used, suggesting the need for a more detailed investigation of the different sources of fecal contamination. Area-specific threshold values for fecal indicators were estimated on a risk-basis by modelling the cumulative risk against E. coll. and enterococci concentrations. To improve bathing waters assessment, we suggest considering source apportionment locally estimating of pathogen/indicator ratios, and calculating site-specific indicators thresholds based on risk assessment

Surface Melting Drives Fluctuations in Airborne Radar Penetration in West Central Greenland

Greenland Ice Sheet surface melting has increased since the 1990s, affecting the rheology and scattering properties of the near‐surface firn. We combine firn cores and modeled firn densities with 7 years of CryoVEx airborne Ku‐band (13.5 GHz) radar profiles to quantify the impact of melting on microwave radar penetration in West Central Greenland. Although annual layers are present in the Ku‐band radar profiles to depths up to 15 m below the ice sheet surface, fluctuations in summer melting strongly affect the degree of radar penetration. The extreme melting in 2012, for example, caused an abrupt 6.2 ± 2.4 m decrease in Ku‐band radar penetration. Nevertheless, retracking the radar echoes mitigates this effect, producing surface heights that agree to within 13.9 cm of coincident airborne laser measurements. We also examine 2 years of Ka‐band (34.5 GHz) airborne radar data and show that the degree of penetration is half that of coincident Ku‐band

The novel p53 target gene IRF2BP2 participates in cell survival during the p53 stress response

The tumor suppressor p53 contributes to the cellular fate after genotoxic insults, mainly through the regulation of target genes, thereby allowing e.g. repair mechanisms resulting in cell survival or inducing apoptosis. Unresolved so far is the issue, which exact mechanisms lead to one or the other cellular outcome. Here, we describe the interferon regulatory factor-2-binding protein-2 (IRF2BP2) as a new direct target gene of p53, influencing the p53-mediated cellular decision. We show that upregulation of IRF2BP2 after treatment with actinomycin D (Act.D) is dependent on functional p53 in different cell lines. This occurs in parallel with the down-regulation of the interacting partner of IRF2BP2, the interferon regulatory factor-2 (IRF2), which is known to positively influence cell growth. Analyzing the molecular functions of IRF2BP2, it appears to be able to impede on the p53-mediated transactivation of the p21- and the Bax-gene. We show here that overexpressed IRF2BP2 has an impact on the cellular stress response after Act.D treatment and that it diminishes the induction of apoptosis after doxorubicin treatment. Furthermore, the knockdown of IRF2BP2 leads to an upregulation of p21 and faster induction of apoptosis after doxorubicin as well as Act.D treatment

Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation

Background & Aims: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation. Methods: ILCs were isolated from colons of Tbx21-/- × Rag2-/- mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota. Results: IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner. Conclusions: IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells

Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey

Objective: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. The aim of this study was to assess the prevalence of SMA and treatment prescription in Italy. Methods: An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected. Results: One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%). Discussion: The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario