Search

Xavier Busquet-Duran,1–3 Eva Maria Jiménez-Zafra,1 Josep Maria Manresa-Domínguez,2,4,5 Magda Tura-Poma,1 Olga Bosch-delaRosa,6 Anna Moragas-Roca,1 Maria Concepción Galera Padilla,1 Susana Martin Moreno,1 Emilio Martínez-Losada,1 Silvia Crespo-Ramírez,6 Ana Isabel López-Garcia,1 Pere Torán-Monserrat2,4 1Home Care Program, Support Team, PADES Granollers, Vallès Oriental Primary Health Care Services, Catalan Institute of Health, Barcelona, Spain; 2Multidisciplinary Research Group on Health and Society (GREMSAS), Barcelona, Spain; 3Department of Nursing, University Foundation of Bages (FUB), University of Vic. Central University of Catalunya, Barcelona, Spain; 4Metropolitan Nord Unit of Research Support, University Institute of Research in Primary Care (IDIAP) Jordi Gol, Barcelona, Spain; 5Department of Nursing, Autonomous University of Barcelona, Barcelona, Spain; 6Psychosocial Care Team (EAPS), Red Cross, Granollers, Barcelona, SpainCorrespondence: Xavier Busquet-Duran Email xbusquet@umanresa.catBackground: Complexity has become a core issue in caring for patients with advanced disease and/or at the end-of-life. The Hexagon of Complexity (HexCom) is a complexity assessment model in the process of validation in health-care settings. Our objective is to use the instrument to describe differences in complexity across disease groups in specific home care for advanced disease and/or at the end-of-life patients, both in general and as relates to each domain and subdomain.Methods: Cross-sectional study of home care was conducted in Catalonia. The instrument includes 6 domains of needs (clinical, psychological/emotional, social/family, spiritual, ethical, and death-related), 4 domains of resources (intrapersonal, interpersonal, transpersonal, and practical), and 3 levels of complexity (High (H), Moderate (M), and Low (L)). Interdisciplinary home care teams assessed and agreed on the level of complexity for each patient.Results: Forty-three teams participated (74.1% of those invited). A total of 832 patients were assessed, 61.4% of which were cancer patients. Moderate complexity was observed in 385 (47.0%) cases and high complexity in 347 (42.4%). The median complexity score was 51 for cancer patients and 23 for patients with dementia (p< 0.001). We observed the highest level of complexity in the social/family domain. Patients/families most frequently used interpersonal resources (80.5%).Conclusions: This study sheds light on the high-intensity work of support teams, the importance of the social/family domain and planning the place of death, substantial differences in needs and resources across disease groups, and the importance of relationship wellbeing at the end-of-life.Keywords: home care services, palliative care, terminally ill, terminal care, non-cancer patient, complexity, interdisciplinary research

Jose M García-Domínguez,1 María L Martínez-Ginés,1 Olga Carmona,2 Ana B Caminero,3 Daniel Prefasi,4 Jorge Maurino,4 Javier Ballesteros5 On behalf of the W-IMPACT Clinical Investigators 1Department of Neurology, Hospital Universitario Gregorio Marañón, Madrid, Spain; 2Department of Neurology, Hospital de Figueres, Figueres, Spain; 3Department of Neurology, Hospital Nuestra Señora de Sonsoles, Complejo Asistencial de Ávila, Ávila, Spain; 4Medical Department, Roche Farma, Madrid, Spain; 5Department of Neurosciences and CIBERSAM, Universidad del País Vasco, Leioa, Spain Background: Understanding caregiver strain may be crucial to determine which interventions are most needed to mitigate the negative impact of caring for people with multiple sclerosis (MS). The Caregiver Strain Index (CSI) is a brief self-assessment tool for measuring the caregivers’ perceived level of burden. Limited information is available on the psychometric performance of the CSI in MS.Objective: The objective of this study was to assess the factor structure and construct validity of the CSI in MS.Methods: A multicenter, cross-sectional study in adults with relapsing-remitting and primary-progressive MS (McDonald 2010 criteria) was conducted. A non-parametric item response theory (IRT) procedure, Mokken analysis, was conducted to assess the dimensional structure of the CSI. A parametric IRT model for dichotomous responses, Rasch model, was conducted to assess item characteristics. Discriminative validity was assessed comparing the distribution of its overall score between people with mild and moderate-severe disability according to the Expanded Disability Status Scale.Results: A total of 72 MS caregivers were studied. The prevalence of a high level of strain was 23.6% (n=17). Internal reliability was high (Cronbach’s alpha =0.91). According to Mokken analysis, CSI represented a unidimensional construct of caregiver burden although two of the total 13 items (#1 and #13) could not be assigned to any factor by an automatic item selection procedure. Without these items, the scalability moved from a weak (Hi =0.37) to a medium scale (Hi =0.44). However, the item characteristic curve of the Rasch model showed a range of appropriate difficulty and the item and person parameters showed good fit (Andersen likelihood ratio test =18.40, df =11; P-value =0.07; all item values for the infit). The CSI score showed a good discriminative validity between the levels of disability of the care recipient.Conclusion: The CSI questionnaire shows appropriate psychometric characteristics being a useful instrument to assess different aspects of burden in MS caregivers in clinical practice. Keywords: caregivers, multiple sclerosis, psychometrics, caregiver burden, strain

The objective of this study was to determine the effect of a constant rate infusion of medetomidine in the cortical brain activity and hemodynamic parameters in sevoflurane anesthetized puppies. Six puppies of the age of two weeks old were included in the study and were anaesthetized three times with sevoflurane. On the first anesthesia, each dog's minimum alveolar concentration (MAC) for sevoflurane was determined by the use of the tail clamp method. On the second anesthesia (sevoflurane), the puppies were anesthetized at each of five multiples of their individual's MAC, 0.75, 1, 1.25, 1.5 and 1.75 MAC, and bispectral index and cardiorespiratory parameters were registered. On the third anesthesia (sevoflurane+ medetomidine), puppies were anesthetized at each of five multiples of their individual's MAC, and medetomidine (5 µg/kg+2µg/kg/h) was administered. Mild cardiovascular depression was observed in sevoflurane+medetomidine in comparison with sevoflurane. Cortical and antinociceptive effects were not observed with medetomidine infusion although a mature EEG response to noxious stimulation would not have developed in puppies. Central alpha-2 adrenoreceptors would be immature in puppies during the first two weeks of life, and for this reason, medetomidine would not produce sedative and analgesic effects in young puppies. More studies have to be performed to support this statement. [ABSTRACT FROM AUTHOR]

In Spain, immigration is a recent and exponentially increasing phenomenon. In the geographical area corresponding to the department of health no.18, most immigrants come from South America, Morocco and Rumania. The feeding pat-terns of these people have a strategic value regarding culture and health. We present a work in which 170 immigrants have been interviewed, with the aim of assessing one of the main aspects: food consumption. The results indicate that immigrants maintain a balanced consumption of immediate principles, although some basic foods groups are insufficiently consumed by them. In addition, the length of their stay could be considered a crucial factor towards the assimilation of the currently unbalanced nutritional pattern of Spanish people. [ABSTRACT FROM AUTHOR]

Background: Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment., Objectives: This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction., Methods: In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity)., Results: A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity., Conclusion: This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS., Competing Interests: Declarations Funding Writing and editorial assistance was provided by Content Ed Net (Madrid, Spain) with funding from Biogen. Conflict of interest C.A. has received lecture honoraria, consultancy fees, and travel expenses from Biogen, Bristol Mayers Squibb, Merck, Novartis, Sanofi-Genzyme and Roche. A.A.T. has received fees as a speaker, consultant or travel support from Biogen, Almirall, Merck, Roche, Sanofi, Sandoz and Janssen. E.A. has no disclosures for financial affiliation, financial support nor grants moneys and has disclosure for speaker honorarium from Novartis, Merck and Biogen. JM.G.D. has received compensation as a consultant, researcher, or speaker from Biogen, Sanofi, Roche, Zenas Biopharma, Almirall, Novartis, Merck, Bristol-Myers-Squidd, and Johnson & Johnson. PM-E has received speaker and consultation fees from Allergan, Almirall, Biogen Idec, Merck, Merz, Novartis and Sanofi-Genzyme. V.G.Q has no conflict of interest related to this work. L.C.F. has received lecture honoraria, consultancy fees, clinical research funding, and travel expenses from Almirall, Amgen, AstraZeneca, Biogen, Bristol Mayers Squibb, Janssen, Merck, Neuraxpharma, Novartis, Sanofi-Genzyme, Roche. C.O.G. has received speaker and consultation fees from Alexion, Biogen Idec, BMS, Horizon, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. V.R.G. has received fees as a speaker, consultant or travel support from Almirall, Merck, Alexion, Roche and Sanofi. AB.C.R. has received honoraria as speaker/meeting moderator/courses/symposium organized by Almirall Prodesfarma S.A, Biogen Idec Inc, Bristol-Myers-Squibb, Janssen Pharmaceutical; Merck-Serono, Mylan, Novartis Pharmaceutical, Roche, Sanofi-Genzyme, Teva Pharmaceuticals; and for congress assistance from Biogen Idec Inc, Bial, Merck-Serono, Novartis Pharmaceutical, Roche, Sanofi-Genzyme, Teva Pharmaceuticals. J.R. has received speaking/consulting fees and/or travel funding from Merck, Sanofi-Genzyme, Roche, Biogen, Novartis, BMS, Jannsen and Teva. O.S. has received fees from Almirall, Biogen, Novartis, Merck, Sanofi, Alter, Bial, Teva, Neuraxfarma, Esteve, Pfizer, Roche and UCB. L.F. has no conflict of interest related to this work. F.P.P has no conflict of interest related to this work. A.A.R. has received fees as a speaker and advisor, and funding for attendance at congresses and other medical meetings, from Bayer, Biogen, Bristol, Janssen, Merck, Novartis, Roche, Sanofi and Teva. J.A.L. received consultant fees from Merck. F.I. has received speaker honoraria and travel reimbursement from Biogen, Merck, Novartis, Roche Spain, and Genzyme-Sanofi. V.C.R has no conflict of interest related to this work. AJ.C.V. has no conflict of interest related to this work. L.B. has no conflict of interest related to this work. V.G. has received speaker fees from Merck, Roche, Biogen, Novartis and Sanofi. L.A.R.A. declares to have received travel aid and financial compensation for talks from BMS and Novartis. R.G.R received payments from Biogen for participating in training conferences. AT.C.O. has received payments from Biogen for participating in training conferences for other professionals. JL.S.M. accepted travel compensation from Novartis, Merck and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in clinical trials by Biogen, Sanofi, Merck and Roche. D.P.R. has received honoraria as a speaker, funding to attend courses and conferences, and consultancies and research grants from Merck, Biogen, Novartis, Sanofi, Teva, Roche and Almirall. F.G.M has received speaker honoraria and travel reimbursement from Biogen, Merck, Novartis, Roche Spain, and Genzyme-Sanofi. L.H.E. has received speaker and consultation fees from Biogen, Merck, Novartis, Roche and Sanofi. Ethics approval The research protocol received approval from the independent ethics committee at the Hospital Universitario de La Princesa (10 November 2022, acta CEIM 5723). Consent to participate This investigation adhered to the principles of the Helsinki Declaration and complied with the EU General Data Protection Regulation (GDPR). All personal identifiers were excluded from the findings. Consent for publication Not applicable. Data availability statement Data are available from the corresponding author upon reasonable request. Author contributions CAH and VML made substantial contributions to the conception and design of the work, interpretation of data and drafting the manuscript. All authors contributed to the acquisition of data and revised the manuscript and approved the version to be published. Code availability Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile., Methods: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment., Results: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response., Conclusion: In a developing country, TL is an adequate option for appropriately selected DTC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The functional properties of edible insects can be explored by a joint use of novel technologies. This work applied varied pre-treatments (ultra-sound-assisted extraction, UAE; microwave-assisted extraction, MAE; temperature-assisted extraction, TAE; CO2-assisted extraction) and solvents (water, ethanol, water:ethanol) in Tenebrio molitor beetles to enhance the extraction of phenolic compounds with antioxidant activity. An enzymatic hydrolysis (EH) was performed in wet and treated biomasses to determine the protein hydrolysis. Higher phenolic compounds and antioxidant activity was released after MAE using water as solvent compared to the other treatments and solvents. Treatments decreased 32 %, 19 % and 30 % the protein, chitin and lipids content. EH improved protein and amino acids hydrolysis in the MAE-treated insects, followed by UAE and TAE treatments. In conclusion, MAE was the most effective to release phenolics and antioxidant activity from T. molitor beetles, while using MAE followed by EH improved protein and amino acids hydrolysis, envisioning valuable applications for this insect biomass., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications., Methods: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021., Results: Screening rates increased for all tests across different time periods (2000-2007, 2008-2016, and 2017-2021) and was the most influential factor for NPM1, FLT3-ITD, and next-generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3-ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000-2007 and only reached 3.5% in 2008-2016, but significantly increased to 72% in 2017-2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702-7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901-2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy., Conclusions: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real-world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades., (© 2024 American Cancer Society.)

Background: The assessment of serum neurofilament light chain (sNfL) concentration in multiple sclerosis (MS) is a useful tool for predicting clinical outcomes and assessing treatment response. However, its use in clinical practice is still limited. We aimed to assess how measurement of sNfL influences neurologists' treatment decisions in MS., Methods: We conducted a cross-sectional, web-based study in collaboration with the Spanish Society of Neurology. Neurologists involved in MS care were presented with different simulated case scenarios of patients experiencing either their first demyelinating MS event or a relapsing-remitting MS. The primary outcome was therapeutic inertia (TI), defined as the absence of treatment initiation or intensification despite elevated sNfL levels. Nine cases were included to estimate the TI score (range 0-9, where higher values represented a higher degree of TI)., Results: A total of 116 participants were studied. Mean age (standard deviation-SD) was 41.9 (10.1) years, 53.4 % male. Seventy-eight (67.2 %) were neurologists fully dedicated to the care of demyelinating disorders. Mean (SD) TI score was 3.65 (1.01). Overall, 92.2 % of participants (n = 107) presented TI in at least 2/9 case scenarios. The lack of full dedication to MS care (p = 0.014), preference for taking risks (p = 0.008), and low willingness to adopt evidence-based innovations (p = 0.009) were associated with higher TI scores in the multivariate analysis after adjustment for confounders., Conclusion: TI was a common phenomenon among neurologists managing MS patients when faced with the decision to initiate or escalate treatment based on elevated sNfL levels. Identifying factors associated with this phenomenon may help optimize treatment decisions in MS care., Competing Interests: Declaration of competing interest Gustavo Saposnik received consulting fees from Roche Farma Spain and is supported by the University of Toronto Scientific Merit award. He also receives a modest stipend from the World Stroke Organization as the Editor in Chief of the World Stroke Academy. Enric Monreal reported receiving research grants, travel support, or honoraria for speaking engagements from Almirall, Merck, Roche, Sanofi, Bristol Myers Squibbb, Biogen, Janssen, and Novartis. Jose M García-Domínguez received honoraria as speaker, advisor and researcher from Almirall, Bristol Myers Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. Jose E Meca-Lallana received honoraria as a consultant, chairman and lecturer in meetings and participated in clinical trials and other research projects promoted by Alexion, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Lamberto Landete received honoraria for participating in advisory boards and scientific and educational activities from Almirall, Bayer, Biogen, Bristol Myers Squibb, Sanofi, Merck, Novartis, UCB, Roche, and Teva. Virginia Meca-Lallana received consulting and speaking fees from Almirall, Biogen, Genzyme, Janssen, Merck, Novartis, Roche, Terumo, Sanofi, Teva, and Bristol Myers Squibb. Luis Querol received speaker honoraria from Merck, Sanofi, Roche, Biogen, Grifols and CSL Behring; provided expert testimony for Grifols, Johnson & Johnson, Annexon Pharmaceuticals, Sanofi, Novartis, Takeda, and CSL-Behring; and received research funds from Roche, UCB, and Grifols. Eduardo Agüera received speaking honoraria from Roche, Novartis, Merck, Sanofi, and Biogen. Sergio Martínez-Yélamos received honoraria for participating on advisory boards and for collaborations as consultant and scientific communications; they also received research support as well as funding for travel and congress expenses from Roche, Biogen Idec, Novartis, TEVA, Merck, Genzyme, Sanofi, Bayer, Almirall, and Bristol Myers Squibb. Luisa M Villar reported receiving research grants and personal fees from Merck, Roche, Sanofi, Bristol Myers Squibb, Biogen, and Novartis. Ana B Caminero received courses and honoraria for her participation as speaker/meeting moderator/symposia organizer from Alter, Almirall, Bayer, Bial, Biogen, Bristol Myers Squibb, Lilly, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva, and UCB; and support to attend scientific meetings from Biogen, Bial, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Rocío Gómez-Ballesteros, Elisa Salas, Nicolas Medrano, Elena García-Arcelay, and Jorge Maurino are employees of Roche Farma Spain., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Excessive noise in intensive care units poses a significant challenge, impacting both patients and staff by elevating stress, disrupting recovery, and impeding effective communication among healthcare professionals. Despite the World Health Organization recommending noise levels below 35 dB, alarms in these units often surpass these limits, contributing to consistently high noise levels., Objectives: The aim of this study is to explore intensive care unit patients' experiences with music therapy sessions during invasive procedures., Methods: This study was conducted using a qualitative hermeneutic phenomenological methodology grounded in Heideggerian philosophy. Interventions were conducted with a music therapist, and 14 in-depth interviews were collected. Reflexive inductive thematic analysis was performed., Results/findings: From the thematic analysis extracted from the 14 personal interviews, three themes were described that represent the bulk of the experiences and emotions of the study participants following the completion of the music therapy sessions. The most noteworthy results are described in the following, organised according to each theme: (i) music therapy against noise, sounds, and light; (ii) music therapy in the face of invasive tests and techniques; and (iii) music therapy as a strategy and tool., Conclusions: Music therapy has significant potential to enhance the quality of life for patients in the intensive care unit. Music therapy can promote relaxation, reduce stress and anxiety, alleviate pain and discomfort, and improve emotional and physical wellbeing during patients' stay and invasive procedures., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen., Methods: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed., Results: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases., Conclusions: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended., Competing Interests: Declarations Conflict of interest None. Ethical statement No ethical conflicts have arisen during the course of this research. The authors declare that they have no competing interests, financial or otherwise, that could have influenced the outcomes of this study. Informed consent statement All four patients provided their informed consent for the disclosure of their cases for scientific and educational purposes., (© 2024. Fondazione Società Italiana di Neurologia.)

Mutations in the lipoyltransferase 1 ( LIPT1 ) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

Objectives: The aim of this study was to describe grandmothers' experiences of taking care of their grandchildren in terms of their care-giving tasks, motivations and emotions., Methods: A qualitative phenomenological study was conducted. Purposive sampling was used, based on the relevance of the research question. Seventeen participants were included, women ≥ 65 years old, grandmothers who care for their grandchildren at least 10 h per week and who attended the Nursing units of the Primary Care Health Centers (Madrid Public Health Service). Seventeen in-depth interviews were conducted. The interviews were audio-recorded, transcribed verbatim and thematic analysis was carried out from the perspective of hermeneutic phenomenology. For the analysis, the Excel program was used to organize and share the coding process. Also, we followed COREQ guidelines., Results: Four main themes were identified: (a) Care out of obligation, where participants feel an obligation to help their children by caring for grandchildren, regardless of their number, and prefer to do so voluntarily; (b) Care out of responsibility, where grandmothers see their role as a responsibility that includes saving costs by caring for grandchildren and facilitating their children's work life balance; (c) Care as a social duty, reflecting a moral commitment inherited from their mothers to help future generations; and (d) Construction of care from a gender perspective, where grandmothers, as women, primarily assume the care and upbringing of grandchildren., Discussion: Our results contribute to increase knowledge about childcare provided by grandmothers to their grandchildren. Grandmothers become fundamental pillars of families by helping their children balance family and work. Behind this care there is a strong sense of obligation, duty and generational responsibility. Grandmothers' help presents differences in the distribution of tasks and care by sex. Identifying factors that motivate grandmothers to care for their grandchildren helps nurses to perform higher quality comprehensive care., (© 2024. The Author(s).)

Nanocellulose, a nanoscale derivative from renewable biomass sources, possesses remarkable colloidal properties in water, mechanical strength, and biocompatibility. It emerges as a promising bio-based dispersing agent for various nanomaterials in water. This mini-review explores the interaction between cellulose nanomaterials (nanocrystals or nanofibers) and water, elucidating how this may enable their potential as an eco-friendly dispersing agent. We explore the potential of nanocellulose derived from top-down processes, nanocrystals, and nanofibers for dispersing carbon nanomaterials, semiconducting oxide nanoparticles, and other nanomaterials in water. We also highlight its advantages over traditional methods by not only effectively dispersing those nanomaterials but also potentially eliminating the need for further chemical treatments or supporting stabilizers. This not only preserves the exceptional properties of nanomaterials in aqueous dispersion, but may even lead to the emergence of novel hybrid functionalities. Overall, this mini-review underscores the remarkable versatility of nanocellulose as a green dispersing agent for a variety of nanomaterials, inspiring further research to expand its potential to other nanomaterials and applications.

Context: Music listening (ML) has been shown to have a beneficial effect on patients with cancer. However, novel intervention approaches are needed., Objectives: We aimed to determine whether ML based on the iso-principle, conducted using a mobile application (GloMus), improves symptom burden, quality of life (QoL), anxiety, and depression in patients undergoing stem cell transplantation (SCT) and intensive induction chemotherapy for acute myeloid leukemia (AML)., Methods: In this randomized controlled clinical trial, we assigned 71 patients to the ML or standard care (SC) groups, stratified by the reason for admission (AML, allogeneic-SCT, or inpatient/outpatient autologous-SCT). Upon admission, participants in the ML groups were invited to undergo daily ML sessions designed to change negative moods into positive ones (iso-principle). The intervention consisted of listening to pre-recorded classical music ordered by beats per minute and tonality. Symptom burden (Edmonton Symptom Assessment System-Revised) was assessed in the ML groups before and after each session. Anxiety, depression (Hospital Anxiety and Depression Scale), and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation/Leukemia) were measured weekly in the ML and SC groups., Results: Symptom burden in both allogeneic- and inpatient autologous-SCT ML groups reduced after the intervention. In all experimental groups, clinically important improvements were observed after ML sessions. No differences were found between the groups (ML vs. SC) at different weeks of admission regarding anxiety, depression, and QoL., Conclusions: ML based on our innovative iso-principle strategy, conducted using GloMus, reduced the symptom burden in patients undergoing allogeneic- and inpatient autologous-SCT (ClinicalTrials.gov number, NCT05696457)., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations.

Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease., Materials and Methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter., Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LNgrowth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up., Conclusion: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Background: Hypoparathyroidism is characterized by chronic hypocalcemia with low or abnormal parathyroid hormone levels. Thyroid surgery remains a predominant cause of hypoparathyroidism, often preventable by partial thyroidectomy. Although hypoparathyroidism can impair quality of life (QOL), data remain limited for Latin America. We aimed to characterize clinical manifestations and QOL in patients with postsurgical hypoparathyroidism., Methods: This case-control study included patients (&gt;18 years) who underwent total thyroidectomy (TT) for differentiated thyroid cancer (DTC) with postsurgical hypoparathyroidism (Group 1, Cases) and those with DTC who underwent TT without postsurgical hypoparathyroidism (Group 2, Controls). Clinical records were collected, and the SF-36v2 QOL survey and a structured symptom survey were applied. A logistic multivariate regression analysis was performed., Results: This study included 106 subjects (Group 1, N=41; Group 2, N=65). Group 1 patients were younger, had a higher frequency of lymph node resection, and more frequently received Ι-131 than Group 2 patients (p&lt;0.05). In the SF-36v2 survey, Group 1 had fewer physical-functioning scores (odds ratio, 3.8; 95% confidence interval, 1.2-11.7) and lower scores in mental and physical components than Group 2 and national records. Commonly reported symptoms include paresthesia, daily fatigue, and memory alterations. Treatment adherence rates were 56% and 71% for calcium and calcitriol, respectively. Furthermore, 24% of patients experienced one or more hypoparathyroidism drug-related adverse effects., Conclusions: Patients with postsurgical hypoparathyroidism had an impaired QOL, a high frequency of disease-associated symptoms, and limited treatment adherence. These results should be considered when deciding the best surgical alternative for DTC.

The brewery industry is under economic and environmental pressure to minimize residual management costs, particularly brewery spent grain (BSG), which accounts for 80-85% (w/w) of the total by-products generated. BSG is a lignocellulosic material primarily composed of carbohydrates, proteins and lipids. Developing a biorefinery model for conversion of BSG into value-added products is a plausible idea. Previous work optimized the pretreatment of BSG with the ionic liquid [N 1112OH ][Gly] and further release of fermentable sugar-containing solutions by enzymatic hydrolysis, using an enzymatic cocktail obtained by solid-state fermentation of BSG with Aspergillus brasiliensis CECT 2700 and Trichoderma reesei CECT 2414. The current work ends the biorefinery process, studying the fermentation of these culture media with two LAB strains, Lactobacillus pentosus CECT 4023 and Lactobacillus plantarum CECT 221, from which the production of organic acids, bacteriocins, and microbial biosurfactants (mBS) was obtained. In addition to the bacteriocin activity observed, a mass balance of the whole biorefinery process quantified the production of 106.4 g lactic acid and 6.76 g mBS with L. plantarum and 116.1 g lactic acid and 4.65 g mBS with L. pentosus from 1 kg of dry BSG. Thus, BSG shows a great potential for waste valorization, playing a major role in the implementation of biomass biorefineries in circular bioeconomy., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ-67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first-in-human, open-label, phase I, dose-escalation/dose-expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ-67571244 was administered intravenously or subcutaneously using step-up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose-escalation cohorts (n = 68) and before starting dose-expansion. Overall, 11 (16.2%) patients experienced ≥1 dose-limiting toxicity; all experienced ≥1 treatment-emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ-67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion-related reactions, and elevated liver function tests. A prolonged step-up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T-cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ-67571244 efficacy was not achieved, thus MTD and RP2D were not determined., (© 2024 Janssen Research and Development, LLC. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)