31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Horseshoe Kidney with Hydronephrosis – Tales of the Unexpected

Horseshoe kidney is an inborn renal fusion anomaly. It is frequently associated with renal stones and infections. The diagnosis is made using imaging methods - ultrasound, X-ray of the abdomen and intravenous pyelography, computed tomography (CT), magnetic resonance imaging (MRI) and radionuclide investigations. The diagnosis sometimes is hard, especially when other abnormalities are present, i.e. hydronephrosis, nephrolithiasis, stenosis of the ureteropelvic junction, etc. The authors present a male patient with horseshoe kidney and unilateral hydronephrosis due to obstruction of the ureteropelvic junction and discuss the diagnosis of horseshoe kidney and the diagnostic approach in such patients

DISCOLORATION OF REACTIVE DYES IN WASTEWATERS BY OZONATION

Three different reactive dyes - Reactive Blue 19, Reactive Orange 16 and Reactive Red 180 were dissolved in water separately in concentration 0.04g/l as model pollutants for contaminated wastewaters from textile industry. Every wastewater sample was treated by ozone with concentration 2000 ppm for 30 minutes at ambient temperature and the effect of discoloration was traced after 5, 10, 20 and 30 minutes. The highest degree of discoloration was obtained for Reactive Blue 19 model water pollutant dye where 98% discoloration was reached after 5 minutes ozonation and 99% after 30 minutes treatment, while the lowest discoloration was observed for Reactive Orange 16 – 84% after 30 minutes treatment. The discoloration degree for the three sample solutions in the whole time interval was as follows: Reactive Blue 19 > Reactive Red 180 > Reactive Orange 16. In summary it can be concluded than application of ozone treatment for wastewaters, containing different reactive dyes is very effective and practically applicable

Dependence of the textural properties and surface species of ZnO photocatalytic materials on the type of precipitating agent used in the hydrothermal synthesis

Three different precipitating agents (NaOH, NH4(H)CO3 and CO(NH2)2) have been applied for the hydrothermal synthesis of ZnO powder materials, aiming at obtaining various types of porosity and surface species on ZnO. The synthesis procedures were carried out in the presence and in the absence of tri-block copolymer Pluronic (P123, EO20PO70EO20). These materials were characterized by powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM)–energy-dispersive X-ray spectroscopy (EDX), BET method and TG–differential thermal analysis (DTA) method, and their photocatalytic activities were tested in the removal of azo dye Reactive Black 5 (RB5). The urea precipitant yields spongy-like surface forms and the greatest share of mesopores. It has the highest specific surface area, the highest degree of crystallinity of wurtzite ZnO phase and largest content of surface OH groups in comparison with the other two precipitants. The zinc hydroxycarbonate intermediate phase is missing in the case of NaOH as a precipitating agent; therefore, it manifests poorer textural characteristics. The morphology of P123-modified sample is different and consists of needle-shaped particles. The urea-precipitated samples display superior performance in the photocatalytic oxidation reaction, compared with the other precipitated samples. The other two precipitating agents are inferior in regard to their photocatalytic activity due to a greater share of micropores (not well-illuminated inner surface) and different surface morphologies

Reducing stigma and discrimination associated with COVID-19: early stage pandemic rapid review and practical recommendations

Aims To develop recommendations for strategies and interventions to reduce stigma and discrimination related to COVID-19, through reviewing and synthesising evidence in relation to COVID-19 and other disease outbreaks and infectious/stigmatised conditions from systematic reviews and primary studies and recommendations from additional materials. Methods Rapid review, drawing on the World Health Organization’s (WHO) methodology for developing interim guidelines during health emergencies. PubMed/MEDLINE, PsycINFO, Cochrane Central and Campbell Collaboration searched up to mid-April 2020. Searches were supplemented by referencesearching and expert recommendations. Searches were designed to identify: (1) systematic reviews (<10 years), or (2) primary intervention-studies (no date limit) reporting evidence on anti-stigma interventions (in relation to COVID-19 or other infectious/stigmatised conditions), or (3) additional relevant materials. Data were extracted on population, intervention, outcome, and results. These data were compiled into evidence summary tables and narrative overviews. Recommendations on strategies for COVID-19 stigma-reduction were developed using the WHO 'Evidence to Decision’ framework approach. The review protocol was registered with PROSPERO (registration ID: CRD42020177677). Results The searches identified a total of 4150 potentially relevant records, from which 12 systematic reviews and 29 additional articles were included. Overarching considerations and specific recommendations focus on: 1) language/words used in relation to COVID-19 and affected people; 2) media/journalistic practices; 3) public health interventions; 4) targeted public health interventions for key groups; and 5) involving communities and key stakeholders. Conclusions These recommendations represent the first consolidated evidence-based guidance on stigma and discrimination reduction in relation to COVID-19. Mitigating the impact of stigma is critical in reducing distress and negative experiences, and strengthening communities’ resolve to work together during exceptional circumstances. Ultimately, reducing stigma helps addressing structural inequalities that drive marginalisation and exacerbate both health risks and the impact of stigma. Administrations and decision makers are urged to consider integrating these recommendations into the ongoing COVID-19 response

Acute Kidney Injury and Acute Renal Failure in Coronaviral Infection

In December 2019 a newly described single-stranded coronavirus, later named SARS-CoV-2, started its expansion around the world and subsequently caused a global pandemic, affecting the lives of millions of people worldwide. SARS-CoV-2 can bind multiple receptors on different cells and thus invade many target organs, including the respiratory and gastrointestinal mucous membranes, lungs, central nervous system, heart, etc. This virus can affect the kidney tissue both directly and as a consequence of other organ involvement or of the treatment administered, causing acute kidney injury and leaving long term squeals that worsen the prognosis. We describe three patients with acute kidney injury and subsequent acute renal failure at the background of coronaviral infection

Phonetic similarity of /s/ in native and second language: Individual differences in learning curves

Second language learners may merge similar sounds from their native (L1) and second (L2) languages into a single phonetic category, neutralizing subphonemic differences in these similar sounds. This study investigates whether Dutch speakers produce phonetically distinct variants of /s/ in their L1 Dutch and L2 English, and whether and how this phonetic categorization develops over time. Target /s/ sounds in matching words in L1 and L2 were compared in their centre of spectral gravity. Speakers varied in their individual learning curves in the categorization of produced /s/ sounds, both in starting points and in longitudinal trajectories. After 3 years, however, all speakers had converged in producing their /s/ variants in L1 and L2 as two similar but different sounds