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22 pages, 3036 KiB  
Article
Synthesis and Characterization of Transferrin Receptor-Targeted Peptide Combination SN-38 and Rucaparib Conjugate for the Treatment of Glioblastoma
by Perpetue Bataille Backer and Simeon Kolawole Adesina
Pharmaceutics 2025, 17(6), 732; https://doi.org/10.3390/pharmaceutics17060732 - 2 Jun 2025
Viewed by 820
Abstract
Background/Objectives: Glioblastoma represents a particularly aggressive and fatal type of brain tumor. Peptide-drug conjugates, which offer the promise of traversing the blood-brain barrier to selectively accumulate in tumor tissues and precisely target cancer cells, are an active area of research. We present the [...] Read more.
Background/Objectives: Glioblastoma represents a particularly aggressive and fatal type of brain tumor. Peptide-drug conjugates, which offer the promise of traversing the blood-brain barrier to selectively accumulate in tumor tissues and precisely target cancer cells, are an active area of research. We present the synthesis and characterization of the T7 peptide (HAIYPRH) as a targeting ligand for the transferrin receptor, which is highly expressed on both the blood-brain barrier and glioma cells. Methods: Using the T7 peptide, the synthesis, characterization, and biological evaluation of a transferrin receptor-targeted, combination SN-38 and rucaparib peptide drug conjugate (T7-SN-38-rucaparib) are described. Results: The T7 peptide drug conjugate readily cleaved in the presence of exogenous cathepsin B, releasing the active drug payloads. In vitro experiments demonstrated potent cytotoxic effects of the T7 peptide drug conjugate on glioblastoma cells (IC50 = 22.27 nM), with reduced toxicity to non-cancerous HEK 293 cells (IC50 = 115.78 nM), indicating selective toxicity toward cancer cells. Further investigations revealed that blocking transferrin receptors with drug-free T7 peptide significantly reduced the conjugate’s cytotoxicity, an effect that could be reversed by introducing exogenous cathepsin B to the cells. Conclusions: These findings highlight the potential of glioblastoma-targeted delivery of SN-38 and rucaparib based on specific recognition of the transferrin receptor for transport across the blood-brain barrier, offering the prospect of reduced toxicity and selective killing of cancer cells. Additionally, since rucaparib does not cross the blood-brain barrier, this work is significant to facilitate the use of rucaparib for the treatment of brain tumors. Full article
(This article belongs to the Special Issue Combination Therapy Approaches for Cancer Treatment)
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12 pages, 259 KiB  
Article
The Eye and the Flesh: Céline, Bataille, and the Fascination with Death
by Alexis Louis Chauchois
Humanities 2025, 14(4), 70; https://doi.org/10.3390/h14040070 - 24 Mar 2025
Viewed by 546
Abstract
This paper argues that Louis-Ferdinand Céline and Georges Bataille use voyeurism as a transgressive mechanism to confront death through the female body, a paradoxical site of life and decay. Though Céline’s clinical, disenchanted gaze contrasts with Bataille’s erotic, metaphysical quest, both employ the [...] Read more.
This paper argues that Louis-Ferdinand Céline and Georges Bataille use voyeurism as a transgressive mechanism to confront death through the female body, a paradoxical site of life and decay. Though Céline’s clinical, disenchanted gaze contrasts with Bataille’s erotic, metaphysical quest, both employ the act of seeing to reveal death’s presence within vitality. In Céline’s works, voyeurism shifts from erotic curiosity to cold observation, framing the female body as a sterile emblem of mortality. In Bataille’s, it becomes participatory, merging ecstasy with dissolution in a sacred yet destructive form. Drawing on Freud and Sodom motifs, this study shows how their gazes transform the female body into a lens for existential finitude, challenging life–death boundaries in 20th-century French literature. Full article
(This article belongs to the Section Literature in the Humanities)
19 pages, 2450 KiB  
Article
Myostatin Exacerbates Endothelial Dysfunction Induced by Uremic Toxin Indoxyl Sulfate and Is Associated with Hemodialysis Arteriovenous Access Complications
by Justine Solignac, Laetitia Dou, Rania Chermiti, Nathalie McKay, Philippe Giaime, Nathalie Pedinielli, Hamza Benjelloun, Guillaume Lano, Julien Mancini, Stéphane Burtey and Stanislas Bataille
Toxins 2025, 17(4), 159; https://doi.org/10.3390/toxins17040159 - 22 Mar 2025
Viewed by 588
Abstract
Hemodialysis patients exhibit endothelial dysfunction, contributing to elevated cardiovascular risk and complications of the arteriovenous access. These patients have elevated serum levels of myostatin, a member of the transforming growth factor-β (TGFβ) superfamily, and of the uremic toxin indoxyl sulfate, both of which [...] Read more.
Hemodialysis patients exhibit endothelial dysfunction, contributing to elevated cardiovascular risk and complications of the arteriovenous access. These patients have elevated serum levels of myostatin, a member of the transforming growth factor-β (TGFβ) superfamily, and of the uremic toxin indoxyl sulfate, both of which are pro-inflammatory towards endothelial cells. We hypothesized that myostatin and indoxyl sulfate may synergistically induce endothelial dysfunction by impairing endothelial proliferation and promoting a pro-inflammatory phenotype. We first investigated the effect of myostatin on cultured endothelial cells in the presence of indoxyl sulfate. We then examined the association between serum myostatin concentrations and the occurrence of cardiovascular and arteriovenous access complications in hemodialysis patients. In vitro, myostatin exhibited endotheliotoxic effects in the presence of a uremic concentration of indoxyl sulfate, enhanced its antiproliferative effect, and amplified MCP-1 and IL-8 chemokine upregulation. In patients, high myostatin concentrations correlated with indoxyl sulfate concentrations and were associated with an increased risk of arteriovenous access complications. These findings suggest that myostatin amplifies endothelial injury mediated by indolic uremic toxins and might contribute to AV access complications. Full article
(This article belongs to the Special Issue The Role of Uremic Toxins in Comorbidities of Chronic Kidney Disease)
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14 pages, 231 KiB  
Article
In the Lap of the Buddha: Intimacy in Tibetan Ritual
by Cameron David Warner
Religions 2025, 16(2), 202; https://doi.org/10.3390/rel16020202 - 8 Feb 2025
Viewed by 1545
Abstract
Following the re-opening of the Rasa Trulnang Tsuklhakhang, the central temple in Lhasa, all of the new images of Buddhas, bodhisattvas, and famous lamas were placed behind glass except for those in the sancta sanctorum, the “Jokhang”. When a pilgrim approaches the [...] Read more.
Following the re-opening of the Rasa Trulnang Tsuklhakhang, the central temple in Lhasa, all of the new images of Buddhas, bodhisattvas, and famous lamas were placed behind glass except for those in the sancta sanctorum, the “Jokhang”. When a pilgrim approaches the central figure, the Jowo Śākyamuni, she climbs a ladder on his right side, lays a ceremonial scarf across his lap, and then lays her head there, like a child seeking solace from her mother. A wealthy pilgrim might return in the late afternoon, when the temple is closed to visitors, to sponsor a regilding ceremony, in which the sponsor can spend up to an hour nearly alone with the Jowo watching his whole body be repainted in gold. Based on participant observation, pilgrimage guides, and verses of praise offered to the Jowo, this paper considers how the cult of the Jowo uses moments of private intimacy to bridge the distance, both physically and historically, between a devotee and the Buddha. Full article
(This article belongs to the Special Issue Materiality and Private Rituals in Tibetan and Himalayan Cultures)
25 pages, 50215 KiB  
Article
Source of Ore-Forming Fluids and Ore Genesis of the Batailing Au Deposit, Central Jilin Province, Northeast China: Constraints from Fluid Inclusions and H-O-C-S-Pb Isotopes
by Haoming Li, Keyong Wang, Xiangjin Yan, Qingying Zhao and Lixue Sun
Minerals 2024, 14(10), 1028; https://doi.org/10.3390/min14101028 - 14 Oct 2024
Viewed by 1060
Abstract
The Batailing Au deposit is a vein-type deposit in central Jilin Province, situated in the southern sector of the Lesser Xing’an–Zhangguangcai Range within the eastern Central Asian Orogenic Belt. NE-trending fault-controlled orebodies occur in the Upper Permian Yangjiagou Formation and quartz diorite–porphyrite. The [...] Read more.
The Batailing Au deposit is a vein-type deposit in central Jilin Province, situated in the southern sector of the Lesser Xing’an–Zhangguangcai Range within the eastern Central Asian Orogenic Belt. NE-trending fault-controlled orebodies occur in the Upper Permian Yangjiagou Formation and quartz diorite–porphyrite. The mineralisation process was delineated into three stages: (I) quartz–arsenopyrite–pyrite, (II) quartz–polymetallic sulphides (main Au mineralisation stage), and (III) quartz–pyrite–carbonate. Fluid inclusions (FIs) in quartz were identified as four types: PC-type (pure CO2), C1-type (CO2-bearing), C2-type (CO2-rich), and W-type (aqueous two-phase). Raman spectroscopy analysis revealed that the vapor components of the FIs predominantly comprised CO2 with minor quantities of CH4 in stages I–II. Stages I and II encompassed four types of FIs with homogenisation temperature ranging from 264 to 332 °C and 213 to 292 °C and salinity spanning from 4.7 to 11.2 wt% and 1.8 to 11.6 wt%, respectively. Stage III exclusively contained W-type FIs with homogenisation temperature ranging from 152 to 215 °C and salinity spanning from 1.4 to 6.4 wt%. H-O isotopic values (δD = −84 to −79.6‰, δ18OH2O = 6.2 to 6.4‰ in stage I and δD = −96.4 to −90.4‰, δ18OH2O = 2.8 to 4.4‰ in stage II) and microthermometric data indicated that the ore-forming fluids are initially from a magmatic source, with later meteoric water input. Low C isotopic data from CO2 in FIs in quartz (−24.4 to −24.3‰ in stage I and −23.7 to −22.6‰ in stage II) indicated an organic carbon source. Ore precipitation is mainly attributable to fluid immiscibility. S-Pb isotopic data (δ34S = −3.5 to −1.6‰; 206Pb/204Pb = 18.325–18.362, 207Pb/204Pb = 15.523–5.562, 208Pb/204Pb = 38.064–38.221) revealed that ore metals primarily originated from magma. Based on this research, the origin of the Batailing Au deposit is of the mesothermal magmatic–hydrothermal lode type. Full article
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25 pages, 7593 KiB  
Concept Paper
The Perception of Eros and the Cinema Audience Experience in Cádiz (Spain)
by Inmaculada Rodríguez-Cunill, Juan José Domínguez-López and Sonia Carlos-García
Societies 2024, 14(7), 96; https://doi.org/10.3390/soc14070096 - 21 Jun 2024
Viewed by 2269
Abstract
The perception of the concept of Eros has evolved through shared cinematic experiences, to the point of shaping collective imagery in Cadiz, Spain. This city is known for its creativity and an extraordinary amount of performances during the period of carnival, and is [...] Read more.
The perception of the concept of Eros has evolved through shared cinematic experiences, to the point of shaping collective imagery in Cadiz, Spain. This city is known for its creativity and an extraordinary amount of performances during the period of carnival, and is represented annually by anonymous citizens. The research method employed consisted of an exhaustive analysis of bibliographic, press, and archival references on audience behavior from the introduction of the cinematograph to the present day. The authors have designed a table that organizes the emergence of movie theaters in the city and completed the background information, delving into the historical, geographical, and idiosyncratic factors that have contributed to collective creativity in the city. From there, we analyzed the evolution of the concept of Eros through the perspectives of Byung Chul Han and Georges Bataille. As a result, we recovered the value of projection interruptions in the analog environment as an opportunity for collective interaction, confronting them with the demands of technological perfection. We demonstrated the resilience of the analog through new experiences that show the evolution of the need for collective contact. Future studies will focus on other contexts, such as supermarkets and terraces, to contribute to a broader understanding of urban spaces, social cohesion, and perceptions of Eros. Full article
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14 pages, 2198 KiB  
Article
CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in TCF3::PBX1 ALL
by Angela Gutierrez-Camino, Maxime Caron, Chantal Richer, Claire Fuchs, Unai Illarregi, Lucas Poncelet, Pascal St-Onge, Alain R. Bataille, Pascal Tremblay-Dauphinais, Elixabet Lopez-Lopez, Mireia Camos, Manuel Ramirez-Orellana, Itziar Astigarraga, Éric Lécuyer, Guillaume Bourque, Idoia Martin-Guerrero and Daniel Sinnett
Int. J. Mol. Sci. 2024, 25(3), 1477; https://doi.org/10.3390/ijms25031477 - 25 Jan 2024
Cited by 1 | Viewed by 3098
Abstract
Childhood B-cell acute lymphoblastic leukemia (B-ALL) is a heterogeneous disease comprising multiple molecular subgroups with subtype-specific expression profiles. Recently, a new type of ncRNA, termed circular RNA (circRNA), has emerged as a promising biomarker in cancer, but little is known about their role [...] Read more.
Childhood B-cell acute lymphoblastic leukemia (B-ALL) is a heterogeneous disease comprising multiple molecular subgroups with subtype-specific expression profiles. Recently, a new type of ncRNA, termed circular RNA (circRNA), has emerged as a promising biomarker in cancer, but little is known about their role in childhood B-ALL. Here, through RNA-seq analysis in 105 childhood B-ALL patients comprising six genetic subtypes and seven B-cell controls from two independent cohorts we demonstrated that circRNAs properly stratified B-ALL subtypes. By differential expression analysis of each subtype vs. controls, 156 overexpressed and 134 underexpressed circRNAs were identified consistently in at least one subtype, most of them with subtype-specific expression. TCF3::PBX1 subtype was the one with the highest number of unique and overexpressed circRNAs, and the circRNA signature could effectively discriminate new patients with TCF3::PBX1 subtype from others. Our results indicated that NUDT21, an RNA-binding protein (RBP) involved in circRNA biogenesis, may contribute to this circRNA enrichment in TCF3::PBX1 ALL. Further functional characterization using the CRISPR-Cas13d system demonstrated that circBARD1, overexpressed in TCF3::PBX1 patients and regulated by NUDT21, might be involved in leukemogenesis through the activation of p38 via hsa-miR-153-5p. Our results suggest that circRNAs could play a role in the pathogenesis of childhood B-ALL. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
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21 pages, 661 KiB  
Review
Current Evidence for Immune Checkpoint Inhibition in Advanced Hepatocellular Carcinoma
by Victoria Foy, Mairéad G. McNamara, Juan W. Valle, Angela Lamarca, Julien Edeline and Richard A. Hubner
Curr. Oncol. 2023, 30(9), 8665-8685; https://doi.org/10.3390/curroncol30090628 - 21 Sep 2023
Cited by 1 | Viewed by 3147
Abstract
The treatment of advanced unresectable HCC (aHCC) remains a clinical challenge, with limited therapeutic options and poor prognosis. The results of IMbrave150 and HIMALAYA have changed the treatment paradigm for HCC and established immune checkpoint inhibition (ICI), either combined with anti-angiogenic therapy or [...] Read more.
The treatment of advanced unresectable HCC (aHCC) remains a clinical challenge, with limited therapeutic options and poor prognosis. The results of IMbrave150 and HIMALAYA have changed the treatment paradigm for HCC and established immune checkpoint inhibition (ICI), either combined with anti-angiogenic therapy or dual ICI, as preferred first-line therapy for eligible patients with aHCC. Numerous other combination regimens involving ICI are under investigation with the aim of improving the tumour response and survival of patients with all stages of HCC. This review will explore the current evidence for ICI in patients with advanced HCC and discuss future directions, including the unmet clinical need for predictive biomarkers to facilitate patient selection, the effects of cirrhosis aetiology on response to ICI, and the safety of its use in patients with impaired liver function. Full article
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10 pages, 699 KiB  
Article
Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer
by Edith Borcoman, Elizabeth Santana dos Santos, Catherine Genestie, Patricia Pautier, Ludovic Lacroix, Sandrine M. Caputo, Odile Cabaret, Marine Guillaud-Bataille, Judith Michels, Aurelie Auguste, Alexandra Leary and Etienne Rouleau
Int. J. Mol. Sci. 2023, 24(14), 11570; https://doi.org/10.3390/ijms241411570 - 18 Jul 2023
Cited by 3 | Viewed by 2302
Abstract
Somatic/germline BRCA1/2 mutations (m)/(likely) pathogenic variants (PV) (s/gBRCAm) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic TP53m, combined tumor-based BRCA1/2 (tBRCA) and TP53 mutation [...] Read more.
Somatic/germline BRCA1/2 mutations (m)/(likely) pathogenic variants (PV) (s/gBRCAm) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic TP53m, combined tumor-based BRCA1/2 (tBRCA) and TP53 mutation testing (tBRCA/TP53m) may improve the quality of results in somatic BRCAm identification and interpretation of the ‘second hit’ event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent tBRCA/TP53m testing. The ratio of allelic fractions (AFs) for tBRCA/TP53m was calculated to estimate the proportion of cells carrying BRCAm and to infer LOH. Among the 142/237 gBRCA results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) gBRCA1/2m. Among the 195 contributive tumor samples, 43 DEL of tBRCAm (22.1%) were identified (23 gBRCAm and 20 sBRCAm) with LOH identified in 37/41 conclusive samples. The median AF of TP53m was 0.52 (0.01–0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both BRCA1/2m and TP53m, thus reidentifying them as sBRCA1/2m. Combined tBRCA/TP53m testing is rapid, sensitive, and identifies somatic and germline BRCA1/2m. AF TP53m is essential for interpreting sBRCA1/2m in low-cellularity samples and provides indirect evidence for LOH as the ‘second hit’ of BRCA1/2-related tumorigenesis. Full article
(This article belongs to the Special Issue Advances in Gynecological Cancers 2.0)
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11 pages, 709 KiB  
Perspective
The Ins and Outs of Endosteal Niche Disruption in the Bone Marrow: Relevance for Myeloma Oncogenesis
by Jean-Pascal Capp and Régis Bataille
Biology 2023, 12(7), 990; https://doi.org/10.3390/biology12070990 - 12 Jul 2023
Cited by 3 | Viewed by 1936
Abstract
Multiple Myeloma (MM) and its preexisting stage, termed Monoclonal Gammopathy of Undetermined Significance (MGUS), have long been considered mainly as genomic diseases. However, the bone changes observed in both conditions have led to a reassessment of the role of the bone microenvironment, mainly [...] Read more.
Multiple Myeloma (MM) and its preexisting stage, termed Monoclonal Gammopathy of Undetermined Significance (MGUS), have long been considered mainly as genomic diseases. However, the bone changes observed in both conditions have led to a reassessment of the role of the bone microenvironment, mainly the endosteal niche in their genesis. Here, we consider the disruption of the endosteal niche in the bone marrow, that is, the shift of the endosteal niche from an osteoblastic to an osteoclastic profile produced by bone senescence and inflammaging, as the key element. Thus, this disrupted endosteal niche is proposed to represent the permissive microenvironment necessary not only for the emergence of MM from MGUS but also for the emergence and maintenance of MGUS. Moreover, the excess of osteoclasts would favor the presentation of antigens (Ag) into the endosteal niche because osteoclasts are Ag-presenting cells. As such, they could significantly stimulate the presentation of some specific Ag and the clonal expansion of the stimulated cells as well as favor the expansion of such selected clones because osteoclasts are immunosuppressive. We also discuss this scenario in the Gaucher disease, in which the high incidence of MGUS and MM makes it a good model both at the bone level and the immunological level. Finally, we envisage that this endosteal niche disruption would increase the stochasticity (epigenetic and genetic instability) in the selected clones, according to our Tissue Disruption-induced cell Stochasticity (TiDiS) theory. Full article
(This article belongs to the Section Medical Biology)
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14 pages, 1291 KiB  
Article
Third-Line Palliative Systemic Therapy for Advanced Biliary Tract Cancer: Multicentre Review of Patterns of Care and Outcomes
by Simon Gray, Octave Letissier, Constance d’Abrigeon, Dinakshi Shah, Stephen Wardell, Olusola Faluyi, Angela Lamarca, Richard A. Hubner, Julien Edeline, Juan W. Valle and Mairéad G. McNamara
Cancers 2023, 15(11), 3047; https://doi.org/10.3390/cancers15113047 - 3 Jun 2023
Cited by 2 | Viewed by 2988
Abstract
Phase 3 trials have established standard first-line (1L) and 2L systemic therapy options for patients with advanced biliary cancer (ABC). However, a standard 3L treatment remains undefined. Clinical practice and outcomes for 3L systemic therapy in patients with ABC were therefore evaluated from [...] Read more.
Phase 3 trials have established standard first-line (1L) and 2L systemic therapy options for patients with advanced biliary cancer (ABC). However, a standard 3L treatment remains undefined. Clinical practice and outcomes for 3L systemic therapy in patients with ABC were therefore evaluated from three academic centres. Included patients were identified using institutional registries; demographics, staging, treatment history, and clinical outcomes were collected. Kaplan–Meier methods were used to assess progression-free survival (PFS) and overall survival (OS). Ninety-seven patients, treated between 2006 and 2022, were included; 61.9% had intrahepatic cholangiocarcinoma. At the time of analysis, there had been 91 deaths. Median PFS from initiating 3L palliative systemic therapy (mPFS3) was 3.1 months (95%CI 2.0–4.1), while mOS3 was 6.4 months (95%CI 5.5–7.3); mOS1 was 26.9 months (95%CI 23.6–30.2). Among patients with a therapy-targeted molecular aberration (10.3%; n = 10; all received in 3L), mOS3 was significantly improved versus all other included patients (12.5 vs. 5.9 months; p = 0.02). No differences in OS1 were demonstrated between anatomical subtypes. Fourth-line systemic therapy was received by 19.6% of patients (n = 19). This international multicentre analysis documents systemic therapy use in this select patient group, and provides a benchmark of outcomes for future trial design. Full article
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12 pages, 1241 KiB  
Article
Post-Marketing Use of Teduglutide in a Large Cohort of Adults with Short Bowel Syndrome-Associated Chronic Intestinal Failure: Evolution and Outcomes
by Brune de Dreuille, Alexandre Nuzzo, Julie Bataille, Charlotte Mailhat, Lore Billiauws, Maude Le Gall and Francisca Joly
Nutrients 2023, 15(11), 2448; https://doi.org/10.3390/nu15112448 - 24 May 2023
Cited by 12 | Viewed by 2838
Abstract
Teduglutide, a GLP-2 analogue, has been available in France since 2015 to treat short-bowel-syndrome (SBS)-associated chronic intestinal failure (CIF) but it remains very expensive. No real-life data on the number of potential candidates are available. The aim of this real-life study was to [...] Read more.
Teduglutide, a GLP-2 analogue, has been available in France since 2015 to treat short-bowel-syndrome (SBS)-associated chronic intestinal failure (CIF) but it remains very expensive. No real-life data on the number of potential candidates are available. The aim of this real-life study was to assess teduglutide initiation and outcomes in SBS-CIF patients. All SBS-CIF patients cared for in an expert home parenteral support (PS) center between 2015 and 2020 were retrospectively included. Patients were divided into two subpopulations: prevalent patients, already cared for in the center before 2015, and incident patients, whose follow-up started between 2015 and 2020. A total of 331 SBS-CIF patients were included in the study (156 prevalent and 175 incident patients). Teduglutide was initiated in 56 patients (16.9% of the cohort); in 27.9% of prevalent patients and in 8.0% of incident patients, with a mean annual rate of 4.3% and 2.5%, respectively. Teduglutide allowed a reduction in the PS volume by 60% (IQR: 40–100), with a significantly higher reduction in incident versus prevalent patients (p = 0.02). The two- and five-year treatment retention rates were 82% and 64%. Among untreated patients, 50 (18.2%) were considered ineligible for teduglutide for non-medical reasons. More than 25% of prevalent SBS patients were treated with teduglutide compared to 8% of incident patients. The treatment retention rate was >80% at 2 years, which could be explained by a careful selection of patients. Furthermore, this real-life study confirmed the long-term efficacy of teduglutide and showed a better response to teduglutide in incident patients, suggesting a benefit in early treatment. Full article
(This article belongs to the Special Issue Recent Insights/Advances in Intestinal Failure Management)
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21 pages, 3643 KiB  
Article
Evaluation of External Trigeminal Nerve Stimulation to Prevent Cerebral Vasospasm after Subarachnoid Hemorrhage Due to Aneurysmal Rupture: A Randomized, Double-Blind Proof-of-Concept Pilot Trial (TRIVASOSTIM Study)
by Philippe Rigoard, Maxime Billot, Maarten Moens, Lisa Goudman, Hassan El-Hajj, Pierre Ingrand, Amine Ounajim, Manuel Roulaud, Philippe Page, Etienne Babin, Mohamed Et Talby, Jonathan Dany, Simona Johnson, Benoit Bataille, Romain David and Konstantin V. Slavin
Int. J. Environ. Res. Public Health 2023, 20(10), 5836; https://doi.org/10.3390/ijerph20105836 - 16 May 2023
Cited by 4 | Viewed by 3093
Abstract
Cerebral vasospasm remains the most frequent and devastating complication after subarachnoid aneurysmal hemorrhage because of secondary cerebral ischemia and its sequelae. The underlying pathophysiology involves vasodilator peptide release (such as CGRP) and nitric oxide depletion at the level of the precapillary sphincters of [...] Read more.
Cerebral vasospasm remains the most frequent and devastating complication after subarachnoid aneurysmal hemorrhage because of secondary cerebral ischemia and its sequelae. The underlying pathophysiology involves vasodilator peptide release (such as CGRP) and nitric oxide depletion at the level of the precapillary sphincters of the cerebral (internal carotid artery network) and dural (external carotid artery network) arteries, which are both innervated by craniofacial autonomic afferents and tightly connected to the trigeminal nerve and trigemino-cervical nucleus complex. We hypothesized that trigeminal nerve modulation could influence the cerebral flow of this vascular network through a sympatholytic effect and decrease the occurrence of vasospasm and its consequences. We conducted a prospective double-blind, randomized controlled pilot trial to compare the effect of 10 days of transcutaneous electrical trigeminal nerve stimulation vs. sham stimulation on cerebral infarction occurrence at 3 months. Sixty patients treated for aneurysmal SAH (World Federation of Neurosurgical Societies scale between 1 and 4) were included. We compared the radiological incidence of delayed cerebral ischemia (DCI) on magnetic resonance imaging (MRI) at 3 months in moderate and severe vasospasm patients receiving trigeminal nerve stimulation (TNS group) vs. sham stimulation (sham group). Our primary endpoint (the infarction rate at the 3-month follow-up) did not significantly differ between the two groups (p = 0.99). Vasospasm-related infarctions were present in seven patients (23%) in the TNS group and eight patients (27%) in the sham group. Ultimately, we were not able to show that TNS can decrease the rate of cerebral infarction secondary to vasospasm occurrence. As a result, it would be premature to promote trigeminal system neurostimulation in this context. This concept should be the subject of further research. Full article
(This article belongs to the Special Issue Research on Pain Measurements and Pain Outcome Variables)
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11 pages, 285 KiB  
Article
From Havana to Cádiz in the Imaginary of Women Writers of the Last Decades
by María del Mar López-Cabrales and Inmaculada Rodríguez-Cunill
Literature 2023, 3(2), 242-252; https://doi.org/10.3390/literature3020017 - 15 May 2023
Cited by 1 | Viewed by 2022
Abstract
In this essay, we intend to demonstrate how the cities of Havana and Cádiz became mutable literary subjects that accompany the female characters of the narratives of female writers of the past decades from Havana (Anna Lidia Vega Serova, Ena Lucía Portela, and [...] Read more.
In this essay, we intend to demonstrate how the cities of Havana and Cádiz became mutable literary subjects that accompany the female characters of the narratives of female writers of the past decades from Havana (Anna Lidia Vega Serova, Ena Lucía Portela, and Mylene Fernández Pintado) and Cádiz (Ana Rossetti and Pilar Paz Pasamar). The ironic and delusional visions of a ruined life due to the special period, economic crisis, and political xenophobia in Cádiz will be illustrated by Cuban-Spanish mapping of the analyzed authors’ works. Our hypothesis stems from the idea that there is a clear relation between the representation of the city and political, cultural, and patriarchal transgression that is quoted in these texts (Bataille), which relates to the experience of scarcity/poverty lived on both sides of the Atlantic Ocean. Our bibliographic search has focused on the literary expression of the experience of these cities from the point of view of female writers and protagonists. We concluded with a universal understanding of the experience of the space marked by literature and the gaze of women. Full article
11 pages, 445 KiB  
Article
TIcagrelor in Rotational Atherectomy to Reduce TROPonin Enhancement: The TIRATROP Study, A Randomized Controlled Trial
by Thibault Lhermusier, Pascal Motreff, Vincent Bataille, Guillaume Cayla, Bruno Farah, Jerome Roncalli, Meyer Elbaz, Nicolas Boudou, Fransisco Campello-Parada, Frederic Bouisset, Geraud Souteyrand, Emilie Berard, Vanina Bongard and Didier Carrie
J. Clin. Med. 2023, 12(4), 1445; https://doi.org/10.3390/jcm12041445 - 11 Feb 2023
Cited by 7 | Viewed by 2079
Abstract
Background: Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin [...] Read more.
Background: Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin release. Methods: TIRATROP (TIcagrelor in Rotational Atherectomy to reduce TROPonin enhancement) is a multicenter double-blind randomized controlled trial that included 180 patients with severe calcified lesions requiring RA who received either clopidogrel (300 mg loading dose, then 75 mg/d) or ticagrelor (loading dose 180 mg then 90 mg twice daily). Blood samples were collected at the beginning (T0), and 6, 12, 18, 24 and 36 h after the procedure. Primary end point was troponin release within the first 24 h using area under the curve analysis (troponin level as a function of time). Results: The mean age of patients was 76 ± 10 years, 35% had diabetes. RA was used to treat 1, 2 or 3 calcified lesions in 72%, 23% and 5% of patients, respectively. Troponin release within the first 24 h was similar in both the ticagrelor (adjusted mean ±SD of ln AUC 8.85 ± 0.33) and the clopidogrel (8.77 ± 0.34, p = 0.60) arms. Independent predictors for troponin enhancement were acute coronary syndrome presentation, renal failure, elevated C-Reactive protein and multiple lesions treated with RA. Conclusion: Troponin release did not differ among treatment arms. Our results suggest that greater platelet inhibition does not affect periprocedural myocardial necrosis in the setting of RA. Full article
(This article belongs to the Special Issue Coronary Artery Disease Interventions)
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