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1.
Proc Natl Acad Sci U S A ; 120(33): e2300839120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549271

RESUMO

Mammalian hair cells do not functionally regenerate in adulthood but can regenerate at embryonic and neonatal stages in mice by direct transdifferentiation of neighboring supporting cells into new hair cells. Previous work showed loss of transdifferentiation potential of supporting cells is in part due to H3K4me1 enhancer decommissioning of the hair cell gene regulatory network during the first postnatal week. However, inhibiting this decommissioning only partially preserves transdifferentiation potential. Therefore, we explored other repressive epigenetic modifications that may be responsible for this loss of plasticity. We find supporting cells progressively accumulate DNA methylation at promoters of developmentally regulated hair cell genes. Specifically, DNA methylation overlaps with binding sites of Atoh1, a key transcription factor for hair cell fate. We further show that DNA hypermethylation replaces H3K27me3-mediated repression of hair cell genes in mature supporting cells, and is accompanied by progressive loss of chromatin accessibility, suggestive of facultative heterochromatin formation. Another subset of hair cell loci is hypermethylated in supporting cells, but not in hair cells. Ten-eleven translocation (TET) enzyme-mediated demethylation of these hypermethylated sites is necessary for neonatal supporting cells to transdifferentiate into hair cells. We also observe changes in chromatin accessibility of supporting cell subtypes at the single-cell level with increasing age: Gene programs promoting sensory epithelium development loses chromatin accessibility, in favor of gene programs that promote physiological maturation and function of the cochlea. We also find chromatin accessibility is partially recovered in a chronically deafened mouse model, which holds promise for future translational efforts in hearing restoration.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Metilação de DNA , Animais , Camundongos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cóclea/metabolismo , Regeneração/genética , Cromatina/metabolismo , Mamíferos/genética
2.
Proc Natl Acad Sci U S A ; 120(34): e2301301120, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37585469

RESUMO

The auditory organ of Corti is comprised of only two major cell types-the mechanosensory hair cells and their associated supporting cells-both specified from a single pool of prosensory progenitors in the cochlear duct. Here, we show that competence to respond to Atoh1, a transcriptional master regulator necessary and sufficient for induction of mechanosensory hair cells, is established in the prosensory progenitors between E12.0 and 13.5. The transition to the competent state is rapid and is associated with extensive remodeling of the epigenetic landscape controlled by the SoxC group of transcription factors. Conditional loss of Sox4 and Sox11-the two homologous family members transiently expressed in the inner ear at the time of competence establishment-blocks the ability of prosensory progenitors to differentiate as hair cells. Mechanistically, we show that Sox4 binds to and establishes accessibility of early sensory lineage-specific regulatory elements, including ones associated with Atoh1 and its direct downstream targets. Consistent with these observations, overexpression of Sox4 or Sox11 prior to developmental establishment of competence precociously induces hair cell differentiation in the cochlear progenitors. Further, reintroducing Sox4 or Sox11 expression restores the ability of postnatal supporting cells to differentiate as hair cells in vitro and in vivo. Our findings demonstrate the pivotal role of SoxC family members as agents of epigenetic and transcriptional changes necessary for establishing competence for sensory receptor differentiation in the inner ear.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Fatores de Transcrição SOXC , Animais , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cóclea/metabolismo , Células Ciliadas Auditivas/metabolismo , Diferenciação Celular , Fatores de Transcrição/metabolismo , Epigênese Genética , Órgão Espiral , Regulação da Expressão Gênica no Desenvolvimento , Mamíferos/metabolismo
3.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34266958

RESUMO

During embryonic development, hierarchical cascades of transcription factors interact with lineage-specific chromatin structures to control the sequential steps in the differentiation of specialized cell types. While examples of transcription factor cascades have been well documented, the mechanisms underlying developmental changes in accessibility of cell type-specific enhancers remain poorly understood. Here, we show that the transcriptional "master regulator" ATOH1-which is necessary for the differentiation of two distinct mechanoreceptor cell types, hair cells in the inner ear and Merkel cells of the epidermis-is unable to access much of its target enhancer network in the progenitor populations of either cell type when it first appears, imposing a block to further differentiation. This block is overcome by a feed-forward mechanism in which ATOH1 first stimulates expression of POU4F3, which subsequently acts as a pioneer factor to provide access to closed ATOH1 enhancers, allowing hair cell and Merkel cell differentiation to proceed. Our analysis also indicates the presence of both shared and divergent ATOH1/POU4F3-dependent enhancer networks in hair cells and Merkel cells. These cells share a deep developmental lineage relationship, deriving from their common epidermal origin, and suggesting that this feed-forward mechanism preceded the evolutionary divergence of these very different mechanoreceptive cell types.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Ciliadas Auditivas/metabolismo , Proteínas de Homeodomínio/metabolismo , Mecanorreceptores/metabolismo , Fator de Transcrição Brn-3C/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular , Cóclea/metabolismo , Elementos Facilitadores Genéticos , Epigênese Genética , Células Ciliadas Auditivas/citologia , Proteínas de Homeodomínio/genética , Humanos , Células de Merkel/metabolismo , Camundongos , Fator de Transcrição Brn-3C/genética
4.
Proc Natl Acad Sci U S A ; 117(24): 13552-13561, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32482884

RESUMO

Precise control of organ growth and patterning is executed through a balanced regulation of progenitor self-renewal and differentiation. In the auditory sensory epithelium-the organ of Corti-progenitor cells exit the cell cycle in a coordinated wave between E12.5 and E14.5 before the initiation of sensory receptor cell differentiation, making it a unique system for studying the molecular mechanisms controlling the switch between proliferation and differentiation. Here we identify the Yap/Tead complex as a key regulator of the self-renewal gene network in organ of Corti progenitor cells. We show that Tead transcription factors bind directly to the putative regulatory elements of many stemness- and cell cycle-related genes. We also show that the Tead coactivator protein, Yap, is degraded specifically in the Sox2-positive domain of the cochlear duct, resulting in down-regulation of Tead gene targets. Further, conditional loss of the Yap gene in the inner ear results in the formation of significantly smaller auditory and vestibular sensory epithelia, while conditional overexpression of a constitutively active version of Yap, Yap5SA, is sufficient to prevent cell cycle exit and to prolong sensory tissue growth. We also show that viral gene delivery of Yap5SA in the postnatal inner ear sensory epithelia in vivo drives cell cycle reentry after hair cell loss. Taken together, these data highlight the key role of the Yap/Tead transcription factor complex in maintaining inner ear progenitors during development, and suggest new strategies to induce sensory cell regeneration.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Autorrenovação Celular , Órgão Espiral/embriologia , Órgão Espiral/metabolismo , Células-Tronco/citologia , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Ciclo Celular , Proteínas de Ciclo Celular/genética , Diferenciação Celular , Regulação da Expressão Gênica no Desenvolvimento , Células Ciliadas Auditivas , Camundongos , Órgão Espiral/citologia , Ligação Proteica , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
5.
Acta Neuropsychiatr ; : 1-9, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34903309

RESUMO

A total of 80% of fibromyalgia (FM) population have reported poor sleep. In this regard, the pineal gland, involved in circadian rhythm processes as a key neuroendocrine organ which mainly synthesises and secretes melatonin, has never been studied before in this population. Therefore, this study aimed to evaluate the parenchyma pineal volume and its relation to sleep hours, sleep quality index and melatonin level at night. A total of 50 participants, 30 women with FM and 20 healthy control women underwent cranial magnetic resonance imaging. The total pineal volume, cyst pineal volume and parenchyma pineal volume were manually calculated in cubic millimetres. Also, the total pineal volume was estimated using Hasehawa method. Parenchyma pineal volume was significantly correlated with sleep hours (p-value = 0.041) and nocturnal melatonin level (p-value = 0.027). Moreover, there was also a non-significant correlation between parenchyma pineal volume and sleep quality index (p-value = 0.055). Furthermore, a mean parenchyma pineal volume of 102.00 (41.46) mm³ was observed, with a prevalence of 29.60% cyst in FM group. This is the first study that has reported pineal gland volumes, cyst prevalence and correlative relationships between parenchyma pineal volume and sleep hours and melatonin levels in women with FM.

6.
J Environ Sci (China) ; 100: 62-73, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33279054

RESUMO

We report the preparation of poly(3,4-ethylene dioxythiophene) (PEDOT)-modified polyvinylidene fluoride electrospun fibers and their use as a novel adsorbent material for the removal of the anionic dye Methyl Orange (MO) from aqueous media. This novel adsorbent material can be used to selectively remove MO on a wide pH range (3.0-10.0), with a maximum capacity of 143.8 mg/g at pH 3.0. When used in a recirculating filtration system, the maximum absorption capacity was reached in a shorter time (20 min) than that observed for batch mode experiments (360 min). Based on the analyses of the kinetics and adsorption isotherm data, one can conclude that the predominant mechanism of interaction between the membrane and the dissolved dye molecules is electrostatic. Besides, considering the estimated values for the Gibbs energy, and entropy and enthalpy changes, it was established that the adsorption process is spontaneous and occurs in an endothermic manner. The good mechanical and environmental stability of these membranes allowed their use in at least 20 consecutive adsorption/desorption cycles, without significant loss of their characteristics. We suggest that the physical-chemical characteristics of PEDOT make these hybrid mats a promising adsorbent material for use in water remediation protocols and effluent treatment systems.


Assuntos
Poluentes Químicos da Água , Adsorção , Compostos Azo , Compostos Bicíclicos Heterocíclicos com Pontes , Concentração de Íons de Hidrogênio , Cinética , Polímeros , Polivinil , Termodinâmica
7.
Ecotoxicol Environ Saf ; 201: 110833, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535368

RESUMO

The largest mercury (Hg) mining district in the world is located in Almadén (Spain), with well-known environmental impacts in the surrounding ecosystem. However, the impact of mercury on the health of the inhabitants of this area has not been documented accordingly. This study aims to carry out a probabilistic human health risk assessment using Bayesian modeling to estimate the non-carcinogenic risk related to Hg through multiple exposure pathways. Samples of vegetables, wild mushrooms, fish, soil, water, and air were analyzed, and adult residents were randomly surveyed to adjust the risk models to the specific population data. On the one hand, the results for the non-carcinogenic risk based on Hazard Quotient (HQ) showed unacceptable risk levels through ingestion of Hg-contaminated vegetables and fish, with HQ values 20 and 3 times higher, respectively, than the safe exposure threshold of 1 for the 97.5th percentile. On the other hand, ingestion of mushrooms, dermal contact with soil, ingestion of water, dermal contact with water and inhalation of air, were below the safety limit for the 97.5th percentile, and did not represent a risk to the health of residents. In addition, the probabilistic approach was compared with the conservative deterministic approach, and similar results were obtained. This is the first study conducted in Almadén, which clearly reveals the high levels of human health risk to which the population is exposed due to the legacy of two millennia of Hg mining.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/análise , Mercúrio/análise , Mineração , Adulto , Agaricales/química , Ar/análise , Animais , Teorema de Bayes , Ecossistema , Peixes/metabolismo , Humanos , Distribuição Aleatória , Medição de Risco , Solo/química , Espanha , Verduras/química
8.
Anal Biochem ; 575: 27-35, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30917944

RESUMO

We describe the use of a hybrid magnetic nanocomposite (HMNC) for the extraction and purification of plasmid DNA (pDNA) from Escherichia coli aqueous solutions. The HMNC, which was synthesized via emulsion polymerization, was characterized by transmission electron microscopy, scanning electron microscopy, UV-Vis spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering and magnetic measurements. The results confirmed the incorporation of polyaniline (Pani) in its conducting form onto a core formed by the magnetic iron oxide, with the hybrid particles presenting an average size of (95 ±â€¯30) nm and a saturation magnetization of 30 emu/g. The yield, purity and quality of the pDNA purified by using the Pani HMNC were evaluated by UV-Vis spectroscopy, agarose gel electrophoresis, and Polymerase Chain Reaction (PCR), respectively. An average yield of ~6.9 µg was obtained in the DNA extraction process, with the collected material presenting a good purity (a ₳260/280 ratio in the 1.68-1.82 range) and an excellent quality, as confirmed by subsequent PCR assays. Hence, this HMNC appears as a promising material for use in pDNA purification protocols, and we suggest that this novel HMNC-based methodology can be of general interest and find widespread application in different biomedical procedures.


Assuntos
Compostos de Anilina/química , DNA/química , Compostos Férricos/química , Magnetismo , Nanocompostos/química , Plasmídeos , Silício/química
9.
J Neurosci ; 36(17): 4758-70, 2016 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27122034

RESUMO

UNLABELLED: Cisplatin is a common and effective chemotherapeutic agent, yet it often causes permanent hearing loss as a result of sensory hair cell death. The causes of sensitivity to DNA-damaging agents in nondividing cell populations, such as cochlear hair and supporting cells, are poorly understood, as are the specific DNA repair pathways that protect these cells. Nucleotide excision repair (NER) is a conserved and versatile DNA repair pathway for many DNA-distorting lesions, including cisplatin-DNA adducts. Progressive sensorineural hearing loss is observed in a subset of NER-associated DNA repair disorders including Cockayne syndrome and some forms of xeroderma pigmentosum. We investigated whether either of the two overlapping branches that encompass NER, transcription-coupled repair or global genome repair, which are implicated in Cockayne syndrome and xeroderma pigmentosum group C, respectively, modulates cisplatin-induced hearing loss and cell death in the organ of Corti, the auditory sensory epithelium of mammals. We report that cochlear hair cells and supporting cells in transcription-coupled repair-deficient Cockayne syndrome group A (Csa(-/-)) and group B (Csb(-/-)) mice are hypersensitive to cisplatin, in contrast to global genome repair-deficient Xpc(-/-) mice, both in vitro and in vivo We show that sensory hair cells in Csa(-/-) and Csb(-/-) mice fail to remove cisplatin-DNA adducts efficiently in vitro; and unlike Xpc(-/-) mice, Csa(-/-) and Csb(-/-) mice lose hearing and manifest outer hair cell degeneration after systemic cisplatin treatment. Our results demonstrate that Csa and Csb deficiencies predispose to cisplatin-induced hearing loss and hair/supporting cell damage in the mammalian organ of Corti, and emphasize the importance of transcription-coupled DNA repair in the protection against cisplatin ototoxicity. SIGNIFICANCE STATEMENT: The utility of cisplatin in chemotherapy remains limited due to serious side effects, including sensorineural hearing loss. We show that mouse models of Cockayne syndrome, a progeroid disorder resulting from a defect in the transcription-coupled DNA repair (TCR) branch of nucleotide excision repair, are hypersensitive to cisplatin-induced hearing loss and sensory hair cell death in the organ of Corti, the mammalian auditory sensory epithelium. Our work indicates that Csa and Csb, two genes involved in TCR, are preferentially required to protect against cisplatin ototoxicity, relative to global genome repair-specific elements of nucleotide excision repair, and suggests that TCR is a major force maintaining DNA integrity in the cochlea. The Cockayne syndrome mice thus represent a model for testing the contribution of DNA repair mechanisms to cisplatin ototoxicity.


Assuntos
Cisplatino/toxicidade , Síndrome de Cockayne/genética , Reparo do DNA/genética , Perda Auditiva/induzido quimicamente , Mutação/genética , Animais , Morte Celular , Cóclea/metabolismo , Adutos de DNA , Enzimas Reparadoras do DNA/genética , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Xeroderma Pigmentoso/genética
10.
Sci Med Footb ; 8(2): 179-186, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-36695090

RESUMO

This study novelty aimed to investigate the influence of manipulating the available time to perform the training tasks on soccer players´ ocular metrics, following training. Specifically, pupillary response (pupil diameter) and saccadic features (latency, accuracy, velocity, and number) were measured with a portable eye tracker following training to reflect the mental load accumulated by players during the training sessions. Nine semi-elite soccer players performed two training sessions, based on large-sided games, on an artificial grass field. These two sessions were composed of the same tasks but varying the required time to complete the task goals (Session 1: No time limitations to perform the tasks; Session 2: Limited time to perform the tasks). The participants performed, before (pre-test) and after (post-test) each training session, a prosaccade task in a room near the playing field. Findings revealed a differentiated effect of the available time to complete the training tasks on ocular metrics because significant differences were found in all variables after training (p < .001 for pupil diameter; p < .01 for saccade accuracy and number of saccades; p < .05 for saccade velocity and latency). Ocular metrics could be a promising tool to evaluate mental load following practice because they were sensitive to the time-task constraint, providing researchers a valuable information for a better planning of the mental workload when designed training tasks.


Assuntos
Futebol , Humanos , Olho , Movimentos Sacádicos , Carga de Trabalho , Face
11.
J Clin Med ; 13(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38276141

RESUMO

BACKGROUND: The risk for an unexpected fall can be due to increasing age, health conditions, and loss of cognitive, sensory, or musculoskeletal functions. Falls have personal and economic consequences in many countries. Different disturbances can occur during gait, such as tripping, slipping, or other unexpected circumstances that can generate a loss of balance. The strategies used to recover balance depend on many factors, but selecting a correct response strategy influences the success of balance recovery. OBJECTIVES: (1) To collect and clarify the definitions of compensatory protective step strategies to recover balance in older adults; (2) to identify the most used methods to induce loss of balance; and (3) to identify the most used spatiotemporal variables in analyzing these actions. METHODS: The present review has followed the PRISMA guideline extension for Scoping Review (PRISMA-ScR) and the phases proposed by Askery and O'Malley. The search was conducted in three databases: PubMed, Web of Science, and Scopus. RESULTS: A total of 525 articles were identified, and 53 studies were included. Forty-five articles were quasi-experimental studies, six articles were randomized controlled trials, and two studies had an observational design. In total, 12 compensatory protective step strategies have been identified. CONCLUSIONS: There are 12 compensatory protective step strategies: lowering and elevating strategy, short- and long-step strategy, backward and forward stepping for slip, single step, multiple steps, lateral sidesteps or loaded leg sidestep unloaded leg sidestep, crossover step (behind and front), and medial sidestep. To standardize the terminology applied in future studies, we recommend collecting these strategies under the term of compensatory protective step strategies. The most used methods to induce loss of balance are the tether-release, trip, waist-pull, and slip methods. The variables analyzed by articles are the number of steps, the acceleration phase and deceleration phase, COM displacement, the step initiation or step duration, stance phase time, swing phase time and double-stance duration, stride length, step length, speed step, speed gait and the type of step.

12.
J Clin Med ; 13(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38592707

RESUMO

Background: Previous research has established good test-retest reliability for isokinetic dynamometry in fibromyalgia. However, the reliability of this test under dual-task conditions has not been investigated in fibromyalgia. Methods: A total of 10 women with fibromyalgia participated in this study. Participants completed the concentric/concentric test. The dual-task condition involved subtracting two by two while performing the test. Results: Reliability analysis under the single condition showed "poor" to "excellent" values for maximum peak torque in knee extension and "moderate" to "excellent" values for average. "Poor" to "excellent" reliability values were found in knee flexion for the maximum and average. Dual-task condition in knee extension ranged from "moderate" to "excellent" for maximum and average values, and in knee flexion, it ranged from "poor" to "excellent" for maximum value and from "moderate" to "excellent" for average value. Conclusions: Isokinetic dynamometry demonstrated sufficient reliability for measuring strength in knee extension maximum and average during single-task and dual-task conditions, along with knee flexion dual-task average in fibromyalgia. For knee flexion single-task maximum and average and knee flexion dual-task maximum, we did not obtain sufficiently reliable measurements. Only the concentric/concentric test has been studied, and future studies with a larger sample size are needed in order to generalize the results.

13.
Sci Data ; 11(1): 416, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653806

RESUMO

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.


Assuntos
Cóclea , Animais , Camundongos , Cobaias , Humanos , Ratos , Suínos , Células Ciliadas Auditivas , Microscopia de Fluorescência , Aprendizado de Máquina
14.
Sci Total Environ ; 904: 166368, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619721

RESUMO

Clean technologies are rapidly increasing in the last decade. In the transport sector, market share of global electric car sales has changed from 0.0 % in 2010 to 3.2 % (2.1million) in 2020, and predictions show that sales could reach near 30 % in 2030. This drastic change is mainly encouraged by environmental goals set to reduce greenhouse gas emissions (GHG) expressed in CO2-eq, not emitted by electric vehicles (EVs) during the use phase. However, clean technologies might cause other impacts during manufacture and, while clearly reduce the dependency on oil, can increase the dependency on other materials. In this context, the objectives of our work are quantifying the critical raw materials needed by permanents magnets and batteries of EVs (neodymium, lithium, and cobalt); their supply risk, performing a material flow analysis; and studying their environmental impacts using the methodology "Environmentally-Extended Multi-Regional Input-Output Analysis". This methodology is used to quantify the produced impacts and the country where the impacts are being produced, in contrast to conventional methodologies that only calculate global impacts. Therefore, environmental impacts are estimated considering different scenarios, based on environmental objectives of the European Union and China. In most scenarios China shows a key role in mining and processing of metals, being the country where major impacts are produced. Obtained results are useful to assess which environmental proposals are more effective to reduce the environmental impact of EVs and set the ground to understand the geostrategic importance of key metals used for EVs manufacture.

15.
Front Oncol ; 13: 1157646, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37188190

RESUMO

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups.

16.
Healthcare (Basel) ; 11(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37046945

RESUMO

This study aimed to investigate the concurrent validity between online evaluations (OEs) and face-to-face evaluations (IPEs) of a Senior Fitness Test and two balance tests in people with low back pain (LBP). Forty participants of 58.48 (9.87) years were included. The 30 s chair stand-up, arm curl, 2 min step, chair-sit and reach, back scratch, 8 foot up-and-go, sharpened Romberg, and one-legged stance tests were administrated using both OE and IPE methods. The results indicated no significant differences (p > 0.05) between the two methods except in the 8-foot up-and-go test (p = 0.007). Considering the ICC values and Bland-Altman plots, excellent agreement was found for the chair-sit and reach test, moderate agreement for the arm-curl and 8-foot up-and-go tests, and good agreement for the other tests. Strong correlations (p < 0.001) were observed in all variables except for the arm-curl and 8-foot up-and-go tests, where moderate correlations were found (p < 0.05). These results support the validity of OEs and IPEs in all tests, except for the arm-curl and 8-foot up-and-go tests, where lower ICC values and moderate correlations were found. However, it is important to consider the range of fluctuation of the ICC and the significant values obtained through correlations.

17.
bioRxiv ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37693382

RESUMO

Our sense of hearing is mediated by cochlear hair cells, localized within the sensory epithelium called the organ of Corti. There are two types of hair cells in the cochlea, which are organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains a few thousands of hair cells, and their survival is essential for our perception of sound because they are terminally differentiated and do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. However, the sheer number of cells along the cochlea makes manual quantification impractical. Machine learning can be used to overcome this challenge by automating the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, human, pig and guinea pig cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 90'000 hair cells, all of which have been manually identified and annotated as one of two cell types: inner hair cells and outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to supply other groups within the hearing research community with the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

18.
Clin Neurol Neurosurg ; 219: 107344, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35750020

RESUMO

INTRODUCTION: Previous studies have associated brain abnormalities in people with fibromyalgia with accelerated brain ageing. The prefrontal cortex is located in the anterior pole of the mammalian brain. It is defined as the part of the cerebral cortex that receives projections from the mediodorsal nucleus of the thalamus. AIM: This study aimed to evaluate the volumetric differences in the prefrontal cortex subfields between healthy women and women with fibromyalgia using magnetic resonance imaging (MRI) and controlling for age, estimated intracranial volume, depression, and cognitive impairment. MATERIAL AND METHODS: A total of 47 women with fibromyalgia (recruited from a fibromyalgia local association) and 43 healthy women (retrieved from the Open Access Series of Imaging Studies database) participated in this cross-sectional study. Multiple linear regressions were used to predict the value of the prefrontal cortex subfields as well as to determine if there were volumetric differences between the groups. RESULTS: Volume of all prefrontal cortex regions decreased with each year of age. Healthy women showed higher volume in all the prefrontal cortex subfields than women with fibromyalgia. Regarding partial correlations performed, no significant relation were found between the fibromyalgia impact and the brain volumes analyzed, controlling for depression. CONCLUSIONS: Women with fibromyalgia showed reduced volume in the right caudal middle frontal gyrus, rostral middle frontal gyrus, left inferior frontal gyrus pars opercularis, inferior frontal gyrus pars triangularis, inferior frontal gyrus pars orbitalis, lateral orbitofrontal cortex, right medial orbitofrontal cortex, right rostral anterior cingulate gyrus subfields of the prefrontal cortex and total gray matter compared to healthy women. Furthermore, through an analysis of multiple linear regressions, the left rostral middle frontal gyrus and left lateral orbitofrontal cortex showed significantly volumetric decreases related to depression levels. The total gray matter also shows a significant decrease related to age observed through the analysis of multiple linear regressions. No significant relation were found between the impact of the disease and the brain volumes analyzed, controlling for depression in women with fibromyalgia.


Assuntos
Fibromialgia , Estudos Transversais , Feminino , Fibromialgia/diagnóstico por imagem , Giro do Cíngulo , Humanos , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal/diagnóstico por imagem
19.
Sci Rep ; 12(1): 12616, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35871256

RESUMO

Physical exercise is one of the treatment approaches with the most robust evidence against fibromyalgia (FM) symptoms. This study aimed to investigate the impact of being physically active on the Stroop Color and Word Test (SCWT) performance as well as to investigate and compare the brain electrocortical activity during SCWT. A total of 31 women completed the SCWT while EEG was recorded. People with FM were divided into two groups (physically and non-physically active) according to the WHO guidelines. Furthermore, magnetic resonance imaging was acquired and health-related quality of life, the impact of the disease, and the six-minute walking test were administered. Physically active group showed better performance in the SCWT, exhibiting less error in name different color patches condition (C), more correct responses in named color-word condition (CW) and higher interference score than non-physically active group. Moreover, a significantly higher theta power spectrum in the Fp1 during the condition C in the SCWT and a higher volume in the right rostral middle frontal gyrus have been found in the physically active group. Furthermore, physically active women with FM showed positively correlations between correct responses in names of colors printed in black condition (W) in the SCWT and theta power in the F3, Fz, Fp2 and F4 scalp positions. Regarding non-physically active women with FM, errors in condition CW negatively correlated with the volume of left superior frontal gyrus, left rostral middle frontal gyrus, right rostral middle frontal gyrus, left caudal middle frontal gyrus and right caudal middle frontal gyrus. Furthermore, physically active group showed increased performance in the 6 min walking test and lower disease impact. Fulfil the physical activity recommendation seems to protect brain health since better SCWT performance, greater frontal theta power and higher volume in the right rostral middle frontal gyrus have been found in physically active women with FM.


Assuntos
Encéfalo/fisiologia , Exercício Físico/fisiologia , Fibromialgia/fisiopatologia , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/fisiologia , Qualidade de Vida , Teste de Stroop
20.
J Clin Med ; 12(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36615014

RESUMO

BACKGROUND: Previous studies have reported good test-retest reliability for the 3 m backward test (3MBWT) in different populations. However, reliability of the 3MBWT has not been studied in fibromyalgia (FM) under single and dual-task conditions; Methods: A total of 21 women with FM participated in this study. Participants completed the Revised Fibromyalgia Impact Questionnaire and two physical fitness tests: the 3MBWT and the Timed Up and Go (TUG). The dual-task condition consisted of subtracting two by two while performing the test, starting from a random number less than 100; Results: Values showed that the 3MBWT can be considered reliable under single and dual-task conditions when measured with both a manual stopwatch and a Chronopic automatic stopwatch. A strong concurrent validity was shown of 3MBWT and TUG results in the test and retest and the different devices. The relationship between the performance of the 3MBWT in test and retest conditions under single and dual-task conditions measured with different devices and the impact of the disease were high; Conclusions: The 3MBWT is a reliable tool under the single and dual-task conditions in women with FM. It shows higher reliability values when time is taken using a Chronopic. This test also shows high concurrent validity with the TUG test. Its performance is related to the impact of the disease.

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