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1.
Pacing Clin Electrophysiol ; 47(7): 966-973, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38830778

RESUMEN

BACKGROUND: Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as a predictor of response to cardiac resynchronization therapy (CRT) to reduce nonresponders. AIM: Our study aimed to determine the correlation between the relative change in QRS index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation. METHODS: A three-centers study involving 398 patients with a CRT device was conducted. Clinical, echocardiographic and pharmacological variables, QRSd before and after CRT implantation and QI were measured. RESULTS: In a 6-month follow-up, a significant improvement in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was related to reverse remodeling (multiple r-squared: 0.48, adjusted r-squared: 0.43, p = .001), and the cut-off value that best predicted LV reverse remodeling after 6 months of CRT was 12.25% (AUC 0.7, p = .001). At 24 months, a statistically significant difference was found between patients with a QI ≤ 12.25% and those with a QI > 12.25% regarding NYHA class worsening (p = .04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p = .0179). A correlation between pre-CRT QRSd/LVEDV and QI was observed (r = + 0.20; p = .0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, and LVESV (p < .0001) at follow-up. CONCLUSIONS: QI narrowing after CRT was related to greater echocardiographic reverse remodeling and a lower rate of adverse events (death or cardiovascular hospitalizations). The QI can improve the prediction of adverse events in a population with CRT regardless of comorbidities according to the Charlson Comorbidity Index. QI could be used to predict CRT response.


Asunto(s)
Terapia de Resincronización Cardíaca , Electrocardiografía , Humanos , Masculino , Femenino , Anciano , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Resultado del Tratamiento , Persona de Mediana Edad , Remodelación Ventricular , Pronóstico , Volumen Sistólico , Ecocardiografía
2.
Zygote ; 32(1): 38-48, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38050697

RESUMEN

The actin filaments on the surface of echinoderm oocytes and eggs readily undergo massive reorganization during meiotic maturation and fertilization. In sea urchin eggs, the actin cytoskeletal response to the fertilizing sperm is fast enough to accompany Ca2+ signals and to guide sperm's entry into the egg. Although recent work using live cell imaging technology confirmed changes in the actin polymerization status in fertilized eggs, as was previously shown using light and electron microscopy, it failed to provide experimental evidence of F-actin depolymerization a few seconds after insemination, which is concurrent with the sperm-induced Ca2+ release. In the present study, we applied Raman microspectroscopy to tackle this issue by examining the spectral profiles of the egg's subplasmalemmal regions before and after treating the eggs with actin drugs or fertilizing sperm. At both early (15 s) and late (15 min) time points after fertilization, specific peak shifts in the Raman spectra revealed change in the actin structure, and Raman imaging detected the cytoskeletal changes corresponding to the F-actin reorganization visualized with LifeAct-GFP in confocal microscopy. Our observation suggests that the application of Raman spectroscopy, which does not require microinjection of fluorescent probes and exogenous gene expression, may serve as an alternative or even advantageous method in disclosing rapid subtle changes in the subplasmalemmal actin cytoskeleton that are difficult to resolve.


Asunto(s)
Actinas , Espectrometría Raman , Animales , Masculino , Actinas/metabolismo , Semen , Citoesqueleto de Actina/metabolismo , Fertilización/fisiología , Erizos de Mar/metabolismo , Óvulo/metabolismo
3.
Int J Mol Sci ; 25(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38892201

RESUMEN

This comprehensive review explores the various scenarios of atherosclerosis, a systemic and chronic arterial disease that underlies most cardiovascular disorders. Starting from an overview of its insidious development, often asymptomatic until it reaches advanced stages, the review delves into the pathophysiological evolution of atherosclerotic lesions, highlighting the central role of inflammation. Insights into clinical manifestations, including heart attacks and strokes, highlight the disease's significant burden on global health. Emphasis is placed on carotid atherosclerosis, clarifying its epidemiology, clinical implications, and association with cognitive decline. Prevention strategies, lifestyle modifications, risk factor management, and nuanced antithrombotic treatment considerations are critical to managing cardiovascular complications, thus addressing a crucial aspect of cardiovascular health.


Asunto(s)
Aterosclerosis , Inflamación , Humanos , Aterosclerosis/patología , Aterosclerosis/metabolismo , Inflamación/patología , Factores de Riesgo , Animales
4.
Opt Express ; 31(21): 33945-33962, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37859163

RESUMEN

The growing demand to manipulate objects with long-range techniques has increasingly called for the development of techniques capable of intensifying and spatially concentrating electromagnetic fields with the aim of improving the electromagnetic forces acting on objects. In this context, one of the most interesting techniques is based on the use of plasmonic phenomena that have the ability to amplify and structure the electric field in very small areas. In this paper, we report the simulation analysis of a plasmonic nanostructure useful for optimizing the profile of the induced plasmonic field distribution and thus the motion dynamics of a nanoparticle, overcoming some limitations observed in the literature for similar structures. The elementary cell of the proposed nanostructure consists of two gold scalene trapezoids forming a planar V-groove. The spatial replication of this elementary cell to form linear or circular array sequences is used to improve the final nanoparticle velocity. The effect of the geometry variation on the plasmonic behaviour and consequently on the force generated, was analyzed in detail. The results suggest that this optimized plasmonic structure has the potential to efficiently propel macroscopic objects, with implications for various fields such as aerospace and biomedical research.

5.
Pacing Clin Electrophysiol ; 46(3): 268-270, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36269180

RESUMEN

Leadless pacemaker (LPs) is a safe device and the implantation rates of this device is increasing. The device extraction and replacement are today a challenging procedures especially in case of infections, fragile and older patients or in unfavorable venous anatomy; LPs can be a valid alternative strategy in these cases. We report a case of management of a patient with multiple previous device replacements and extractions, with malfunction of transvenous pacemaker and with a fibrous membrane between the walls of the ventricular lead and the superior vena cava (SVC), who underwent a successful LP implantation.


Asunto(s)
Estimulación Cardíaca Artificial , Marcapaso Artificial , Humanos , Estimulación Cardíaca Artificial/métodos , Vena Cava Superior , Lipopolisacáridos , Resultado del Tratamiento
6.
Hematol Oncol ; 40(5): 835-842, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35667043

RESUMEN

Measurable residual disease (MRD) has emerged as a relevant parameter of response to therapy in chronic lymphocytic leukemia (CLL). Although several methods have been developed, flow cytometry has emerged as the most useful and standardized approach to measure and quantify MRD. The improved sensitivity of MRD measurements has been paralleled by the development of more effective therapeutic strategies for CLL, increasing the applicability of MRD detection in this setting. Chemotherapy and chemoimmunotherapy have firstly demonstrated their ability to obtain a deep MRD. Combined targeted therapies are also demonstrating a high molecular response rate and prospective trials are exploring the role of MRD to guide the duration of treatment in this setting. In this review we briefly summarize what we have learned about MRD with emphasis on its flow cytometric detection.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Citometría de Flujo , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/terapia , Estudios Prospectivos
7.
Eur J Clin Pharmacol ; 78(1): 19-25, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34554274

RESUMEN

PURPOSE: Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. METHODS: This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. RESULTS: A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11-13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p < 0.001), and from 29 to 82% in group B (p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. CONCLUSION: One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B.


Asunto(s)
Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Valsartán/uso terapéutico , Anciano , Aminobutiratos/administración & dosificación , Aminobutiratos/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/efectos adversos , Presión Sanguínea/efectos de los fármacos , Comorbilidad , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico/efectos de los fármacos , Valsartán/administración & dosificación , Valsartán/efectos adversos , Función Ventricular Izquierda/efectos de los fármacos , Prueba de Paso
8.
Nutr Metab Cardiovasc Dis ; 31(7): 2144-2150, 2021 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-34053832

RESUMEN

BACKGROUND AND AIMS: In the present study, we aimed to compare the clinical and coronary angiography features between South Asian and Caucasian patients with Acute Coronary Syndrome (ACS). In particular, we focused our analysis on the evaluation of recent cardiovascular risk markers, such as remnant cholesterol, corresponding to all plasma cholesterol minus HDL-C (high-density lipoprotein cholesterol) and LDL-C (low-density lipoprotein cholesterol), and the Monocyte-to-HDL-cholesterol ratio. We also compared values of several lipoprotein ratios and the Platelet-to-lymphocyte ratio, accurate predictors of coronary events and coronary artery disease. METHODS AND RESULTS: We recruited 40 South Asian and 40 Caucasian patients admitted for ACS. Data were collected by consulting patients' medical records. We used Chi-square test and Student's t-test to analyse qualitative and quantitative variables, respectively. South Asian patients, compared to Caucasians, showed higher mean values of the parameters analysed: remnant cholesterol (32.6 ± 17 vs 26.5 ± 9.6), Monocyte-to-HDL-cholesterol ratio (26.4 ± 48.7 vs 16.5 ± 8.3), Platelet-to-lymphocyte ratio (124.7 ± 130.7 vs 120.5 ± 58.8). Moreover, higher mean values of several lipoprotein ratios were also found in South Asian patients compared to the control group. However, statistical significance was not reached for any of these differences observed. CONCLUSIONS: The evaluation of the parameters analysed in this study might provide accurate information regarding the cardio-metabolic risk in South Asian patients. However, further studies with larger samples are needed to obtain more significant results.


Asunto(s)
Síndrome Coronario Agudo/etnología , Pueblo Asiatico , HDL-Colesterol/sangre , Colesterol/sangre , Enfermedad de la Arteria Coronaria/etnología , Monocitos , Población Blanca , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico por imagen , Adulto , Biomarcadores/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Italia/epidemiología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Estudios Retrospectivos , Medición de Riesgo
9.
Opt Express ; 27(13): 18776-18786, 2019 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-31252814

RESUMEN

In this work, we investigate the evanescent field sensing mechanism provided by an all-dielectric metasurface supporting bound states in the continuum (BICs). The metasurface is based on a transparent photonic crystal with subwavelength thickness. The BIC electromagnetic field is localized along the direction normal to the photonic crystal nanoscale-thin slab (PhCS) because of a topology-induced confinement, exponentially decaying in the material to detect. On the other hand, it is totally delocalized in the PhCS plane, which favors versatile and multiplexing sensing schemes. Liquids with different refractive indices, ranging from 1.33 to 1.45, are infiltrated in a microfluidic chamber bonded to the sensing dielectric metasurface. We observe an experimental exponential sensitivity leading to differential values as large as 226 nm/RIU with excellent FOM. This behavior is explained in terms of the physical superposition of the field with the material under investigation and supported by a thorough numerical analysis. The mechanism is then translated to the case of molecular adsorption where a suitable theoretical engineering of the optical structure points out potential sensitivities as large as 4000 nm/RIU.

10.
Medicina (Kaunas) ; 55(10)2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31574989

RESUMEN

Atrial fibrillation the most common cardiac arrhythmia. Its incidence rises steadily with each decade, becoming a real "epidemic phenomenon". Cardioversion is defined as a rhythm control strategy which, if successful, restores normal sinus rhythm. This, whether obtained with synchronized shock or with drugs, involves a periprocedural risk of stroke and systemic embolism which is reduced by adequate anticoagulant therapy in the weeks before or by the exclusion of left atrial thrombi. Direct oral anticoagulants are safe, manageable, and provide rapid onset of oral anticoagulation; they are an important alternative to heparin/warfarin from all points of view, with a considerable reduction in bleedings and increase in the safety and quality of life of patients.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Cardioversión Eléctrica , Administración Oral , Anticoagulantes/administración & dosificación , Esquema de Medicación , Humanos
11.
Reprod Biol Endocrinol ; 16(1): 117, 2018 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-30594197

RESUMEN

Air pollution is a cause of concern for human health. For instance, it is associated with an increased risk for cancer, cardiovascular and respiratory disorders. In vitro and in vivo studies suggested that air pollutants could act as endocrine disruptors, promote oxidative stress and exert genotoxic effect. Whether air pollution affects female infertility is under debate. The aim of the present study was to conduct a systematic review of studies that evaluated the impact of air pollution on female infertility. We systematically searched the MEDLINE (PubMed) and SCOPUS databases to identify all relevant studies published before October 2017. No time or language restrictions were adopted, and queries were limited to human studies. We also hand-searched the reference lists of relevant studies to ensure we did not miss pertinent studies. The risk of bias and quality assessment of the studies identified were performed using the Newcastle-Ottawa Scale. Primary outcomes were conception rate after spontaneous intercourse and live birth rate after in vitro fertilization (IVF) procedures. Secondary outcomes were first trimester miscarriage, stillbirths, infertility, number of oocytes and embryo retrieved. Eleven articles were included in the analysis. We found that in the IVF population, nitrogen dioxide and ozone were associated with a reduced live birth rate while particulate matter of 10 mm was associated with increased miscarriage. Furthermore, in the general population, particulate matter of 2.5 mm and between 2.5 and 10 mm were associated with reduced fecundability, whereas sulfur dioxide, carbon monoxide and nitrogen dioxide might promote miscarriage and stillbirths. The main limitation of our findigns resides in the fact that the desegn of studies included are observational and retrospective. Furthermore, there was a wide heterogenity among studies. Although larger trials are required before drawing definitive conclusions, it seems that air pollution could represent a matter of concern for female infertility.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Fertilidad/fisiología , Infertilidad Femenina/etiología , Aborto Espontáneo/inducido químicamente , Tasa de Natalidad , Femenino , Fertilización In Vitro , Humanos , Nacimiento Vivo
12.
Sensors (Basel) ; 18(11)2018 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-30400282

RESUMEN

This paper presents the design, fabrication, and characterization of Schottky erbium/silicon photodetectors working at 1.55 µm. These erbium/silicon junctions are carefully characterized using both electric and optical measurements at room temperature. A Schottky barrier ΦB of ~673 meV is extrapolated; the photodetectors show external responsivity of 0.55 mA/W at room temperature under an applied reverse bias of 8 V. In addition, the device performance is discussed in terms of normalized noise and noise-equivalent power. The proposed devices will pave the way towards the development of Er-based photodetectors and light sources to be monolithically integrated in the same silicon substrate, and both operating at 1.55 µm.

14.
Sensors (Basel) ; 16(8)2016 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-27548187

RESUMEN

Microfluidic technology allows to realize devices in which cells can be imaged in their three-dimensional shape. However, there are still some limitations in the method, due to the fact that cells follow a straight path while they are flowing in a channel. This can result in a loss in information, since only one side of the cell will be visible. Our work has started from the consideration that if a cell rotates, it is possible to overcome this problem. Several approaches have been proposed for cell manipulation in microfluidics. In our approach, cells are controlled by only taking advantages of hydrodynamic forces. Two different devices have been designed, realized, and tested. The first device induces cell rotation in a plane that is parallel (in-plane) to the observation plane, while the second one induce rotation in a plane perpendicular (out-of-plane) to the observation plane.

15.
Int J Mol Sci ; 17(10)2016 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-27690008

RESUMEN

The frustule of diatoms, unicellular microalgae, shows very interesting photonic features, generally related to its complicated and quasi-periodic micro- and nano-structure. In order to simulate light propagation inside and through this natural structure, it is important to develop three-dimensional (3D) models for synthetic replica with high spatial resolution. In this paper, we present a new method that generates images of microscopic diatoms with high definition, by merging scanning electron microscopy and digital holography microscopy or atomic force microscopy data. Starting from two digital images, both acquired separately with standard characterization procedures, a high spatial resolution (Δz = λ/20, Δx = Δy ≅ 100 nm, at least) 3D model of the object has been generated. Then, the two sets of data have been processed by matrix formalism, using an original mathematical algorithm implemented on a commercially available software. The developed methodology could be also of broad interest in the design and fabrication of micro-opto-electro-mechanical systems.

17.
Radiol Med ; 120(2): 190-205, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25030969

RESUMEN

To date, several clinical and multicentre studies have demonstrated the accuracy of perfusion cardiac magnetic resonance to detect ischaemia in comparison with quantitative coronary angiography, other noninvasive diagnostic techniques (single photon emission computed tomography; positron-emission tomography), and invasive haemodynamic measurements (fractional flow reserve). Moreover, the favourable safety profile and increasing availability contribute to make perfusion cardiac magnetic resonance one of the modalities of choice for the detection of myocardial ischaemia. Recently, the first evidence of the prognostic value of perfusion cardiac magnetic resonance results has also become available. This review summarises the technical and interpretation key points of perfusion cardiac magnetic resonance scan, the clinical indications, the most recent available literature about its diagnostic performance and prognostic value, and how perfusion cardiac magnetic resonance compares with other noninvasive techniques.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Imagen por Resonancia Magnética , Imagen de Perfusión Miocárdica , Enfermedad de la Arteria Coronaria/fisiopatología , Circulación Coronaria , Árboles de Decisión , Gadolinio , Humanos , Reproducibilidad de los Resultados , Tomografía Computarizada de Emisión de Fotón Único
18.
Nanomaterials (Basel) ; 14(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38786786

RESUMEN

Spin-orbit coupling in nanoscale optical fields leads to the emergence of a nontrivial spin angular momentum component, transverse to the orbital momentum. In this study, we initially investigate how this spin-orbit coupling effect influences the dynamics in gold monomers. We observe that localized surface plasmon resonance induces self-generated transverse spin, affecting the trajectory of the nanoparticles as a function of the incident polarization. Furthermore, we investigate the spin-orbit coupling in gold dimers. The resonant spin momentum distribution is characterized by the unique formation of vortex and anti-vortex spin angular momentum pairs on opposite surfaces of the nanoparticles, also affecting the particle motion. These findings hold promise for various fields, particularly for the precision control in the development of plasmonic thrusters and the development of metasurfaces and other helicity-controlled system aspects. They offer a method for the development of novel systems and applications in the realm of spin optics.

19.
J Basic Clin Physiol Pharmacol ; 35(1-2): 93-97, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38015811

RESUMEN

OBJECTIVES: Meckel's diverticulum (MD) is a common asymptomatic congenital intestinal anomaly. Clinical manifestations of MD can occur in about 4 % of cases by the presentation of its complications, generally intestinal occlusion, bleeding, and diverticular inflammation. MD's complications are challenging preoperative diagnoses, as manifest with clinical symptoms that overlap with those of other acute non-traumatic abdominal diseases. Thus, in the emergency setting, abdominal computed tomography (CT) represents an essential tool for the correct diagnosis of complicated MD. CASE PRESENTATION: We present a case of a preoperative CT diagnosis of perforated Meckel's diverticulitis in a young patient admitted to our Emergency Department complaining of acute abdominal pain. CONCLUSIONS: The case highlights the importance of evaluating Meckel's diverticulum complications among the differential diagnoses of acute non-traumatic abdominal pain and the high sensitivity of CT in assessing their presence in the proper clinical setting.


Asunto(s)
Diverticulitis , Divertículo Ileal , Humanos , Divertículo Ileal/diagnóstico , Divertículo Ileal/diagnóstico por imagen , Dolor Abdominal/etiología , Dolor Abdominal/complicaciones , Diverticulitis/diagnóstico por imagen , Diverticulitis/cirugía , Tomografía Computarizada por Rayos X/efectos adversos , Diagnóstico Diferencial , Enfermedad Aguda
20.
NPJ Microgravity ; 10(1): 16, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341423

RESUMEN

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap "Biology in Space and Analogue Environments" focusing on "How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?" The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed.

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