The role of Ki67 proliferation assessment in predicting local control in bladder cancer patients treated by radical radiation therapy.

PURPOSE: To assess whether tumour proliferation as measured by Ki67 immunostaining has any predictive value for local control in bladder cancer patients treated by radiotherapy. PATIENTS AND METHODS: Fifty-five patients suffering from infiltrating bladder carcinoma recommended for radical radiotherapy (66 Gy/6-7 weeks) were included in this study. Paraffin-embedded pre-treatment tumour sections were stained with the Ki67 antibody. The percentage of Ki67-positive nuclei was correlated with established prognostic factors, local control and survival. RESULTS: The Ki67 index was not related to local control in our patients when the median was selected as the cut-off value. Patients with tumours with a very low (<27%) Ki67 index had better local control at 5 years (69%) than patients with tumours with greater (>27%) Ki67 expression indices (31.5%) (P<0.05; log-rank test). CONCLUSIONS: Ki67 immunostaining was a feasible method to estimate tumour proliferation. Patients with very low proliferating tumours seemed to achieve better local control after fractionated radiotherapy compared to other patients. Further studies are needed with a greater number of patients to accurately define the role of Ki67 expression in predicting tumour repopulation during fractionated radiotherapy.     

Durability of Reinforced Concrete with Additions of Natural Pozzolans of Volcanic Origin

In this work, the properties of concrete modified with dosages of natural pozzolans (NP) in substitution of cement or superfine aggregates were evaluated. Proportions of 20/80 pozzolan/cement or pozzolan/superfine aggregates were selected for the additions of quarry and tuff pozzolans. Pozzolanic activity, durability, compressive strength, characteristic resistance, settling consistency, density, electrical resistivity, depth of water penetration, accessible porosity, and carbonation and chloride penetration were determined for the resulting concrete mixtures, and they were subsequently compared to the values obtained for the reference concrete batches without additions. The results of the cementitious mixtures supplemented with tuff (PZT) and quarry (PZQ) pozzolans, expressed in mmol/L, are consistent with the pozzolanism test, with [Ca(OH)₂]/[OH⁻] ratios at 7 days are 6.03/60.19 for PZQ and 1.78/92.78 PZT. In addition to the pozzolanic activity at these dosages, the characteristic resistance and durability parameters required by EHE-08 were verified. Particular attention was given to the determination of the diffusion of chloride ions, introducing an instrumental modification of the accelerated integral method. The modification provides values of diffusion coefficients similar to those obtained by the other methods with the advantage of greater stability and quality of the measurement.     

Protein/Fiber Index Modulates Uremic Toxin Concentrations in Hemodialysis Patients

Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), two uremic toxins (UTs), are associated with increased mortality in patients with chronic kidney disease (CKD). These toxins are produced by the microbiota from the diet and excreted by the kidney. The purpose of this study was to analyze the effect of diet on IS and PCS concentration in hemodialysis (HD) patients. Methods: We performed a prospective monocentric study using a seven-day diet record and determination of serum IS and PCS levels in HD patients. We tested the association between toxin concentrations and nutritional data. Results: A total of 58/75 patients (77%) completed the diet record. Mean caloric intake was 22 ± 9.2 kcal/kg/day. The protein/fiber index was 4.9 ± 1.8. No correlation between IS or PCS concentration and protein/fiber index was highlighted. In the 18 anuric patients (31%) in whom residual renal function could not affect toxin concentrations, IS and PCS concentrations were negatively correlated with fiber intake and positively correlated with the protein/fiber index. In a multivariate analysis, IS serum concentration was positively associated with the protein/fiber index (p = 0.03). Conclusions: A low protein/fiber index is associated with low concentrations of uremic toxins in anuric HD patients. Diets with an increased fiber intake must be tested to determine whether they reduce PCS and IS serum concentrations.     

Including the voice of paediatric patients: Cocreation of an engagement game

BackgroundEngaging patients in health care, research and policy is essential to improving patient‐important health outcomes and the quality of care. Although the importance of patient engagement is increasingly acknowledged, clinicians and researchers still find it difficult to engage patients, especially paediatric patients. To facilitate the engagement of children and adolescents in health care, the aim of this project is to develop an engagement game.MethodsA user‐centred design was used to develop a patient engagement game in three steps: (1) identification of important themes for adolescents regarding their illness, treatment and hospital care, (2) evaluation of the draft version of the game and (3) testing usability in clinical practice. Adolescents (12–18 years) were engaged in all steps of the development process through focus groups, interviews or a workshop. These were audio‐recorded, transcribed verbatim and analysed in MAXQDA.Results(1) The important themes for adolescents (N = 15) were included: visiting the hospital, participating, disease and treatment, social environment, feelings, dealing with staff, acceptation, autonomy, disclosure and chronically ill peers. (2) Then, based on these themes, the engagement game was developed and the draft version was evaluated by 13 adolescents. Based on their feedback, changes were made to the game (e.g., adjusting the images and changing the game rules). (3) Regarding usability, the pilot version was evaluated positively. The game helped adolescents to give their opinion. Based on the feedback of adolescents, some last adjustments (e.g., changing colours and adding a game board) were made, which led to the final version of the game, All Voices Count.ConclusionsWorking together with adolescents, All Voices Count, a patient engagement game was developed. This game provides clinicians with a tool that supports shared decision‐making to address adolescents'' wishes and needs.Patient or Public ContributionPaediatric patients, clinicians, researchers, youth panel of Fonds NutsOhra and patient associations (Patient Alliance for Rare and Genetic Diseases, Dutch Childhood Cancer Organization) were involved in all phases of the development of the patient engagement game—from writing the project plan to the final version of the game.     

Investigation of the in vitro and ex vivo acetylcholinesterase and antioxidant activities of traditionally used Lycopodium species from South America on alkaloid extracts

Ethnopharmacological relevance

The study was aimed at evaluating medicinal and therapeutic potentials of two Lycopodiaceae species, Lycopodium clavatum (L.) and Lycopodium thyoides (Humb. & Bonpl. ex Willd), both used in South American folk medicine for central nervous system conditions. Alkaloid extracts were evaluated for chemical characterization, acetylcholinesterase and antioxidant activities.

Materials and methods

The alkaloid extracts obtained by alkaline extraction were determined for each species by GC/MS examination. The evaluation of the anticholinesterase and the antioxidant activities of the extracts were tested by determining in vitro and ex vivo models. Effects on acetylcholinesterase (AChE) were tested in vitro using rat brain homogenates and ex vivo after a single administration (25, 10 and 1 mg/kg i.p.) of the alkaloid extracts in mice. The in vitro antioxidant effects were tested for the 2-deoxyribose degradation, nitric oxide (NO) interaction, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and total reactive antioxidant potential (TRAP). After an acute administration (25 and 10 mg/kg i.p.) of the extracts in middle-aged (12 months) mice, the antioxidant effects were estimated through the thiobarbituric acid reactive substances test (TBARS), and the antioxidant enzymes activities for catalase (CAT) and superoxide dismutase (SOD) were measured.

Results

AChE activity was inhibited in vitro by the alkaloid-enriched extracts of both Lycopodium species in a dose and time-dependent manner in rat cortex, striatum and hippocampus. A significant inhibition was also observed in areas of the brain after acute administration of extracts, as well as decreased lipid peroxidation and increased CAT activity in the cortex, hippocampus and cerebellum. A moderate antioxidant activity was observed in vitro for the extracts. Chemically, the main alkaloids found for the two species were lycopodine and acetyldihidrolycopodine.

Conclusion

This study showed that the biological properties of the folk medicinal plants Lycopodium clavatum and Lycopodium thyoides include AChE inhibitory activity and antioxidant effects, two possible mechanisms of action in Alzheimer's related processes.     

Apical hypertrophic cardiomyopathy with left ventricular apical aneurysm: Importance of multi‐modality imaging

Apical hypertrophic cardiomyopathy (HCM) is an uncommon variant of HCM characterized by apical hypertrophy without the septal predominance seen in the majority of HCM cases. In 2% of patients, a concomitant left ventricular apical aneurysm is observed, which increases the risk of sudden death and adverse HCM‐related events. Multimodality imaging is helpful for appropriate identification of this particular morphologic pattern. Herein, we present a case of apical HCM with a left ventricular apical aneurysm, exemplifying the utility of a multimodality approach from resting electrocardiogram, transthoracic echocardiogram, left ventriculography, and cardiac magnetic resonance imaging, for proper risk stratification and treatment planning.     

Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16)

The aims of the present study were (i) to assess the in vitro genetic stability of S19 and RB51 Brucella abortus vaccines strains and (ii) to evaluate the ability of multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) as a tool to be used in the quality control of live vaccines against brucellosis. Sixty-three batches of commercial S19 (n = 53) and RB51 (n = 10) vaccines, produced between 2006 and 2009, were used in this study. S19 and RB51 vaccines were obtained from, respectively, seven and two different manufacturers. Ten in vitro serial passages were performed on reference strains and on selected batches of commercial vaccines. All batches, reference strains and strains of serial passages were typed by the MLVA16. The results demonstrated that B. abortus S19 and RB51 vaccine strains are genetically stable and very homogeneous in their respective groups. Anyway, batches of S19 from one manufacturer and batches of RB51 from another presented genotypes distincts from the reference vaccine strains. In both cases, differences were found on locus Bruce07, which had addition of one repeat unit in the case of S19 batches and the deletion of one repeat unit in the case of RB51 batches. In summary, MLVA16 proved to be a molecular tool capable of discriminating small genomic variations and should be included in in vitro official tests.