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Competing Interests: Conflicts of interest None disclosed.

In the search of new cymantrenyl- and ferrocenyl-sulfonamides as potencial inhibitors of human carbonic anhydrases (hCAs), four compounds based on N-ethyl or N-methyl benzenesulfonamide units have been obtained. These cymantrenyl (1a-b) and ferrocenyl (2a-b) derivatives were prepared by the reaction between aminobenzene sulfonamides ([NH 2 -(CH 2 ) n -(C 6 H 4 )-SO 2 -NH 2 )], where n = 1, 2) with cymantrenyl sulfonyl chloride (P1) or ferrocenyl sulfonyl chloride (P2), respectively. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. In the solid state, the molecular structures of compounds 1a, 1b, and 2b were determined by single-crystal X-ray diffraction. Biological evaluation as carbonic anhydrases inhibitors were carried out and showed derivatives 1b y 2b present a higher inhibition than the drug control for the Human Carbonic Anhydrase (hCA) II and IX isoforms (K I  = 7.3 nM and 5.8 nM, respectively) and behave as selective inhibition for hCA II isoform. Finally, the docking studies confirmed they share the same binding site and interactions as the known inhibitors acetazolamide (AAZ) and agree with biological studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodrigo Arancibia reports financial support was provided by National Agency for Research and Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To assess the acceptance and intention to use physiological sensor shirt among older patients in healthcare, as well as to identify the factors that encourage a positive attitude towards its adoption., Methods: Cross-sectional study using questionnaires addressed to patients between 60 and 85years of age, administered via face-to-face interviews to determine intention to use a shirt with physiological sensors. The extended version of the Technology Acceptance Model (TAM) questionnaire was used in conjunction with administration of the quality of life and perceived stress scales., Results: Forty-eight patients participated in the study, 54.2% were male with a mean age of 70.5years. The mean scores for attitude towards use and intention to use were 3.9 (SD: 0.8) and 3.3 (SD: 0.8), respectively, out of a maximum of 5. The willingness to use the device was positive in 72.9% of patients The patients intending to use wearable technology (n=35) scored significantly higher than those unwilling to wear the shirt (n=13) on perceived ubiquity (P=.031), perceived ease of use (P=.002), and perceived utility (P=.007)., Conclusions: In a sample of independent older adults from the healthcare sector, a high willingness to use a shirt with physiological sensors was found. Through the TAM questionnaire, ubiquity, perceived ease of use, and perceived usefulness were identified as key factors predisposing its adoption., (Copyright © 2024 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

We present the case of a 68-year-old female who presented with a substantial cyclodialysis after phacoemulsification identified by anterior segment optical coherence tomography and ultrasound biomicroscopy. Gonioscopy is challenging because of its shallow anterior chamber. Due to lack of response to topical steroids and refusal by the patient for surgical treatment, topical steroids were tapered, and cycloplegic was initiated. After two weeks, the cyclodialysis cleft was closed on optical coherence tomography persisting residual subchoroidal fluid, topical treatment was mantained. Despite of this, visual acuity and hypotony were restored. Finally at 2 months visit subchoroidal fluid was reabsorbed and patient was discharged. Clinics should consider the possibility of cyclodialysis in cases of unjustified hypotony during postoperative period. In addition, we recommend performing anterior segment imaging which includes ultrasound biomicroscopy and optical coherence tomography, when the evaluation of angular structures is unfeasible. Finally, we propose medical management for severe cyclodialysis as the first option considering anti-inflammatory drugs could perpetrate the separation between scleral spur and ciliary muscle., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To assess the impact of below-benchmark (95%-100%) donor-oocyte survival rates on vitrification/warming in the laboratory and clinical outcomes of recipient cycles., Design: Retrospective cohort study., Setting: A network of European private in vitro fertilization units., Patient(s): We analyzed 12,690 vitrified-warmed donor-oocyte recipient cycles performed from 2018-2022., Intervention(s): All cycles analyzed used exclusively vitrified/warmed donor oocytes. The cycles were grouped according to the survival rate experienced: benchmark 95%-100%; competence 85%-95%; below competence 70%-85%; poor 50%-70%; and very poor <50%., Main Outcome Measure(s): The primary endpoint of the study was the total usable blastocyst rate per 2 pronuclear (2PN) zygote. Secondary endpoints were the fertilization rate, the live birth rate after the first single blastocyst transfer, and the cumulative live birth rate., Result(s): The mean number of warmed oocytes per intracytoplasmic sperm injection (ICSI) cycle was 11.4 ± 3.2, with a mean survival rate of 89.1%. More oocytes per cycle were consumed in the lower survival groups, yet the total number of oocytes available for ICSI was smaller in the below-competence, poor, and very poor survival groups. The total usable blastocyst rate was lower in the lower survival groups (benchmark: 48.9%; competence: 47.0%, below competence: 46.0%; poor: 43.6%; and very poor: 43.6%), as well as the fertilization rates (benchmark: 76.8%; competence: 76.6%, below competence: 75.6%; poor: 74.7%; and very poor:75.5%). The adjusted relative risk (aRR) of live birth rate of the first embryo transferred was equal to the benchmark survival group in all the lower survival groups (benchmark: 40.9%; competence: aRR = 0.986, 95% confidence interval [CI]: 0.931-1.045; below-competence: aRR = 0.992, 95% CI: 0.929-1.059; poor: aRR = 1.103, 95% CI: 1.009-1.207; and very poor: aRR = 1.169, 95% CI: 0.963-1.419). The cumulative live birth rate decreased in lower survival groups compared with benchmark survival (benchmark: 79.2%; competence: aRR = 0.988, 95% CI: 0.961-1.015; below competence: aRR = 0.911, 95% CI: 0.880-0.944; poor: aRR = 0.802, 95% CI: 0.757-0.851; and very poor: aRR = 0.793, 95% CI: 0.693-0.907). The lower cumulative rates maintained in a subanalysis with equal metaphase-II available for ICSI (benchmark: 69.5%; competence: aRR = 0.909, 95% CI: 0.827-1.000; below competence: aRR = 0.942, 95% CI: 0.848-1.046; poor: aRR = 0.833, 95% CI: 0.7386-0.941; and very poor: aRR = 0.873, 95% CI: 0.695-1.097) CONCLUSIONS: Lower donor-oocyte cryo-survival rates have a moderate negative impact on the blastocyst utilization rate per 2PN zygote, fertilization rate, and the cumulative live birth rates of a donation cycle, even after adjusting for equal metaphase-II oocytes available for ICSI. Nonetheless, the surviving oocytes of a cohort seem to maintain a high competence level, with very similar laboratory outcomes, irrespective of the cohort's survival rates, as well as equal implantation potential of the resulting blastocysts., Competing Interests: Declaration of Interests M.G. reports honoraria from Merck GmBH outside the submitted work. I.G. has nothing to disclose. J.R. has nothing to disclose. A.P.S. has nothing to disclose. N.G. has nothing to disclose. J.L.M. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Mortality among people with dependency to perform basic activities of daily living (ADL) is higher than that of non-dependent people of the same age. Understanding the evolutionary course and factors involved in non-institutionalized ADL dependency, including the influence of the family structure that supports this population, would contribute to improved health planning., Methods: A longitudinal study carried out in the ADL-dependent population of the Orcasitas neighborhood, Madrid (Spain), between June 2020, when the nationwide COVID-19 lockdown ended, and June 2023. A total of 127 patients participated in the study, 78.7% of whom were women and 21.3% were men. Risk analysis was performed via odds ratios (OR) and hazard ratios (HR). Survival analysis was performed using Cox regression., Results: A total of 54.33% of the ADL-dependent persons did not live with their adult children and 45.67% did, being associated living independently with economic capacity and the married marital status but not with the dependency level. In women, being married increased the probability of living independently of their adult children (OR = 12.632; 95% CI = 3.312-48.178). Loss of mobility (OR = 0.398; 95% CI = 0.186-0.853), economic capacity of the dependent (HR = 0.596; 95% CI = 0.459-0.774), and living independently and having better economic capacity (HR = 0.471; 95% CI = 0.234-0.935) were associated with 3-year survival. Those who lived with their adult children had a worse autonomy profile and higher mortality (HR = 1.473; 95% CI = 1.072-2.024). Not being employed, not being married, and not owning a home were significantly associated with being an essential family caregiver. Caregivers were mostly women (OR = 1.794; 95% CI = 1.011-3.182)., Conclusion: Among ADL-dependent persons, economic capacity influenced the ability to living independently and affected survival after 3 years. Loss of mobility (wheelchair use) was a predictor of mortality. Social inequalities promote that adult children end up as essential family caregivers. This generates reverse dependency and maintains a vulnerability that is transmitted from generation to generation, perpetuating social and gender inequalities. Dependent parent care in this cohort maintained an archaic pattern in which the eldest daughter cared for her parents. This study made it possible to show that ADL dependence is accompanied by complex interrelationships that must be considered in socio-health planning., Competing Interests: NS was employed by Senex. ES was employed by Frezent Biological Solutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martín Moreno, Martínez Sanz, Martín Fernández, Sánchez Rodríguez, Sánchez González, Herranz Hernando, Fernández Gallardo, Recuero Vázquez, Benítez Calderón, Sevillano Fuentes, Pérez Rico, Calderón Jiménez, Guerra Maroto, Alonso Samperiz and León Saiz.)

Objectives: To show donation data, number of keratoplasties and the changes in transplant indications and techniques that occurred in Andalusia in the period from 2013 to 2022., Materials and Methods: The present work is a retrospective and descriptive study that included all keratoplasties performed between January 2013 and December 2022 in Andalusia, as well as the evolution of the cornea donation and transplant activity of the public and private hospitals pertaining to the waiting list management system of the Public Health System of Andalusia. Transplants performed in private centers with corneas from outside Andalusia were excluded., Results: Cornea donation activity in Andalusia in the decade 2013-2022 has experienced a growth of more than 126%, while overall transplant activity has increased by 157% in public hospitals. Penetrating keratoplasty has decreased from 83% in 2013 to 43% in 2022, while lamellar techniques have increased from 17% to 57% in this same period. Since 2018, more lamellar transplants are performed than penetrating transplants. Regarding indications, endothelial conditions already represent the first cause of transplantation. In 2022 alone, the public Andalusian Eye Banks evaluated 1,054 corneas and prepared 281 endothelial grafts., Conclusion: In the decade from 2013 to 2022 in Andalusia there has been an increase in donation activity and the number of keratoplasties. The public Eye Banks implementation in this period has played a key role in the widespread adoption of lamellar keratoplasty techniques and has enabled the transition to perform a greater number of lamellar keratoplasties compared to penetrating keratoplasty., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

The error-related negativity (ERN) is an event-related potential that is observed after the commission of an error and is hypothesized to index threat sensitivity. The ERN is associated with multiple psychiatric disorders, but it is unclear if similar results are due to higher-order dimensions of psychopathology. When errors are punished, the ERN is further enhanced, which might better isolate threat sensitivity. However, few studies have examined whether psychopathology is associated with punishment enhancement of the ERN. In a clinical sample of 170 adults, the present study examined the association between pathological personality domains and predictable vs. unpredictable punishment-enhanced ERN. Results indicated that the ERN was enhanced when errors were punished compared to not punished. Greater negative emotionality was associated with a greater predictable punishment-enhanced ERN, while greater disinhibition was associated with smaller predictable punishment-enhanced ERN. The study suggests that higher-order pathological personality domains demonstrate discriminate relationships with punishment-enhanced error-related brain activity., Competing Interests: Declaration of competing interest The authors declare that there were no conflicts of interest with respect to the authorship or the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Point-of-care ultrasonography (POCUS) has rapidly evolved from a niche technology to an indispensable tool across medical specialties, including nephrology. This evolution is driven by advancements in technology and the visionary efforts of clinicians in emergency medicine and beyond. Recognizing its potential, medical schools are increasingly integrating POCUS into training curricula, emphasizing its role in enhancing diagnostic accuracy and patient care. Despite these advancements, barriers such as limited faculty expertise and 'lack of' standardized guidelines hinder widespread adoption and regulation. The International Alliance for POCUS in Nephrology (IAPN), through this position statement, aims to guide nephrologists in harnessing the diagnostic power of POCUS responsibly and effectively. By outlining core competencies, recommending training modalities and advocating for robust quality assurance measures, we envision a future where POCUS enhances nephrology practice globally, ensuring optimal patient outcomes through informed, evidence-based decision-making. International collaboration and education are essential to overcome current challenges and realize the full potential of POCUS in nephrology and beyond., Competing Interests: S.A. is supported by ECHONous with a research grant in kind. The remainder of the authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Purpose: This study aims to evaluate the efficacy of admission contrast-enhanced CT scans in formulating strategies for performing early laparoscopic cholecystectomy in cases of acute gallstone pancreatitis., Methods: Patients diagnosed with acute gallstone pancreatitis underwent a CT scan upon admission (after at least 24 h from symptom onset) to confirm diagnosis and assess peripancreatic fluid, collections, gallstones, and common bile duct stones. Patients with mild acute gallstone pancreatitis, following the Atlanta classification and Baltazar score A or B, were identified as candidates for early cholecystectomy (within 72 h of admission)., Results: Within the analyzed period, 272 patients were diagnosed with mild acute gallstone pancreatitis according to the Atlanta Guidelines. A total of 33 patients (12.1%) were excluded: 17 (6.25%) due to SIRS, 10 (3.6%) due to local complications identified in CT (Balthazar D/E), and 6 (2.2%) due to severe comorbidities. Enhanced CT scans accurately detected gallstones, common bile duct stones, pancreatic enlargement, inflammation, pancreatic collections, and peripancreatic fluid. Among the cohort, 239 patients were selected for early laparoscopic cholecystectomy. Routine intraoperative cholangiogram was conducted in all cases, and where choledocholithiasis was present, successful treatment occurred through common bile duct exploration. Only one case required conversion from laparoscopic to open surgery. There were no observed severe complications or mortality., Conclusion: Admission CT scans are instrumental in identifying clinically stable patients with local tomographic complications that contraindicate early surgery. Patients meeting the criteria for mild acute gallstone pancreatitis, as per Atlanta guidelines, without SIRS or local complications (Baltazar D/E), can safely undergo early cholecystectomy within the initial 72 h of admission., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study assessed the incidence of postsurgical intraocular inflammation after cataract extraction by phacoemulsification and implantation with AcrySof IQ ReSTOR intraocular lenses (IOLs) produced using an updated manufacturing process. Incidence rates were compared with historical rates of postsurgical intraocular inflammation., Methods: This was a prospective, multicenter, post-approval study at 34 sites. Patients aged ≥22 years received a study lens in at least 1 eye. Postsurgical intraocular inflammation (aqueous cell grade ≥3+ within 14 days after surgery, aqueous cell ≥2+ at 14 to ≤60 days after surgery, or aqueous cell ≥1+ at >60 days) was assessed within a 180-day period after implantation. Rates of toxic anterior segment syndrome (TASS), acute postoperative endophthalmitis, chronic postoperative endophthalmitis, and uncategorized cases of postsurgical intraocular inflammation were assessed. Ocular adverse events (AEs) and ocular adverse device effects (ADEs) were evaluated. Historical rates of postsurgical intraocular inflammation were determined from the 2011-2013 Medicare Limited Data Set files (a 5% sample of the Medicare data set representative of patients aged ≥65 years)., Results: Final safety analysis set included 3357 eyes (1792 patients; mean age, 68.6 ± 7.9 years). Postsurgical intraocular inflammation (any type) rate was 5.1 per 1000 attempted IOL implants (95% CI, 2.95, 8.10). TASS, acute postoperative endophthalmitis, and uncategorized inflammation rates were 0.6 (95% CI, 0.07, 2.15), 0.3 (95% CI, 0.01, 1.66), and 4.2 (95% CI, 2.28, 6.99) per 1000 attempted IOL implants, respectively. There were no events of chronic postoperative endophthalmitis. Ocular AEs and ADEs were reported in 17% and 1.5% of eyes, respectively. Most common ADEs were halo (0.63%) and glare (0.51%). The historical postsurgical inflammation rate from 221,519 cataract procedures was 10.3/1000 cataract surgeries, and the endophthalmitis rate was 1.2/1000 surgeries., Conclusion: The updated IOL manufacturing process resulted in postoperative intraocular inflammation rates that were substantially lower than the historic rate., Competing Interests: James Paauw received research support from Alcon. Michael Caplan received research support and consulting fees from Alcon. Mark Gallardo received research support and consulting fees and was a speaker for Alcon. Kristi Rushin is an employee of Alcon. Jeff Horn received research support from Alcon and was a consultant and speaker for Alcon. The authors report no other conflicts of interest in this work., (© 2024 Paauw et al.)

Background: Prolonged confinement can lead to personal deterioration at various levels. We studied this phenomenon during the nationwide COVID-19 lockdown in a functionally dependent population of the Orcasitas neighborhood of Madrid, Spain, by measuring their ability to perform basic activities of daily living and their mortality rate., Methods: A total of 127 patients were included in the Orcasitas cohort. Of this cohort, 78.7% were female, 21.3% were male, and their mean age was 86 years. All participants had a Barthel index of ≤ 60. Changes from pre- to post-confinement and 3 years afterward were analyzed, and the effect of these changes on survival was assessed (2020-2023)., Results: The post-confinement functional assessment showed significant improvement in independence over pre-confinement for both the Barthel score ( t = -5.823; p < 0.001) and the classification level ( z = -2.988; p < 0.003). This improvement progressively disappeared in the following 3 years, and 40.9% of the patients in this cohort died during this period. These outcomes were associated with the Barthel index ( z = -3.646; p < 0.001) and the level of dependence (hazard ratio 2.227; CI 1.514-3.276). Higher mortality was observed among men (HR 1.745; CI 1.045-2.915) and those with severe dependence (HR 2.169; CI 1.469-3.201). Setting the cutoff point of the Barthel index at 40 provided the best detection of the risk of death associated with dependence., Conclusions: Home confinement and the risk of death due to the COVID-19 pandemic awakened a form of resilience in the face of adversity among the population of functionally dependent adults. The Barthel index is a good predictor of medium- and long-term mortality and is a useful method for detecting populations at risk in health planning. A cutoff score of 40 is useful for this purpose. To a certain extent, the non-institutionalized dependent population is an invisible population. Future studies should analyze the causes of the high mortality observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martín Moreno, Martínez Sanz, Fernández Gallardo, Martín Fernández, Benítez Calderón, Alonso Samperiz, Pérez Rico, Calderón Jiménez, Guerra Maroto, Sánchez Rodríguez, Sevillano Fuentes, Sánchez González, Recuero Vázquez, Herranz Hernando and León Saiz.)

Background/aim: Extracellular vesicle DNA (EV-DNA) has emerged as a novel biomarker for tumor mutation detection using liquid biopsies, exhibiting biological advantages compared to cell-free DNA (cfDNA). This study assessed the feasibility of EV-DNA and cfDNA extraction and sequencing in old serum samples of patients with breast cancer (BC)., Patients and Methods: A total of 28 serum samples of 27 patients with corresponding clinical information were collected between 1983 and 1991. EV-DNA was extracted using Exo-GAG kit (Nasabiotech) and cfDNA using QIAsymphony DSP Virus/Pathogen Midi Kit (Qiagen), respectively. Subsequently, 10 matched samples (EV-DNA n=5, cfDNA n=5) of five patients were subjected to sequencing using the Oncomine™ Breast cfDNA Research Assay v2 (Thermo Fisher Scientific)., Results: Samples were collected on median 1.9 years after primary diagnosis [interquartile range (IQR)=0.2-7.2]. Median follow-up was 9.5 years (IQR=5.2-14.2). Median age of serum samples was 36.1 years (IQR=34.5-37.3). EV-DNA and cfDNA were extracted from 100% (28/28) of the included samples. Both, DNA quantity and concentration were comparable between EV-DNA and cfDNA. Sequencing was successfully performed in 100% (10/10) of the included samples. Two matched analyses yielded equivalent results in EV-DNA and cfDNA (no mutations, n=1; PIK3CA mutation, n=1), whilst in two analyses, PIK3CA mutation was only found in cfDNA, and in one analysis, a TP53 mutation was only found in EV-DNA., Conclusion: EV-DNA extraction and sequencing in old serum samples of patients with BC is feasible and has the potential to address clinically relevant questions in longitudinal studies., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome is a rare condition characterized by clinical features of all three dermatologic conditions. The management of PASH syndrome is difficult, with no consensus on treatment guidelines. Since PASH syndrome can increase morbidity and adversely impact quality of life, better characterization of effective therapies is needed., Methods: A retrospective cohort study was conducted to identify all patients with pyoderma gangrenosum (PG) treated at The Ohio State University Wexner Medical Center between 2015 and 2021. PG diagnosis was confirmed via PARACELSUS score. Subsequent chart review identified eight patients with concomitant hidradenitis suppurativa (HS) and acne who were clinically diagnosed with PASH syndrome., Results: Eight patients were clinically diagnosed with PASH syndrome based on their clinical presentation at our institution. Seven patients had failed some type of medical therapy prior to presentation, including topical corticosteroids, oral corticosteroids, oral antibiotics, and biologics. One patient had also tried surgical drainage at an outside institution. Six patients were effectively treated with biologics, usually in combination with other therapies. One patient experienced improvement of her skin lesions after diagnosis and treatment of her underlying hematologic malignancy., Conclusions: Medical management with biologics in combination with corticosteroids and/or antibiotics was effective in the management of most patients. Diagnosis and treatment of an underlying condition should be prioritized in refractory cases. If workup is negative, surgical management may be considered. Further investigation with a greater number of patients is required to develop management guidelines for PASH syndrome., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: To explore the structural-functional loss relationship from optic-nerve-head- and macula-centred spectral-domain (SD) Optical Coherence Tomography (OCT) images in the full spectrum of glaucoma patients using deep-learning methods., Methods: A cohort comprising 5238 unique eyes classified as suspects or diagnosed with glaucoma was considered. All patients underwent ophthalmologic examination consisting of standard automated perimetry (SAP), macular OCT, and peri-papillary OCT on the same day. Deep learning models were trained to estimate G-pattern visual field (VF) mean deviation (MD) and cluster MD using retinal thickness maps from seven layers: retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), inner nuclear layer and outer plexiform layer (INL + OPL), outer nuclear layer (ONL), photoreceptors and retinal pigmented epithelium (PR + RPE), choriocapillaris and choroidal stroma (CC + CS), total retinal thickness (RT)., Results: The best performance on MD prediction is achieved by RNFL, GCL + IPL and RT layers, with R2 scores of 0.37, 0.33, and 0.31, respectively. Combining macular and peri-papillary scans outperforms single modality prediction, achieving an R2 value of 0.48. Cluster MD predictions show promising results, notably in central clusters, reaching an R2 of 0.56., Conclusions: The combination of multiple modalities, such as optic-nerve-head circular B-scans and retinal thickness maps from macular SD-OCT images, improves the performance of MD and cluster MD prediction. Our proposed model demonstrates the highest level of accuracy in predicting MD in the early-to-mid stages of glaucoma., Translational Relevance: Objective measures recorded with SD-OCT can optimize the number of visual field tests and improve individualized glaucoma care by adjusting VF testing frequency based on deep-learning estimates of functional damage.

Aim: To identify predictive variables and construct a predictive model along with a decision algorithm to identify nephrourological malformations (NUM) in children with febrile urinary tract infections (fUTI), enhancing the efficiency of imaging diagnostics., Methods: We performed a retrospective study of patients aged <16 years with fUTI at the Emergency Department with subsequent microbiological confirmation between 2014 and 2020. The follow-up period was at least 2 years. Patients were categorised into two groups: 'NUM' with previously known nephrourological anomalies or those diagnosed during the follow-up and 'Non-NUM' group., Results: Out of 836 eligible patients, 26.8% had underlying NUMs. The study identified six key risk factors: recurrent UTIs, non-Escherichia coli infection, moderate acute kidney injury, procalcitonin levels >2 μg/L, age <3 months at the first UTI and fUTIs beyond 24 months. These risk factors were used to develop a predictive model with an 80.7% accuracy rate and elaborate a NUM-score classifying patients into low, moderate and high-risk groups, with a 10%, 35% and 93% prevalence of NUM. We propose an algorithm for approaching imaging tests following a fUTI., Conclusion: Our predictive score may help physicians decide about imaging tests. However, prospective validation of the model will be necessary before its application in daily clinical practice., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: Voltage-gated calcium (Ca V ) channels play an essential role in maintaining calcium homeostasis and regulating numerous physiological processes in neurons. Therefore, dysregulation of calcium signaling is relevant in many neurological disorders, including Parkinson's disease (PD). This review aims to introduce the role of Ca V channels in PD and discuss some novel aspects of channel regulation and its impact on the molecular pathophysiology of the disease., Methods: an exhaustive search of the literature in the field was carried out using the PubMed database of The National Center for Biotechnology Information. Systematic searches were performed from the initial date of publication to May 2022., Results: Although α-synuclein aggregates are the main feature of PD, L-type calcium (Ca V 1) channels seem to play an essential role in the pathogenesis of PD. Changes in the functional expression of Ca V 1.3 channels alter Calcium homeostasis and contribute to the degeneration of dopaminergic neurons. Furthermore, recent studies suggest that Ca V channel trafficking towards the cell membrane depends on the activity of the ubiquitin-proteasome system (UPS). In PD, there is an increase in the expression of L-type channels associated with a decrease in the expression of Parkin, an E3 enzyme of the UPS. Therefore, a link between Parkin and Ca V channels could play a fundamental role in the pathogenesis of PD and, as such, could be a potentially attractive target for therapeutic intervention., Conclusion: The study of alterations in the functional expression of Ca V channels will provide a framework to understand better the neurodegenerative processes that occur in PD and a possible path toward identifying new therapeutic targets to treat this condition.

Allogeneic hematopoietic stem cell transplantation (aHSCT) can cure patients with otherwise fatal leukemias and lymphomas. However, the benefits of aHSCT are limited by graft-versus-host disease (GVHD). Minnelide, a water-soluble analog of triptolide, has demonstrated potent antiinflammatory and antitumor activity in several preclinical models and has proven both safe and efficacious in clinical trials for advanced gastrointestinal malignancies. Here, we tested the effectiveness of Minnelide in preventing acute GVHD as compared with posttransplant cyclophosphamide (PTCy). Strikingly, we found Minnelide improved survival, weight loss, and clinical scores in an MHC-mismatched model of aHSCT. These benefits were also apparent in minor MHC-matched aHSCT and xenogeneic HSCT models. Minnelide was comparable to PTCy in terms of survival, GVHD clinical score, and colonic length. Notably, in addition to decreased donor T cell infiltration early after aHSCT, several regulatory cell populations, including Tregs, ILC2s, and myeloid-derived stem cells in the colon were increased, which together may account for Minnelide's GVHD suppression after aHSCT. Importantly, Minnelide's GVHD prevention was accompanied by preservation of graft-versus-tumor activity. As Minnelide possesses anti-acute myeloid leukemia (anti-AML) activity and is being applied in clinical trials, together with the present findings, we conclude that this compound might provide a new approach for patients with AML undergoing aHSCT.

Microorganisms drive the degradation of organic matter thanks to their enzymatic versatility. However, the structure of lignocellulose poses a great challenge for the microbiota inhabiting a compost pile. Our purpose was to increase the biodegradability of vegetable waste in the early stages of the composting process by applying a microbial consortium with lignocelllulolytic capacity. For this, a previous screening was performed among the culturable microbiota from different composting processes to find inoculants with ligninocellulolytic activity. Selected strains were applied as a pure culture and as a microbial consortium. The starting material was composed of tomato plant and pruning remains mixed in a ratio (50:50 v/v), whose humidity was adjusted to around 65%. To determine the ability of both treatments to activate the biodegradation of the mixtures, moisture, organic matter, ash, C/N ratio, 4-day cumulative respirometric index (AT 4 ) and degradation rates of cellulose, hemicellulose and lignin were evaluated. Subsequently, a real composting process was developed in which the performance of the microbial consortium was compared with the composting process without inoculum (control). According to our tests, three microbial strains (Bacillus safensis, Bacillus licheniformis and Fusarium oxysporum) were selected. The results showed that the application of the bacteria strains at low doses (10 4  CFU g -1 on the complete residual material of the pile) resulted in higher rates of lignocelullose degradation after 10 days of treatment compared to that observed after application of the fungus in pure culture or untreated controls. The implementation of the strategy described in this work resulted in obtaining compost with better agronomic quality than the uninoculated controls. Therefore, the application of this consortium could be considered as an interesting tool for bioactivation of lignocellulosic waste prior to the composting process., 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Olive ( Olea europaea L.) is one of the major oil fruit tree crops worldwide. However, the mechanisms underlying olive fruit growth remain poorly understood. Here, we examine questions regarding the interaction of endoreduplication, cell division, and cell expansion with olive fruit growth in relation to the final fruit size by measuring fruit diameter, pericarp thickness, cell area, and ploidy level during fruit ontogeny in three olive cultivars with different fruit sizes. The results demonstrate that differences in the fruit size are related to the maximum growth rate between olive cultivars during early fruit growth, about 50 days post-anthesis (DPA). Differences in fruit weight between olive cultivars were found from 35 DPA, while the distinctive fruit shape became detectable from 21 DPA, even though the increase in pericarp thickness became detectable from 7 DPA in the three cultivars. During early fruit growth, intense mitotic activity appeared during the first 21 DPA in the fruit, whereas the highest cell expansion rates occurred from 28 to 42 DPA during this phase, suggesting that olive fruit cell number is determined from 28 DPA in the three cultivars. Moreover, olive fruit of the large-fruited cultivars was enlarged due to relatively higher cell division and expansion rates compared with the small-fruited cultivar. The ploidy level of olive fruit pericarp between early and late growth was different, but similar among olive cultivars, revealing that ploidy levels are not associated with cell size, in terms of different 8C levels during olive fruit growth. In the three olive cultivars, the maximum endoreduplication level (8C) occurred just before strong cell expansion during early fruit growth in fruit pericarp, whereas the cell expansion during late fruit growth occurred without preceding endoreduplication. We conclude that the basis for fruit size differences between olive cultivars is determined mainly by different cell division and expansion rates during the early fruit growth phase. These data provide new findings on the contribution of fruit ploidy and cell size to fruit size in olive and ultimately on the control of olive fruit development.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

The human microbiota plays an important role in human health and disease, through the secretion of metabolites that regulate key biological functions. We propose that microbiota metabolites represent an unexplored chemical space of small drug-like molecules in the search of new hits for drug discovery. Here, we describe the generation of a set of complex chemotypes inspired on selected microbiota metabolites, which have been synthesized using asymmetric organocatalytic reactions. Following a primary screening in CSC models, we identified the novel compound UCM-13369 ( 4b ) whose cytotoxicity was mediated by NPM1. This protein is one of the most frequent mutations of AML, and NPM1-mutated AML is recognized by the WHO as a distinct hematopoietic malignancy. UCM-13369 inhibits NPM1 expression, downregulates the pathway associated with mutant NPM1 C+, and specifically recognizes the C-end DNA-binding domain of NPM1 C+, avoiding the nucleus-cytoplasm translocation involved in the AML tumorological process. The new NPM1 inhibitor triggers apoptosis in AML cell lines and primary cells from AML patients and reduces tumor infiltration in a mouse model of AML with NPM1 C+ mutation. The disclosed phenotype-guided discovery of UCM-13369, a novel small molecule inspired on microbiota metabolites, confirms that CSC death induced by NPM1 inhibition represents a promising therapeutic opportunity for NPM1-mutated AML, a high-mortality disease., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Delirium is one of the most common adverse events in older people during hospitalization, especially in the emergency department. Reliable, easy-to-use instruments are necessary to properly manage delirium in this setting. This study aims to evaluate the diagnostic validity of the Spanish version of the 4 'A's Test (4AT) in the ED., Methods: A diagnostic accuracy study was conducted in patients over 65 years old admitted to the Emergency Department who did not have a formal diagnosis of dementia or a severe mental health disorder. Face and content validity were evaluated by an expert panel. Emergency nurses performed the evaluation with 4AT, whilst blinded and trained researchers assessed patients with the Revised Delirium Rating Scale as the gold standard. The content validity index, sensitivity, specificity, positive and negative predictive values, likelihood ratios, Youden's Index and ROC curves were calculated to evaluate the diagnostic accuracy of the instrument., Results: Of 393 eligible patients, 380 were finally analyzed. Content validity yielded a median content validity index of 4 (interquartile range: 0). The Spanish 4AT sensitivity (95.83%; 95% ECI: 78.9-99.9%), specificity (92.98%; 95% CI: 89.8-95.4%), positive predictive value (47.92%) and negative predictive value (99.7%) were satisfactory. Youden's index was 0.89. Positive likelihood ratio was 13.65, and negative likelihood ratio 0.045. The area under the curve was 0.97., Conclusions: The Spanish version of the 4AT for use in the Emergency Departments is easy-to-use and applicable. The validation results indicate that it is a valid instrument with sufficient predictive validity to identify patients at risk of delirium in the Emergency Departments. Moreover, it is a tool that facilitates the management of an adverse event that is associated with increased mortality and morbidity., (© 2024. The Author(s).)

Hereditary optic neuropathies (HONs) such as dominant optic atrophy (DOA) and Leber Hereditary Optic Neuropathy (LHON) are mitochondrial diseases characterized by a degenerative loss of retinal ganglion cells (RGCs) and are a cause of blindness worldwide. To date, there are only limited disease-modifying treatments for these disorders. The discovery of induced pluripotent stem cell (iPSC) technology has opened several promising opportunities in the field of HON research and the search for therapeutic approaches. This systematic review is focused on the two most frequent HONs (LHON and DOA) and on the recent studies related to the application of human iPSC technology in combination with biomaterials technology for their potential use in the development of RGC replacement therapies with the final aim of the improvement or even the restoration of the vision of HON patients. To this purpose, the combination of natural and synthetic biomaterials modified with peptides, neurotrophic factors, and other low- to medium-molecular weight compounds, mimicking the ocular extracellular matrices, with human iPSC or iPSC-derived cell retinal progenitors holds enormous potential to be exploited in the near future for the generation of transplantable RGC populations.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management., Competing Interests: Declaration of competing interest All authors are members of NTM Network UK, which is a network of healthcare professionals, researchers and patients from across the UK who have an interest in infections caused by non-tuberculous mycobacteria. TGDC has received non-financial support from Napp and GSK for attendance at ERS conference; TGDC's employer has received payment for his participation in advisory boards or for providing teaching sessions from AstraZeneca, Chiesi, GSK, Novartis, Boehringer Ingelheim, and Insmed, outside the submitted work. CC received non-financial support from GSK for attendance at ERS; CC's employer has received financial support from AstraZeneca through her grant application; CC received payment for her participation in advisory boards or providing teaching from AstraZeneca, Chiesi, GSK and Insmed, outside the submitted work. RH has received consultancy fees from Insmed, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM., (© 2023. The Author(s).)

Introduction: Tianeptine is a tricyclic antidepressant (TCA) without FDA-approval that acts on dopamine and norepinephrine. It has opioid agonist activity and is increasingly being used for recreational purposes to achieve an opioid-like anxiolytic effect. This can lead to clinical addiction with subsequent withdrawal symptoms resembling symptoms of opioid withdrawal. There are limited cases detailing the management of tianeptine withdrawal., Case Summary: We present the case of a 38-year-old male with chronic tianeptine use admitted to the Intensive Care Unit for treatment of encephalopathy and vital sign changes due to intake of multiple substances and suspected tianeptine withdrawal. He reported 8 to 20 g daily use of tianeptine. He was initially managed with buprenorphine/naloxone and supportive care and reported improvement in withdrawal symptoms within three days of admission. We trialed transitioning to methadone, given possible long-term benefit due to TCA-like properties, but this was discontinued due to difficulty with access on discharge. He was provided with a bridge prescription for buprenorphine/naloxone to cover until his outpatient follow-up visit and was subsequently discharged home., Conclusion: This case demonstrates management of tianeptine withdrawal in a hospitalized patient presenting with significant daily use not reported previously in the literature.

Objectives: We have previously described gestational-age-independent sonographic indices to assess fetal lung size in the right and left lungs: The Quantitative Lung Index for the right lung (QLI-R) and for the left lung (QLI-L), respectively. The purpose of this study was to evaluate the clinical cutoff point of the QLI-R to predict pulmonary hypoplasia and neonatal death., Materials and Methods: Retrospective assessment of the QLI-R in patients with left-sided congenital diaphragmatic hernia (CDH-L) and other fetal conditions at risk for fetal pulmonary hypoplasia. Cross-section and longitudinal assessment of the behavior of the QLI-R in untreated and treated patients. ROC curve analysis to determine the optimal cutoff point of the QLI-R in predicting neonatal death., Results: One hundred eighteen patients with CDH-L and other fetal conditions at risk for pulmonary hypoplasia had QLI-R measurements done. Seventeen patients were excluded for various reasons. Eleven patients with conditions other than CDH-L but at risk for pulmonary hypoplasia were used for intraclass coefficient measurements of the QLI-R. Ninety patients had CDH-L, of which 78 did not undergo antenatal intervention and in which the cutoff point for pulmonary hypoplasia and neonatal demise was assessed. Stent tracheal occlusion was performed in the remaining 12 patients with CDH-L, in which the behavior of the QLI after surgery was assessed. Analysis of the ICC showed an overall intra-rater reliability of 0.985 (Cronbach's Alpha-based). There was no correlation between gestational age and QLI-R (-0.73, Pearson correlation, p  = .72). Twenty-six of the 78 patients (33%) with CDH-L managed expectantly had a neonatal demise. A QLI-R equal to or less than 0.45 was significantly predictive of neonatal demise (area under the curve 0.64, p  = .046, sensitivity 77%). Nine of the 12 patients (75%) that underwent tracheal occlusion had neonatal survival. Of these, 10 had serial assessments of the QLI-R after surgery. An increase in the QLI-R of 0.11 was associated with a tendency for neonatal survival ( p  = .056)., Conclusion: Our study confirms that the QLI-R is a gestational-age-independent measurement of fetal lung size, with a high degree of reproducibility. In a population of expectantly managed CDH-L patients, a cutoff value of the QLI-R of 0.45 or lower is predictive of neonatal death from pulmonary hypoplasia. The QLI-R can be used to monitor fetal lung growth after tracheal occlusion, and an increase in the QLI-R is suggestive of neonatal survival. Further prospective studies are needed to confirm these findings and to explore the use of the QLI in other populations at risk for pulmonary hypoplasia and consequent neonatal demise.

Objectives: To perform an in-depth analysis of the process of transferring patients from an emergency department (ED) to other areas inside a hospital and identify possible points of failure and risk so that strategies for improvement can be developed., Material and Methods: We formed a multidisciplinary group of ED and other personnel working with hospitalized adults. The group applied failure mode and effects analysis (FMEA) to understand the in-hospital transfer processes. A risk priority scoring system was then established to assess the seriousness of each risk and the likelihood it would appear and be detected., Results: We identified 8 transfer subprocesses and 14 critical points at which failures could occur. Processes related to administering medications and identifying patients were the components that received the highest risk priority scores. Improvement strategies were established for all risks. The group created a specific protocol for in-hospital transfers and a checklist to use during handovers., Conclusion: The FMEA method helped the group to identify points when there is risk of failure during patient transfers and to define ways to improve patient safety.

Background: Acute kidney injury (AKI) is associated with high morbidity and mortality rates in the intensive care unit (ICU). In low- and middle-income countries (LMICs), epidemiological information about this condition is still scarce. Our main objective was to characterize its epidemiology, prognosis, and its treatment., Methods: This multicenter prospective cohort study included 1466 patients from 35 ICUs during 6 months in Argentina in 2018. Risk factors and outcomes in patients with and without AKI, and between AKI on admission (AKI adm ) and that developed during hospitalization (AKI hosp ) were analyzed., Results: AKI occurred in 61.3% of patients (900/1466); 72.6% were AKI adm and 27.3% AKI hosp . Risk factors were age, BMI, arterial hypertension, cardiovascular diseases, diabetes, SOFA, APACHE II, dehydration, sepsis, vasopressor use, radiocontrast, diuresis/h and mechanical ventilation. Independent predictors for AKI were sepsis, diabetes, dehydration, vasopressors on admission, APACHE II and radiocontrast use. Renal replacement therapies (RRT) requirement in AKI patients was 14.8%. Hospital mortality in AKI vs. non-AKI was 38.7% and 23.3% (p < 0.001); and in AKI adm vs. AKI hosp, 41.2% and 37.8% (p = 0.53)., Conclusions: ICU-acquired AKI has high incidence, complications and mortality. Risk factors for AKI and RRT utilization were similar to those described in other epidemiological studies. AKI adm was more frequent than AKI hosp , but had equal prognosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recent developments in deep learning have shown success in accurately predicting the location of biological markers in Optical Coherence Tomography (OCT) volumes of patients with Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). We propose a method that automatically locates biological markers to the Early Treatment Diabetic Retinopathy Study (ETDRS) rings, only requiring B-scan-level presence annotations. We trained a neural network using 22,723 OCT B-Scans of 460 eyes (433 patients) with AMD and DR, annotated with slice-level labels for Intraretinal Fluid (IRF) and Subretinal Fluid (SRF). The neural network outputs were mapped into the corresponding ETDRS rings. We incorporated the class annotations and domain knowledge into a loss function to constrain the output with biologically plausible solutions. The method was tested on a set of OCT volumes with 322 eyes (189 patients) with Diabetic Macular Edema, with slice-level SRF and IRF presence annotations for the ETDRS rings. Our method accurately predicted the presence of IRF and SRF in each ETDRS ring, outperforming previous baselines even in the most challenging scenarios. Our model was also successfully applied to en-face marker segmentation and showed consistency within C-scans, despite not incorporating volume information in the training process. We achieved a correlation coefficient of 0.946 for the prediction of the IRF area., (© 2023. The Author(s).)

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes., (Copyright © 2023 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

By means of a "live-cell" template strategy, silica replicas displaying the same morphology and topography of the mammalian cells used as templates are fabricated. The replicas are used as substrates to direct the differentiation of mesenchymal stem cells (MSCs) to predefined cell lineages. Upregulation of specific genes shows how the silica replica-based substrates have the ability to induce the molecular characteristics of the mature cell types from which they have been derived from. Thus, MSCs cultured in the presence of silica replicas of human osteoblasts (HObs) differentiate into HObs-like cells, as shown by the upregulation of specific osteogenic genes. Likewise, when MSCs are incubated with silica replicas derived from human chondrocytes, an enhanced expression of chondrogenic markers is observed. Importantly, the effects of the silica replicas are cell type-specific since the incubation of MSCs with HObs silica replicas does not result in upregulation of chondrogenic markers and vice versa. What is more, for both cases, the differentiation rate is enhanced when the silica replicas are used in combination with growth factors, suggesting a potential synergistic effect. These results demonstrate the potential of this innovative method as an efficient and cheap approach with the potential to eliminate, or at least reduce, the use of biochemically soluble compounds in stem cells research.

Study Question: Do embryologists from different European countries agree on embryo disposition decisions ('use' or 'discard') about Day 7 (>144 h post-insemination) and/or low-quality blastocysts (LQB;

The World Health Organization encourages mental health services to adopt a strategic intersectoral approach by acknowledging the potential of the arts and the value of culture on the process of mental health recovery. The aim of this study was to evaluate the impact of participatory arts in museums on mental health recovery. A quasi-experimental, pre-post and multicentre study was carried out. By using a mixed methods evaluation at baseline and at 3 months, quantitative outcome measures were used to assess the changes in recovery and social support and qualitative interviews to explore the self-perceived impact on five processes of recovery. One hundred mental health service users participated for 3 years in the face-to-face programme RecuperArte, of which the data of 54 were analysed. The results indicate a significant increase in recovery measured with the QPR-15-SP (42 vs. 44; p = 0.034) and almost significant in functional social support measured with the DUKE-UNC (41.50 vs. 43.50; p = 0.052), with almost large (r = 0.29) and medium (r = 0.26) effect sizes, respectively. Participants perceived mostly an impact on the recovery process of Meaning in life 30/54 (55.56%), Hope and optimism about the future 29/54 (53.7%) and Connectedness 21/54 (38.89%), followed by Identity 6/54 (11.11%) and Empowerment 5/54 (9.26%). The findings contribute to the growing evidence of the potential of the arts as a therapeutic tool, the value of museums as therapeutic spaces and the role of nurses in intersectoral coordination, between the mental health and cultural sectors, as facilitators and researchers of these evidence-based practices., (© 2023 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Mechanosensitive ion channels comprise a broad group of proteins that sense mechanical extracellular and intracellular changes, translating them into cation influx to adapt and respond to these physical cues. All cells in the organism are mechanosensitive, and these physical cues have proven to have an important role in regulating proliferation, cell fate and differentiation, migration and cellular stress, among other processes. Indeed, the mechanical properties of the extracellular matrix in cancer change drastically due to high cell proliferation and modification of extracellular protein secretion, suggesting an important contribution to tumor cell regulation. In this review, we describe the physiological significance of mechanosensitive ion channels, emphasizing their role in cancer and immunity, and providing compelling proof of the importance of continuing to explore their potential as new therapeutic targets in cancer research.

A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (1a-4a and 1b-2b) were prepared by the reaction between formyl (R = H) or acetyl (R = CH 3 ) nitroheterocyclic precursors [4/5-NO 2 (C 5 H 2 XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η 5 -C 5 H 5 )Fe(η 5 -C 5 H 4 SO 2 -NH-NH 2 )]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds 1a, 2b, and 3a were determined by single-crystal X-ray diffraction. The compounds showed an E-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the Trypanosoma cruzi and Trypanosoma brucei strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward T. brucei than T. cruzi. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts., (© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

McArdle disease is a rare autosomal recessive condition caused by mutations in the PYGM gene. This gene encodes the skeletal muscle isoform of glycogen phosphorylase or myophosphorylase. Patients with McArdle disease have an inability to obtain energy from their muscle glycogen stores, which manifests as a marked exercise intolerance. Nowadays, there is no cure for this disorder and recommendations are intended to prevent and mitigate symptoms. There is great heterogeneity among the pathogenic variants found in the PYGM gene, and there is no obvious correlation between genotypes and phenotypes. Here, we present the generation of the first human iPSC-based skeletal muscle model harbouring the second most frequent mutation in PYGM in the Spanish population: NM&#95;005609.4: c.2392T>C (p.Trp798Arg). To this end, iPSCs derived from a McArdle patient and a healthy control were both successfully differentiated into skeletal muscle cells using a small molecule-based protocol. The created McArdle skeletal muscle model was validated by confirming distinctive biochemical aspects of the disease such as the absence of myophosphorylase, the most typical biochemical feature of these patients. This model will be very valuable for use in future high-throughput pharmacological screenings.