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IntroductionChronic exposure to arsenic through drinking water has been linked to several cancers. The metabolism of arsenic is thought to play a key role in arsenic-related carcinogenesis as metabolites of varying toxicity are produced and either stored in or excreted from the body. Atlantic Canada has the highest age-standardized incidence rates of all cancers in the country. This may be due to its high levels of environmental arsenic and the prevalence of unregulated private wells for water consumption. Here, we aimed to characterize the profiles of arsenic species and metallome in the toenails of four cancer groups, compare them to healthy participants (N = 338), and assess potential associations between the profiles with cancer prevalence.MethodsThis study employed a case–control design. Toenail samples and questionnaire data from cases (breast, cervical, prostate, and skin cancers) and controls were sourced from the Atlantic Partnership for Tomorrow’s Health (PATH) cohort study. The levels of arsenic species were measured using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) paired with High Performance Liquid Chromatography (HPLC) and total concentrations of metallome (23 metals) were determined by ICP-MS separately. Multivariate analyses were conducted to compare cases with controls within each cancer group.ResultsArsenic speciation profiles varied by cancer type and were significantly different between cases and controls in the breast (p = 0.0330), cervical (p = 0.0228), and skin (p = 0.0228) cancer groups. In addition, the profiles of metallome (nine metals) were significantly differentiated in the prostate (p = 0.0244) and skin (p = 0.0321) cancer groups, with higher zinc concentrations among cases compared to controls.ConclusionHistory of cancer diagnosis was associated with specific profiles of arsenic species and metallome. Our results indicate that arsenic methylation and zinc levels, as measured in toenails, may be an important biomarker for cancer prevalence. Further research is needed to use toenails as a prognostic measure of arsenic-and other metal-induced cancer.

Chronic exposure to inorganic arsenic and trace metals has been linked to prostate cancer, and altered arsenic methylation capacity may have an important role in arsenic carcinogenesis. Biomarkers may be able to elucidate this role. Our objectives were to characterize profiles of arsenic species and metallome in toenails and urine samples, compare profiles between prostate cancer cases and controls, and determine the discriminant ability of toenail and urine biomarkers. Toenail samples (n = 576), urine samples (n = 152), and questionnaire data were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. Healthy controls were matched to prostate cancer cases (3:1 ratio) on sex, age, smoking status, and the province of residence. Metallome profiles and proportions of arsenic species were measured in toenail and urine samples. Analysis of covariance (ANCOVA) was used to compare the mean percent monomethylarsonic acid (%MMA), dimethylarsonic acid (%DMA), inorganic arsenic (%iAs), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). Multivariate analysis of covariance (MANCOVA) was used to compare selected metal concentrations. Mean %MMA was significantly lower and SMI was significantly higher in toenails from prostate cancer cases compared to controls in unadjusted and adjusted models. Proportions of arsenic species were correlated with total arsenic in toenails. Arsenic speciation in urine was not different between cases and controls, nor were metallome profiles in toenails and urine. Our results indicate that toenails are a viable biomarker for altered arsenic speciation in prostate cancer cases and may have greater utility than urine in this context.

Peptoids, N-substituted glycine oligomers, are a class of diverse and sequence-specific peptidomimetics with wide-ranging applications. Advancing the functional repertoire of peptoids to emulate native peptide and protein functions requires engineering peptoids that adopt regular secondary and tertiary structures. An understanding of how changes to peptoid sequence change structural features, particularly in water-soluble systems, is underdeveloped. To address this knowledge gap, five 15-residue water-soluble peptoids that include naphthalene-functionalized side chains were designed, prepared, and subjected to a structural study using a palette of techniques. Peptoid sequence designs were based on a putative amphiphilic helix peptoid bearing structure-promoting (S)-N-(1-naphthylethyl)glycine residues whose self-association in water has been studied previously. New peptoid variants reported here include sequence changes that influenced peptoid conformational flexibility, functional group patterning (amphiphilicity), and hydrophobicity. Peptoid structures were evaluated and compared using circular dichroism spectroscopy, fluorescence spectroscopy, and size exclusion chromatography. Spectral data confirmed that sequence changes alter peptoids' degree of assembly and the organization of self-assembled structures in aqueous solutions. Insights gained in these studies will inform the design of new water-soluble peptoids with regular structural features, including desirable higher-order (tertiary and quaternary) structural features.

Studies that identify a new supramolecular host for the highly toxic and prevalent carcinogen benzo[a]pyrene (BP) are reported here. By monitoring changes to absorption and fluorescence spectra, the interaction between BP and two peptoids (N-substituted glycine oligomers) of different length and self-association propensities were compared. Peptoid length and solvent choice influence spectral features. Observed trends support that peptoid self-association in aqueous solution generates a hydrophobic core to which BP can associate. [ABSTRACT FROM AUTHOR]

INTRODUCTION: les traumatismes fermés de l'abdomen sont fréquents. METHODES: il s'agissait d'une étude rétrospective sur 49 dossiers de patients opérés pour traumatisme fermé de l'abdomen en cinq ans à l'Hôpital General de Référence Nationale de N'Djaména au Tchad. Les paramètres épidémiologiques, cliniques et thérapeutiques étaient étudiés. RESULTATS: c'étaient 42 hommes et 7 femmes d'âge moyen de 21,3 ans. Les étiologies étaient: les accidents de la voie publique dans 61,2% des cas; les écroulements de mur (14,3%); les agressions (8,2%). Les traumatismes fermés de l'abdomen étaient plus fréquents au mois d'Août (14,28%) et Octobre (16,32%). Le délai d'admission à l'hôpital était de 6 à 12h dans 43% des cas. Le moyen d'évacuation des blessés était une voiture privée dans 85,7% des cas. Cliniquement, l'état hémodynamique était souvent stable (55,1%). L'imagerie médicale était dominée par la radiographie directe de l'abdomen (57,1%). Les lésions les plus observées ont été celles du grêle seul (16,32%) ou associées à celle de la vessie (8,16%), et de la rate (2,04%). La laparotomie était négative dans 6,12% des cas. La morbidité (12,2%) était dominée par les abcès de paroi. Le taux de décès était de 6,1%. CONCLUSION: les accidents de la voie publique sont la première cause de traumatismes fermés de l'abdomen. Le délai diagnostic et thérapeutique est important. Des mesures de sécurité routière devraient prévenir les accidents.

A desire to replicate the structural and functional complexity of proteins with structured, sequence‐specific oligomers motivates study of the structural features of water‐soluble peptoids (N‐substituted glycine oligomers). Understanding the molecular‐level details of peptoid self‐assembly in water is essential to advance peptoids' application as novel materials. Peptoid 1, an amphiphilic, putatively helical peptoid previously studied in our laboratory, shows evidence of self‐association in aqueous solution. In this work, we evaluate how changes to aqueous solution conditions influence the self‐association of 1. We report that changes to pH influence the fluorescence and CD spectroscopic features as well as the peptoid's interaction with a solvatochromic fluorophore and its apparent size as estimated by size exclusion chromatography. Addition of guanidine hydrochloride and ammonium sulfate also modulate spectroscopic features of the peptoid, its interaction with a solvatochromic fluorophore, and its elution in size exclusion chromatography. These data suggest that the ordering of the self‐assembly changes in response to pH and with solvent additives and is more ordered at higher pH and in the presence of guanidine hydrochloride. The deeper understanding of the self‐association of 1 afforded by these studies informs the design of new stimuli‐responsive peptoids with stable tertiary or quaternary structures. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains one of the most lethal malignancies, with limited treatment options and poor prognosis. A common characteristic among pancreatic cancer patients is the biomechanically altered tumor microenvironment (TME), which among others is responsible for the elevated mechanical stresses in the tumor interior. Although significant research has elucidated the effect of mechanical stress on cancer cell proliferation and migration, it has not yet been investigated how it could affect cancer cell drug sensitivity. Here, we demonstrated that mechanical stress triggers autophagy activation, correlated with increased resistance to oxaliplatin treatment in pancreatic cancer cells. Our results demonstrate that inhibition of autophagy using hydroxychloroquine (HCQ) enhanced the oxaliplatin-induced apoptotic cell death in pancreatic cancer cells exposed to mechanical stress. The combined treatment of HCQ with losartan, a known modulator of mechanical abnormalities in tumors, synergistically enhanced the therapeutic efficacy of oxaliplatin in murine pancreatic tumor models. Furthermore, our study revealed that the use of HCQ enhanced the efficacy of losartan to alleviate mechanical stress levels and restore blood vessel integrity beyond its role in autophagy modulation. These findings underscore the potential of co-targeting mechanical stresses and autophagy as a promising therapeutic strategy to overcome drug resistance and increase chemotherapy efficacy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Endourology plays an important role in modern urological practice. Compared to open surgery, it offers many advantages. In Africa, endourology is not widely practiced or non-existent in some referral centres. Several factors have been linked to this challenge. This article explores and proposes strategies to improve endourology practice in the African context. Recognising the unique challenges and opportunities in the region, the document discusses key initiatives and recommendations to promote the growth and development of endourological practices, including the identification of local needs, training, technological adaptation, etc. It aims to provide valuable information on the advancement of endourology in Africa., (© 2024 BJU International.)

Within the complex tumor microenvironment, cells experience mechanical cues-such as extracellular matrix stiffening and elevation of solid stress, interstitial fluid pressure, and fluid shear stress-that significantly impact cancer cell behavior and immune responses. Recognizing the significance of these mechanical cues not only sheds light on cancer progression but also holds promise for identifying potential biomarkers that would predict therapeutic outcomes. However, standardizing methods for studying how mechanical cues affect tumor progression is challenging. This challenge stems from the limitations of traditional in vitro cell culture systems, which fail to encompass the critical contextual cues present in vivo . To address this, 3D tumor spheroids have been established as a preferred model, more closely mimicking cancer progression, but they usually lack reproduction of the mechanical microenvironment encountered in actual solid tumors. Here, we review the role of mechanical forces in modulating tumor- and immune-cell responses and discuss how grasping the importance of these mechanical cues could revolutionize in vitro tumor tissue engineering. The creation of more physiologically relevant environments that better replicate in vivo conditions will eventually increase the efficacy of currently available treatments, including immunotherapies., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Our aim was to determine the current trend of endourology in the management of upper urinary tract calculi in Africa reference centres. We conducted an online multiple-choice questionnaire survey involving 46 centres from 27 countries using a structured well-designed Google Form (®) questionnaire. The questionnaires were distributed to the head of service through their emails. The questions collected demographic data about the centre, the epidemiology of urolithiasis, diagnostic means and management of upper urolithiasis, especially access to endourology procedures and their practices. Descriptive analyses were performed. The participation rate was 77.9%. Urinary lithiasis was one of the three main pathologies encountered in 42/46 centres. 33 centres had easy access to CT scanners and 34 had operating theatres equipped with endo-urological surgery equipment. Of these 34 centres, 30 perform endourology for the management of upper urinary tract stones. Rigid ureteroscopy is the main technique used by the centres. It is the only endourology technique used for stone management by 12 centres (40%). 7/30 (23.3%) have the option of performing rigid ureteroscopy, flexible ureteroscopy and percutaneous nephrolithotomy. The frequency of procedures varies widely, with 43.3% rarely performing endourological surgery. Seventeen centres have their operating theatre equipped with a fluoroscope and 6/42 centres have extracorporeal lithotripsy. Open surgery is still used in 29/42 centres (69.1%). Laparoscopy is available in 50% of centres, but none reported performing laparoscopic lithotomy. In Africa, urinary lithiasis plays an important role in the activities of referral centres. Modern management techniques are used to varying degrees (not all centres have them) and with very variable frequency. Open surgery is still widely performed as a management. Rigid ureteroscopy is the main endourological technique. It is essential to develop the practice of modern urology in Africa, mainly endourology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.