EXPLORING THE ROLE OF SULFORAPHANE IN PROSTATE METABOLISM

Prostate cancer is a worldwide health problem with a higher incidence in older men. Prostate cancer risk is lower in Asian countries compared to the west, this has largely been attributed to difference in diets between the two populations. To date evidence from casecontrol studies has indicated that cruciferous vegetables and regular exercise reduce the risk of prostate cancer progression; however, other similar studies have shown no association. These contrasting results may be due to study heterogeneity and the long latent period of prostate cancer. The aim of the work presented in this thesis is to further understand the role of sulforaphane, an isothiocyanate derived from broccoli plants in preventing prostate cancer by exploring its effect on the metabolic microenvironment of the prostate. One of the key metabolic pathways that is altered in prostate cancer is the Krebs� cycle. Citrate, a product of the Krebs� cycle accumulates in healthy prostate tissue and is reduced in prostate cancer. It was demonstrated by using a novel liquid chromatography and tandem mass spectrometry method that the levels of citrate within in vitro models of prostate cancer are markedly different to those of human tissue. Furthermore, citrate levels altered when prostate cells were exposed to reactive oxygen species. The addition of physiological quantities of sulforaphane to prostate cells in culture inhibited the reactive oxygen speciesmediated changes on the Krebs� cycle. A randomised, double-blinded human intervention study was undertaken to further understand the role of sulforaphane in prostate cancer by recruiting men with early prostate cancer into three different study arms delivering sulforaphane in increasing concentrations through naturally bred broccoli varieties. A subgroup analysis demonstrated significant metabolite changes in prostate tissue that were driven by the study diet with accumulation of sulfate common to all three arms. This was positively correlated with lower rates of cancer at 12 months. The work presented here strengthens the argument that sulforaphane in physiologically achievable concentrations can alter the metabolic environment of the prostate and that this may contribute to the cancer preventing properties of cruciferous vegetables

A renal colic fast track pathway to improve waiting times and outcomes for patients presenting to the emergency department

Introduction: Renal colic is commonly encountered in the emergency department (ED). We validated a fast track renal colic (FTRC) initiative to decrease patient waiting times and streamline patient flow. Method: The FTRC pathway was devised according to the National Institute for Health and Care Excellence clinical summary criteria for the management of patients with suspected renal colic. ED triage nurses use the pathway to identify patients with likely renal colic suitable for fast track to analgesia, investigation and management. Investigations, diagnosis and patient demographics were recorded for 1157 consecutive patients coded as renal colic at a single-center ED over 12 months. Results: Three hundred and two patients were suitable for the FTRC pathway (26.1%), while 855 were seen by the ED clinicians prior to onward referral. Also, 83.9% of patients underwent computed tomography scan. In the FTRC group, 57.3% of patients had radiologically confirmed calculi versus 53.8% in the non-FTRC group (p=0.31). Alternative diagnoses among FTRC patients (2.6%) included ovarian pathology (n=1), diverticulitis (n=2) and incidental renal cell carcinoma (n=2), while 26.1% had no identifiable pathology. No immediately life-threatening diagnoses were identified on imaging. Computed tomography scans performed in the non-FTRC group identified two ruptured abdominal aortic aneurysms and alternative diagnoses (2.57%) including ovarian pathology (n=7), cholecystitis (n=2), incidental renal cell carcinoma (n=3) and inflammatory bowel disease (n=1); 31.2% identified no pathology. Time in ED and time to radiologist-reported imaging were lower for the FTRC group versus non-FTRC group (p<0.0001). Conclusion: The FTRC pathway is a safe and efficacious method of reducing diagnostic delay and improving patient flow in the ED

Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention—results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial

Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. Results In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial–mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. Conclusion Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143

Major urological cancer surgery for patients is safe and surgical training should be encouraged during the COVID-19 pandemic : A multi-centre analysis of 30-day outcomes

Funding Information: Funding/Support and role of the sponsor: Wei Shen Tan is funded by the Urology Foundation . Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.COVID-19 has resulted in the deferral of major surgery for genitourinary (GU) cancers with the exception of cancers with a high risk of progression. We report outcomes for major GU cancer operations, namely radical prostatectomy (RP), radical cystectomy (RC), radical nephrectomy (RN), partial nephrectomy (PN), and nephroureterectomy performed at 13 major GU cancer centres across the UK between March 1 and May 5, 2020. A total of 598 such operations were performed. Four patients (0.7%) developed COVID-19 postoperatively. There was no COVID-19–related mortality at 30 d. A minimally invasive approach was used in 499 cases (83.4%). A total of 228 cases (38.1%) were described as training procedures. Training case status was not associated with a higher American Society of Anesthesiologists (ASA) score (p = 0.194) or hospital length of stay (LOS; p > 0.05 for all operation types). The risk of contracting COVID-19 was not associated with longer hospital LOS (p = 0.146), training case status (p = 0.588), higher ASA score (p = 0.295), or type of hospital site (p = 0.303). Our results suggest that major surgery for urological cancers remains safe and training should be encouraged during the ongoing COVID-19 pandemic provided appropriate countermeasures are taken. These real-life data are important for policy-makers and clinicians when counselling patients during the current pandemic. Patient summary: We collected outcome data for major operations for prostate, bladder, and kidney cancers during the COVID-19 pandemic. These surgeries remain safe and training should be encouraged during the ongoing pandemic provided appropriate countermeasures are taken. Our real-life results are important for policy-makers and clinicians when counselling patients during the COVID-19 pandemic.Peer reviewe

Influence of Fixed Orthodontic Therapy on Pharyngeal Airway Dimensions after Correction of Class-I, -II and -III Skeletal Profiles in Adolescents

The aim was to compare the influence of fixed orthodontic therapy (OT) on the pharyngeal airway space dimensions after correction of class-I, -II and -III skeletal profiles and among untreated adolescent patients. A control group comprising of untreated patients was also included. Demographics and OT-related information was retrieved from patients&rsquo; records. Measurements of airway spaces in the nasopharynx, oropharynx and hypopharynx were performed on lateral cephalograms. p-values under 0.05 were considered statistically significant. The results showed no statistically significant differences in the naso-, oro- and hypo-pharyngeal airway spaces among patients with class-I, -II and -III skeletal profiles and individuals in the control group. There were no statistically significant differences when naso-, oro- and hypo-pharyngeal airway spaces were compared among patients with class-I, -II and -III skeletal profiles. In conclusion, in non-extraction cases without maxillary expansion, fixed OT does not affect the naso-, oro- and hypo-pharyngeal airway spaces in patients with skeletal Class-I, -II and -III skeletal profiles. Further studies involving patients undergoing ME and premolar extraction are needed to elucidate the influence of fixed OT on the naso-, oro- and hypo-pharyngeal airway spaces

Green Synthesis and Pinning Behavior of Fe-Doped CuO/Cu2O/Cu4O3 Nanocomposites

Egg white-induced auto combustion has been used to synthesize undoped and Fe-doped CuO/Cu2O/Cu4O3 nanocomposites in a soft, secure, and one-pot procedure. X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR) investigations have been used to identify functional groups and the structural properties of crystalline phases present in the as-synthesized composites. Scanning Electron Microscopy/Energy Dispersive Spectrometry (SEM/EDS) elemental mapping analyses and Transmission Electron Microscopy (TEM) techniques were used to explore the morphological and compositional properties of these composites. N2-adsorption/desorption isotherm models have been used to examine the surface variables of the as-prepared systems. Based on the Vibrating Sample Magnetometer (VSM) technique, the magnetic properties of various copper-based nanocomposites were detected due to being Fe-doped. XRD results showed that the undoped system was composed of CuO as a major phase with Cu2O and Cu4O3 as second phases that gradually disappeared by increasing the dopant content. The crystalline phase&rsquo;s crystallographic properties were determined. The average particle size was reduced when the synthesized systems were doped with Fe. The construction of porous and polycrystalline nanocomposites involving Cu, Fe, O, and C components was confirmed by SEM/EDS and TEM measurements. In terms of the increase in magnetization of the as-manufactured nanocomposites due to Fe-doping, oxygen vacancies at the surface/or interfacial of nanoparticles, while also domain wall pinning mechanisms, were investigated. Finally, employing the investigated production process, Fe doping of CuO/Cu2O/Cu4O3 nanocomposite resulted in the development of a single phase (CuO) exhibiting &ldquo;pinned&rdquo; type magnetization. This is the first publication to show that CuO/Cu2O/Cu4O3

INTEGRATING TRANSCRIPTOME AND METABOLOME SIGNATURES TO PROVIDE NEW INSIGHTS AS TO HOW DIET CAN PREVENT PROSTATE CANCER PROGRESSION

Although there is an increase in the diagnosis of prostate cancer, most tumours remain organ-confined with little consequence to health. However, if highly aggressive clones emerge, this is a poor health prognosis. Genomic studies have demonstrated that many mutations occur in what appears to be non-cancerous tissues, and metastatic cancer may arise from relatively small tumours, with larger tumours remaining confined to the prostate. We are seeking to understand why the prostate gland becomes susceptible to multifocal carcinogenesis, and how diet may affect the tumour microenvironment to reduce the risk of emergence of aggressive clones. We report results from an intervention study designed to investigate dietary factors that reduce the risk of cancer progression. Men who had a diagnosis of organ-confined prostate cancer underwent a transperineally template biopsy before and after a 12-month dietary intervention with a soup developed from glucosinolate-enriched broccoli, along with appropriate control diets. Habitual diet was rigorously assessed through repeated seven-day diet diaries. Biopsy tissue was assessed for cancer progression, metabolome and transcriptome profiles, and quantification of targeted metabolites. The results provide insight into specific components of cruciferous vegetables that may influence the risk of cancer progression and the underlying mechanisms

Mesomorphic, Computational Investigations and Dyeing Applications of Laterally Substituted Dyes

Two groups of laterally substituted non-mesomorphic and liquid crystalline materials bearing monoazo group were prepared and investigated via experimental and theoretical techniques. The molecular structures of the designed dyes were evaluated by FT-IR and NMR spectroscopic analyses. Mesomorphic examinations for all synthesized dyes were investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). Results revealed that, the thermal and optical properties of investigated compounds are mainly dependent on their molecular geometry. The optimized geometries of the azo derivatives and their electronic absorption of the dyes were carried out using the B3LYP/6-311G level of the DFT method. The azo dyes were measured for their dyeing performance on polyester fabrics. The dyed fabrics have excellent fastness properties with a color strength of 1.49&ndash;3.43 and an exhaustion rate of 82&ndash;64%. The chemical descriptor parameters of disperse azo dyes in gas phase were calculated and correlated with dyeing parameters