Knowledge Levels, Attitude and Beliefs of Men towards the Digital Rectal Examinations (DRE): A study in Trinidad

Background: Trinidad and Tobago have been ranked as having one of the highest cancer mortality rates in the Caribbean. Prostate cancer was identified as the most common cancer in men, with a higher mortality than any other cancer. At least 1 in 9 men in Trinidad and Tobago will be diagnosed with prostate cancer during his lifetime. Purpose: The purpose of this study is to determine knowledge levels, attitudes, and beliefs of men aged 40 years and over regarding digital rectal examination (DRE). The investigators considered this crucial following the scourge of prostate cancer in Trinidad and Tobago and an apparent lack of the use of the DRE, a noted method of screening for the condition for early detection. Methods: A cross-sectional descriptive study was undertaken using 216 men who were at least 40 years old and who gave their informed consent; these men were attending a central mall in Trinidad in the month of April 2018 when the data was collected. Data was collected using the researchers’ designed, self-administered questionnaire and analysed using SPSS version 20. Result: Results indicate that most men (95.8%) are knowledgeable/very knowledgeable about DRE. Similarly, most (64.6%) of the men have favourable/very favourable attitudes towards DRE while 59.3% of them indicated that their beliefs have little or major influence regarding their participation in DRE. It also showed that the men’s beliefs are associated with their ethnicity (pDiscussion/Recommendation/Conclusion: The findings suggest that perhaps the attitudes and beliefs of men aged 40 years and over attending this mall are better predictors of intentions than their knowledge. This needs to be explored further given the need to curb the prevalence of prostate cancer amongst men in Trinidad and Tobago

Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments

Spatial patterning of proteins is a valuable technique for many biological applications and is the prevailing tool for defining microenvironments for cells in culture, a required procedure in developmental biology and tissue engineering research. However, it is still challenging to achieve protein patterns that closely mimic native microenvironments, such as gradient protein distributions with desirable mechanical properties. By combining projection dynamic mask lithography and protein engineering with non-canonical photosensitive amino acids, we demonstrate a simple, scalable strategy to fabricate any user-defined 2D or 3D stable gradient pattern with complex geometries from an artificial extracellular matrix (aECM) protein. We show that the elastic modulus and chemical nature of the gradient profile are biocompatible and allow useful applications in cell biological research

Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia

International audienceThe tumour suppressor gene PTEN is commonly altered in T-cell acute lymphoblastic leukaemia but its prognostic impact is still debated. We screened a cohort of 573 fully characterised adult and paediatric T-cell acute lymphoblastic leukaemia (TALL) patients for genomic PTEN abnormalities. PTEN-inactivating mutations and/or deletions were identified in 91 cases (16%), including 18% of paediatric (49/277) and 14% of adult cases (42/296). Thirty-four patients harboured only mutations, 12 cases demonstrated only large deletions and 9 only microdeletions. About 36 patients had combined alterations. Different mechanisms of PTEN inactivation predicted differences in the clinical outcome for both adult and paediatric patients treated according to the GRAALL03/05 and FRALLE2000 protocols. Whereas large deletions predicted lower 5-year overall survival (P = 0.0053 in adults, P = 0.001 in children) and disease-free survival (P = 0.0009 in adults, P = 0.0002 in children), mutations were not associated with a worse prognosis. The prognostic impact of PTEN loss is therefore linked to the underlying type of genomic abnormality, both in adult and paediatric T-ALLs, demonstrating that detailed analysis of the type of abnormality type would be useful to refine risk stratification

Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization

Chronic pelvic pain of unknown etiology is a common clinical condition and may develop as a result of cross-sensitization in the pelvis when pathological changes in one of the pelvic organs result in functional alterations in an adjacent structure. The aim of the current study was to compare transient receptor potential vanilloid 1 (TRPV1) activated pathways on detrusor contractility in vivo and in vitro using a rat model of pelvic organ cross-sensitization. Four groups of male Sprague-Dawley rats (N = 56) were included in the study. Animals received intracolonic saline (control), resiniferatoxin (RTX, TRPV1 agonist, 10−7 M), 2,4,6-trinitrobenzene sulfonic acid (TNBS, colonic irritant), or double treatment (RTX followed by TNBS). Detrusor muscle contractility was assessed under in vitro and in vivo conditions. Intracolonic RTX increased the contractility of the isolated detrusor in response to electric field stimulation (EFS) by twofold (P ≤ 0.001) and enhanced the contractile response of the bladder smooth muscle to carbachol (CCh). Acute colonic inflammation reduced detrusor contractility upon application of CCh in vitro, decreased bladder capacity by 28.1% (P ≤ 0.001), and reduced micturition volume by 60% (P ≤ 0.001). These changes were accompanied by an increased number of nonmicturition contractions from 3.7 ± 0.7 to 15 ± 2.7 (N = 6 in both groups, P ≤ 0.001 vs. control). Desensitization of intracolonic TRPV1 receptors before the induction of acute colitis restored the response of isolated detrusor strips to CCh but not to EFS stimulation. Cystometric parameters were significantly improved in animals with double treatment and approximated the control values. Our data suggest that acute colonic inflammation triggers the occurrence of detrusor instability via activation of TRPV1-related pathways. Comparison of the results obtained under in vitro vs. in vivo conditions provides evidence that intact neural pathways are critical for the development of an overactive bladder resulting from pelvic organ cross talk

Harnessing the MYB-dependent TAL1 5’super-enhancer for targeted therapy in T-ALL

Abstract The acquisition of genetic abnormalities engendering oncogene dysregulation underpins cancer development. Certain proto-oncogenes possess several dysregulation mechanisms, yet how each mechanism impacts clinical outcome is unclear. Using T-cell acute lymphoblastic leukemia (T-ALL) as an example, we show that patients harboring 5’super-enhancer (5’SE) mutations of the TAL1 oncogene identifies a specific patient subgroup with poor prognosis irrespective of the level of oncogene dysregulation. Remarkably, the MYB dependent oncogenic 5’SE can be targeted using Mebendazole to induce MYB protein degradation and T-ALL cell death. Of note Mebendazole treatment demonstrated efficacy in vivo in T-ALL preclinical models. Our work provides proof of concept that within a specific oncogene driven cancer, the mechanism of oncogene dysregulation rather than the oncogene itself can identify clinically distinct patient subgroups and pave the way for future super-enhancer targeting therapy

Prognostic value and oncogenic landscape of TP53 alterations in adult and pediatric T-ALL.

International audienc