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1.
BMJ Neurol Open ; 6(1): e000582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618151

RESUMO

Background: Essential tremor (ET) is a movement disorder that affects 4%-5% of adults >65 years. For patients with medically refractory ET, neurosurgical interventions such as deep brain stimulation (DBS) and unilateral MR-guided focused ultrasound thalamotomy (MRgFUS) are available. In this retrospective cohort study, we examined the demographics of patients with ET who have received MRgFUS and evaluated trends in DBS usage in the USA after the introduction of MRgFUS in 2016. Methods: We used multiple databases to examine the demographics of patients who received DBS and MRgFUS, and trends in DBS. To assess the demographics, we queried the TriNetX database from 2003 to 2022 to identify patients diagnosed with ET and stratify them by DBS or MRgFUS treatment by using Current Procedural Terminology codes. Patient demographics were reported as frequencies and percentages. To examine the trends in DBS for ET, the yearly frequency of DBS procedures done for ET between 2012 and 2019 was extracted from the National Inpatient Sample (NIS) database, and breakpoint analysis was performed. Additionally, the yearly frequency of MRgFUS procedures for ET was obtained from Insightec Exlabate. Results: Most of the patients (88.69%) in the cohort extracted from TriNetX database self-identified as white, followed by black or African American (2.40%) and Asian (0.52%). A higher percentage of black patients received MRgFUS treatment than DBS (4.10% vs 1.88%). According to the NIS database, from 2012 to 2020, 13 525 patients received DBS for ET. Conclusion: This study provides an overview of the characteristics of patients who undergo DBS or MRgFUS. We found notable differences in sex and race among patients who underwent each treatment type. Additionally, until at least the beginning of 2020, the number of DBS procedures for ET was not negatively affected after the introduction of MRgFUS.

2.
Clin Auton Res ; 34(1): 117-124, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429568

RESUMO

PURPOSE: We investigated the effect of levodopa on postural blood pressure changes in individuals with Parkinson disease (PD) with (PD+OH) and without neurogenic OH (PD-OH). METHODS: We performed a prospective randomized crossover study with autonomic testing performed ON and OFF levodopa. The primary outcome was the change in systolic blood pressure (SBP) from supine to 70° tilt at 3 min (ΔSBP-3'). Secondary outcomes included indices of baroreflex function and blood pressure and heart rate during tilt. RESULTS: We enrolled 40 individuals with PD (21 PD+OH, 19 PD-OH), mean age (SD) 73.2 years (7.9), 13 women (32.5%)). There was no difference in age, sex, disease duration, and severity between PD+OH and PD-OH. Mean difference in ΔSBP-3' ON versus OFF levodopa in the whole study population was - 3.20 mmHg [- 7.36 to 0.96] (p = 0.14). Mean difference in ΔSBP-3' was - 2.14 mmHg [- 7.55 to 3.28] (p = 0.45) in PD+OH and - 5.14 mmHg [- 11.63 to 1.35] (p = 0.14) in PD-OH. Mean difference in ΔSBP ON versus OFF levodopa was greater at 7 and 10 min (- 7.52 mmHg [- 11.89 to - 3.15], p = 0.002, and - 7.82 mmHg [- 14.02 to - 1.67], p = 0.02 respectively). Levodopa was associated with lower absolute values of blood pressure in both PD+OH and PD-OH and cardiovascular noradrenergic baroreflex impairment. CONCLUSION: Levodopa decreases blood pressure in both PD with and without autonomic failure, but it does not cause a greater fall in blood pressure from supine to standing at 3 min. Levodopa-induced baroreflex sympathetic noradrenergic impairment may contribute to lower blood pressure. Lower standing blood pressure with levodopa may increase the risks of fall and syncope.


Assuntos
Hipotensão Ortostática , Doença de Parkinson , Humanos , Feminino , Idoso , Levodopa/farmacologia , Levodopa/uso terapêutico , Doença de Parkinson/complicações , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Hipotensão Ortostática/complicações , Estudos Prospectivos , Norepinefrina
3.
J Colloid Interface Sci ; 662: 446-459, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364470

RESUMO

Lipid nanoparticles own a remarkable potential in nanomedicine, only partially disclosed. While the clinical use of liposomes and cationic lipid-nucleic acid complexes is well-established, liquid lipid nanoparticles (nanoemulsions), solid lipid nanoparticles, and nanostructured lipid carriers have even greater possibilities. However, they face obstacles in being used in clinics due to a lack of understanding about the molecular mechanisms controlling their drug loading and release, interactions with the biological environment (such as the protein corona), and shelf-life stability. To create effective drug delivery carriers and successfully translate bench research to clinical settings, it is crucial to have a thorough understanding of the internal structure of lipid nanoparticles. Through synchrotron small-angle X-ray scattering experiments, we determined the spatial distribution and internal structure of the nanoparticles' lipid, surfactant, and the bound water in them. The nanoparticles themselves have a barrel-like shape that consists of coplanar lipid platelets (specifically cetyl palmitate) that are covered by loosely spaced polysorbate 80 surfactant molecules, whose polar heads retain a large amount of bound water. To reduce the interface cost of bound water with unbound water without stacking, the platelets collapse onto each other. This internal structure challenges the classical core-shell model typically used to describe solid lipid nanoparticles and could play a significant role in drug loading and release, biological fluid interaction, and nanoparticle stability, making our findings valuable for the rational design of lipid-based nanoparticles.


Assuntos
Lipossomos , Nanopartículas , Raios X , Nanopartículas/química , Portadores de Fármacos/química , Tensoativos/química , Lipídeos/química , Água/química , Tamanho da Partícula
4.
J Neural Eng ; 21(1)2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38335553

RESUMO

Objective: Transcranial focused low-intensity ultrasound has the potential to noninvasively modulate confined regions deep inside the human brain, which could provide a new tool for causal interrogation of circuit function in humans. However, it has been unclear whether the approach is potent enough to modulate behavior.Approach: To test this, we applied low-intensity ultrasound to a deep brain thalamic target, the ventral intermediate nucleus, in three patients with essential tremor.Main results: Brief, 15 s stimulations of the target at 10% duty cycle with low-intensity ultrasound, repeated less than 30 times over a period of 90 min, nearly abolished tremor (98% and 97% tremor amplitude reduction) in 2 out of 3 patients. The effect was observed within seconds of the stimulation onset and increased with ultrasound exposure time. The effect gradually vanished following the stimulation, suggesting that the stimulation was safe with no harmful long-term consequences detected.Significance: This result demonstrates that low-intensity focused ultrasound can robustly modulate deep brain regions in humans with notable effects on overt motor behavior.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial , Humanos , Tremor Essencial/terapia , Tremor/terapia , Tálamo/diagnóstico por imagem , Encéfalo , Resultado do Tratamento
5.
Sci Rep ; 14(1): 4238, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378777

RESUMO

Creep failure of hierarchical materials is investigated by simulation of beam network models. Such models are idealizations of hierarchical fibrous materials where bundles of load-carrying fibers are held together by multi-level (hierarchical) cross-links. Failure of individual beams is assumed to be governed by stress-assisted thermal activation over local barriers, and beam stresses are computed by solving the global balance equations of linear and angular momentum across the network. Disorder is mimicked by a statistical distribution of barrier heights. Both initially intact samples and samples containing side notches of various length are considered. Samples with hierarchical cross-link patterns are simulated alongside reference samples where cross-links are placed randomly without hierarchical organization. The results demonstrate that hierarchical patterning may strongly increase creep strain and creep lifetime while reducing the lifetime variation. This is due to the fact that hierarchical patterning induces a failure mode that differs significantly from the standard scenario of failure by nucleation and growth of a critical crack. Characterization of this failure mode demonstrates good agreement between the present simulations and experimental findings on hierarchically patterned paper sheets.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38376460

RESUMO

BACKGROUND: Pediatric continence dysfunction is not uncommon. It causes long-term disability, impairing quality of life, activities and relationships with pears and can affect until adulthood. A high-risk population are children with Hirschsprung's disease and congenital anorectal malformation. Conservative medical and surgical management of continence dysfunction in this population is deeply described, while the rehabilitation issues are still unexplored. Aim of this study is to preliminary verify the feasibility, tolerance and effectiveness of an intensive technological aided and individualized pelvic floor rehabilitation program for pediatric patients. METHODS: This is a single-center, retrospective observational study. The assessment was performed by collecting demographic data, general and local physical examination and scoring assessment tools (Rintala Continence Score and Wexner Score). The study was conducted in the Rehabilitation Unit of the pediatric Giannina Gaslini Institute, a tertiary care pediatric hospital in Genoa (Italy) between September 2015 to August 2019. We enrolled 31 children; 25 male (80.6%) and six females (19%), aged between 5 and 14 years (mean age 9 years) at the beginning of the training. Twenty children (65.5%) had Hirschsprung's disease, and 11 children (34.5%) had a congenital anorectal malformation. The rehabilitation training program was customized on the compromised function, the anatomic characteristics, the child's age and compliance. The training was aimed at improving tone, strength, endurance of the pelvic floor, compliance and rectal sensitivity, and also the frequency of the bowel movements. All patients enrolled in the study underwent an intensive outpatient treatment lasted 5 days for children older than 7 years; 10 days for younger. The intensive rehabilitation treatment was followed by a continuous home training program. RESULTS: Twenty-nine children (96.8%) completed the training. A global improvement is observed in continence functioning in all the cohort at T1 (P<0.0001), maintained at T3 (P<0.0001) at both Rintala Continence Score and Wexner Score. No adverse effects have been referred. CONCLUSIONS: Our specific pediatric training program for pelvic floor rehabilitation is effective and safe for children with continence dysfunctions after pelvic surgery due to Hirschsprung's disease and anorectal malformations. The continence rehabilitation multimodal program should be integrated in the care of children with continence dysfunctions. It cooperates in the prevention of the long-term health global impairment and also in the reduction of social economic effort.

7.
Clin Neuropsychol ; 38(1): 150-163, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974932

RESUMO

Objective: Essential tremor (ET), while defined by progressive motor symptoms, is increasingly associated with cognitive impairments (e.g. attention, memory, and executive functions). This study characterizes the cognitive profile of individuals with ET on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a commonly-used neuropsychological screening measure. Method: Seventy-seven individuals (mean age: 70.6, 34% female) diagnosed with ET and being considered for surgical/procedural intervention were recruited from a Movement Disorders Clinic. All participants completed the RBANS, Grooved Pegboard Test (GPB), and Fahn, Tolosa, Marin Tremor Scale (FTMTS) in the clinical evaluation of their tremor. Results: One-sample t-tests found Immediate Memory, Language, Attention, and Total Scale Index scores to be significantly lower than the expected population mean (p < .05). List Learning, Semantic Fluency, Coding, and List Recall subtests were significantly lower and Picture Naming was significantly higher than the expected population mean (p < .05). GPB scores were correlated with the Attention Index as well as List Learning and Coding subtests. FTMTS Severity was correlated with the Coding subtest and FTMTS Disability was correlated with the Figure Recall subtest. Conclusions: Results support prior literature indicating cognitive weaknesses in those with ET. Individuals with ET had poorer global cognitive abilities, with specific decrements in Immediate Memory, Attention, and Language. Notably, the Attention Index and Coding subtest were most affected by motor functioning. Cognitive screening measures, like the RBANS, can efficiently identify strengths and weaknesses in individuals with ET seeking surgical/procedural interventions.


Assuntos
Transtornos Cognitivos , Tremor Essencial , Humanos , Feminino , Idoso , Masculino , Transtornos Cognitivos/diagnóstico , Tremor Essencial/diagnóstico , Tremor Essencial/complicações , Tremor/complicações , Testes Neuropsicológicos , Cognição
8.
Orphanet J Rare Dis ; 18(1): 392, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124110

RESUMO

BACKGROUND: Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) is an autosomal dominant disease with increased bone reabsorption in the carpus and tarsus and the elbows, knees and spine. The disease is extremely heterogeneous and secondary and tertiary injuries vary widely and can lead to progressive disability and severe functional limitations. In addition to the available and upcoming drug therapies, physical medicine and rehabilitation are important treatment options. Currently, the indication and plan are overlooked, nonspecific and reported only for one patient. METHODS: We describe a case series of MCTO patients diagnosed and followed by a centre to identify functional deficit as a potential clinical marker of disease progression for future etiological therapies. In addition, we define a symptomatic treatment approach and specific clinical management, including a patient-centred rehabilitation approach. Functional assessments are performed independently by a multidisciplinary group to establish the functional abilities of patients and the relationship between residual motor skills and their degree of autonomy and participation. We suggest a way to identify a rehabilitation plan based on a specific disease using the International Classification of Functioning, Disability and Health Children and Youth (ICF-CY). RESULTS: To define a reliable and reproducible "Function Profile", through age and over time, we used to value the disease status according to the ICF-CY domains. It could be used to determine the complexity of the illness, its overall impact on the complexity of the person and the burden on the caregiver, and an eventual short- and long-term rehabilitation plan for MCTO and other ultra-rare diseases. CONCLUSION: Based on the MCTO experience, we suggest a way to determine a rehabilitation plan based on a specific disease and patient needs, keeping in mind that often the final point is not recovering the full function but improving or maintaining the starting point. In all cases, each patient at the time of diagnosis requires a functional assessment that must be repeated over time to adjust the course of rehabilitation. The evaluations revealed the importance of early rehabilitation management in enhancing independence, participation and control of stress deconditioning, shrinking of muscle tendons and loss of movement to immobility.


Assuntos
Síndrome de Hajdu-Cheney , Osteólise , Criança , Adolescente , Humanos , Osteólise/diagnóstico , Atividades Cotidianas , Progressão da Doença
9.
J Clin Exp Neuropsychol ; 45(8): 786-797, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37728425

RESUMO

INTRODUCTION: Within clinical neuropsychology, a classic diagnostic distinction is made between cortical and subcortical disorders, especially based on their memory profiles. Typically, this is based on the comparison of recall and recognition trials, where individuals with cortical conditions do not tend to benefit (i.e., score well) on recognition trials and individuals with subcortical conditions do. Although the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a widely used brief cognitive battery, there is a lack of evidence to support this measure's utility in distinguishing between the memory profiles of these conditions. METHOD: Thirty-six mild Alzheimer's disease (AD), 55 Parkinson's disease (PD), and 105 essential tremor (ET) participants (N = 196) were administered the RBANS with additional Story and Figure Recognition subtests. Group differences on recall and recognition scores (Total Correct, Hits or True Positives, False Positive Errors, and discriminability index) were examined across the three groups, while controlling for the influence of age and gender. RESULTS: As expected, individuals with AD had poorer recognition scores compared to the other clinical groups across tasks (all p-values < .05), while the ET sample largely performed comparably to the PD sample. With the exception of comparable Figure Recognition and Recall in the PD sample, all groups exhibited significantly greater recognition Hit performance compared to Recall (all p-values < .05). CONCLUSIONS: The group differences in performance across RBANS recognition subtests suggest support for traditional "cortical" and "subcortical" profiles. However, all groups, including the mild AD sample, demonstrated a benefit from recognition cues compared to free recall. Overall, these findings support the inclusion of the newly developed Story and Figure Recognition subtests in future clinical practice and research endeavors.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Humanos , Reconhecimento Psicológico , Rememoração Mental , Doença de Alzheimer/diagnóstico , Sinais (Psicologia)
10.
Clin Neurol Neurosurg ; 233: 107949, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37703618

RESUMO

BACKGROUND: Intrathecal baclofen therapy (ITB) is an effective treatment for reducing spasticity but can be associated with various complications, including infection and implant malfunction. METHODS: This retrospective cohort study analyzed refill reports, complications, and functional outcomes in 40 consecutive patients with intractable spasticity or dystonia undergoing ITB. RESULTS: Among the 40 patients, 8 experienced complications, including two cases of calcification of the baclofen pump pouch and surrounding tissue, a rare complication not extensively described in the literature. DISCUSSION: Calcification, in addition to port access difficulties, could lead to drug delivery failure. We hypothesize that calcification may result from microtrauma or needlestick injury to the subcutaneous tissue and muscle fascia. The length of time the pump stays in the pocket could also contribute to favoring this phenomenon. CONCLUSION: As the number of patients receiving ITB increases, physicians must be aware of potential life-threatening complications. The risk of pouch calcification should be further investigated and considered in managing patients undergoing ITB, as it could significantly impact patient care.

11.
Stereotact Funct Neurosurg ; 101(5): 314-318, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37690446

RESUMO

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies. METHODS: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. RESULTS: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. CONCLUSION: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.


Assuntos
Tremor Essencial , Doença de Parkinson , Humanos , Feminino , Idoso , Masculino , Tremor , Estudos Prospectivos , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/cirurgia , Imageamento por Ressonância Magnética/métodos , Anticoagulantes/efeitos adversos , Espectroscopia de Ressonância Magnética , Resultado do Tratamento
12.
Nanoscale ; 15(37): 15196-15205, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37624640

RESUMO

Guanine (G) hydrogels are very attractive materials made by the supramolecular organization of G-derivatives in water. In this paper, hydrogels composed of guanosine 5'-monophosphate (GMP) and guanosine (Gua), that make long, flexible and knotted G-quadruplexes, were investigated by small- and wide-angle X-ray scattering (SAXS and WAXS) to comprehend the origin of their unique orientational properties. The SAXS intensity, analysed at a fixed scattering vector modulus Q as a function of polar angle, allowed us to derive the Maier-Saupe orientation parameter m. The strong dependence of m on hydrogel composition and temperature demonstrated that the preferred orientation is controlled by the quadruplex surface charge and flexibility. Indeed, a possible correlation between the orientation parameter m and the quadruplex-to-quadruplex lateral interactions was explored. Results confirmed that the balance between attractive and repulsive interactions plays a main role in the orientational anisotropy: quadruplex clusters lose their orientational properties when attractive interactions decrease. The key role of the number of negative charges per unit length of the G-quadruplex filaments was confirmed by Atomic Force Microscopy (AFM) observations. Indeed, directionality histograms showed that in the presence of a large amount of Gua, G-quadruplexes follow preferential orientations other than those related to the strong interactions with the K+ pattern on the mica surface. The fact that lateral quadruplex-to-quadruplex interactions, even in the presence of external (opposing) forces, can tune the hydrogel alignment in a given preferred direction provides novel possibilities for scaffold/3D printing applications.

13.
Biomol Concepts ; 14(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37542518

RESUMO

The study of the interaction between lipid membranes and amyloidogenic peptides is a turning point for understanding the processes involving the cytotoxicity of peptides involved in neurodegenerative diseases. In this work, we perform an experimental study of model membrane-lysozyme interaction to understand how the formation of amyloid fibrils can be affected by the presence of polar and zwitterionic phospholipid molecules (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol [POPG]). The study was conducted above and below the critical micellar concentration (CMC) using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-Vis spectrophotometry, and the quartz crystal microbalance (QCM). Our results show that the presence of phospholipids appears to be a factor favoring the formation of amyloid aggregates. Spectrophotometric and DLS data revealed that the quantity of ß -structure increases in the presence of POPG and POPC at different concentrations. The presence of POPG and POPC increases the speed of the nucleation process, without altering the overall structures of the fibrillar final products.


Assuntos
Bicamadas Lipídicas , Muramidase , Bicamadas Lipídicas/química , Amiloide , Peptídeos
14.
J Colloid Interface Sci ; 645: 448-457, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37156153

RESUMO

HYPOTHESIS: Modification of polyallylamine hydrochloride (PAH) with heterobifunctional low molecular weight polyethylene glycol (PEG) (600 and 1395 Da), and subsequent attachment of mannose, glucose, or lactose sugars to PEG, can lead to formation of polyamine phosphate nanoparticles (PANs) with lectin binding affinity and narrow size distribution. EXPERIMENTS: Size, polydispersity, and internal structure of glycosylated PEGylated PANs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). Fluorescence correlation spectroscopy (FCS) was used to study the association of labelled glycol-PEGylated PANs. The number of polymer chains forming the nanoparticles was determined from the changes in amplitude of the cross-correlation function of the polymers after formation of the nanoparticles. SAXS and fluorescence cross-correlation spectroscopy were used to investigate the interaction of PANs with lectins: concanavalin A with mannose modified PANs, and jacalin with lactose modified ones. FINDINGS: Glyco-PEGylated PANs are highly monodispersed, with diameters of a few tens of nanometers and low charge, and a structure corresponding to spheres with Gaussian chains. FCS shows that the PANs are single chain nanoparticles or formed by two polymer chains. Concanavalin A and jacalin show specific interactions for the glyco-PEGylated PANs with higher affinity than bovine serum albumin.


Assuntos
Nanopartículas , Fosfatos , Concanavalina A , Lactose , Manose , Espalhamento a Baixo Ângulo , Raios X , Polietilenoglicóis/química , Difração de Raios X , Nanopartículas/química , Poliaminas , Lectinas/química , Polímeros , Análise Espectral
15.
Front Plant Sci ; 14: 1143998, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056507

RESUMO

Diatoms represent the most abundant and diversified class of primary producers in present oceans; their distinctive trait is the ability to incorporate silicic acid in a silica outer shell called frustule. Numerous adaptative functions are ascribed to frustules, including the control of vertical movements through the water column; this indirectly determines cell access to fundamental resources such as light and nutrients, and favors diatom escape from predators. At the same time, light guides phototroph movements in the water column by affecting cell density (e.g., by modulating Si deposition in diatoms, vacuole volume, and/or solution). We investigated how the tremendous diversity in morphology and silicification that characterizes the frustule and the crucial role of light in diatom spatial distribution govern diatom sinking capacity. To test their integrative effects, we acclimated four diatoms distinguished by frustule traits (Chaetoceros muelleri, Conticribra weissflogii, Phaeodactylum tricornutum, and Cylindrotheca fusiformis) to different light conditions and evaluated their physiological performance in terms of growth, elemental composition, morphological changes, and their in vivo sinking capacity. What emerged from this study was that silicification, more than other morphological characteristics, controls species vertical movements, while a higher energy availability enhances cell floating independently from the silica content.

16.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047038

RESUMO

The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruses. Like SARS-CoV and MERS-CoV, the mature and active form of SARS-CoV-2 Mpro is a dimer composed of identical subunits, each with a single active site. Individual monomers, however, have very low or no catalytic activity. As such, inhibition of Mpro can be achieved by molecules that target the substrate binding pocket to block catalytic activity or target the dimerization process. In this study, we investigated GC376, a transition-state analog inhibitor of the main protease of feline infectious peritonitis coronavirus, and Nirmatrelvir (NMV), an oral, bioavailable SARS-CoV-2 Mpro inhibitor with pan-human coronavirus antiviral activity. Our results show that both GC376 and NMV are capable of strongly binding to SARS-CoV-2 Mpro and altering the monomer-dimer equilibrium by stabilizing the dimeric state. This behavior is proposed to be related to a structured hydrogen-bond network established at the Mpro active site, where hydrogen bonds between Ser1' and Glu166/Phe140 are formed in addition to those achieved by the latter residues with GC376 or NMV.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Cisteína Endopeptidases/metabolismo , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Antivirais/farmacologia , Antivirais/química , Simulação de Acoplamento Molecular
17.
Child Neuropsychol ; 29(2): 276-298, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35668031

RESUMO

This study examined the executive function (EF) of children with a history of arterial ischemic stroke (AIS) and preserved intellectual abilities, with reference to age at stroke onset, lesion characteristics, language, and motor functioning. In addition, the associations between EF and emotional and behavioral functioning were investigated. A battery of standardized neuropsychological tests was administered to children with previous AIS aged 7-12 in order to assess EF, including inhibition, working memory, cognitive flexibility, and attention. Parents rated questionnaires regarding real-life emotional and behavioral functioning. Finally, clinical and neuroradiological data were also gathered. Thirty patients were enrolled. Eight children fall in the lower end of the normative range or below in more than half of the EF measures, with working memory, inhibition and cognitive flexibility equally impaired, and attention relatively better preserved. Larger lesion size and language deficits were significantly associated with higher EF impairment. Emotional and behavioral functioning was lower in children with weaker EF. Children with a history of AIS, even those with preserved intellectual functioning, have a high risk of showing poor EF, mostly regardless of clinical features or functional impairment. EF difficulties are in turn associated with emotional and behavioral problems. Therefore, a standardized evaluation of EF in this population is mandatory as part of the follow-up, in order to ensure an early intervention and prevent related difficulties.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Criança , Função Executiva/fisiologia , AVC Isquêmico/complicações , Testes Neuropsicológicos , Atenção/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia
18.
Disabil Rehabil ; 45(25): 4175-4189, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36384380

RESUMO

PURPOSE: To provide an overview of the effects of pediatric stroke on emotional and social functioning in childhood. METHODS: A literature review was completed in accordance with the Preferred Reporting Items for Systematic Reviews. A systematic search of studies on internalizing problems and social functioning after pediatric stroke in PsycInfo, PsycArticles, and PubMed databases was conducted from inception to November 2021. A total of 583 studies were identified, and 32 met the inclusion criteria. RESULTS: The review suggests that children after stroke are at risk of developing internalizing problems and a wide range of social difficulties. Internalizing problems are often associated with environmental factors such as family functioning and parents' mental health. In addition, a higher risk of developing psychosocial problems is associated with lower cognitive functioning and severe neurological impairment. CONCLUSIONS: The assessment of psychological well-being and social functioning after pediatric stroke is helpful to provide adequate support to children and their families. Future studies are needed to better investigate these domains and to develop adequate methodologies for specific interventions.Implication for rehabilitationThis paper reviews research concerning emotional and social functioning following pediatric stroke in order to provide helpful information to clinicians and families and to improve rehabilitation pathways.Emotional and social functioning should be addressed during post-stroke evaluation and follow-up, even when physical and cognitive recovery is progressing well.Care in pediatric stroke should include volitional treatment and address emotional and social issues.


Assuntos
Interação Social , Acidente Vascular Cerebral , Criança , Humanos , Ajustamento Social , Emoções
19.
Polymers (Basel) ; 14(19)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36236016

RESUMO

In this study, we unravel the atomic structure of a covalent resin near boundaries such as surfaces and composite constituents. For this, a molecular simulation analysis of epoxy resin hardening under various boundary conditions was performed. On the atomic level of detail, molecular dynamics simulations were employed to study crosslinking reactions and self-organization of the polymer network within nm scale slab models. The resulting structures were then coarsened into a graph theoretical description for connectivity analysis of the nodes and combined with characterization of the node-to-node vector orientation. On this basis, we show that the local bonding of epoxy resins near interfaces tends to avoid under-coordinated linker sites. For both epoxy-vacuum surface models and epoxy-silica/epoxy cellulose interfaces, we find almost fully cured polymer networks. These feature a local increase in network linking lateral to the surface/interface, rather than the dangling of unreacted epoxy groups. Consequently, interface tension is low (as compared to the work of separating bulk epoxy), and the reactivity of the resin surface appears negligible.

20.
Biomolecules ; 12(10)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36291641

RESUMO

The translation factor IF5A is a highly conserved protein playing a well-recognized and well-characterized role in protein synthesis; nevertheless, some of its features as well as its abundance in the cell suggest that it may perform additional functions related to RNA metabolism. Here, we have undertaken a structural and functional characterization of aIF5A from the crenarchaeal Sulfolobus solfataricus model organism. We confirm the association of aIF5A with several RNA molecules in vivo and demonstrate that the protein is endowed with a ribonuclease activity which is specific for long and structured RNA. By means of biochemical and structural approaches we show that aIF5A can exist in both monomeric and dimeric conformations and the monomer formation is favored by the association with RNA. Finally, modelling of the three-dimensional structure of S. solfataricus aIF5A shows an extended positively charged surface which may explain its strong tendency to associate to RNA in vivo.


Assuntos
Sulfolobus solfataricus , Sulfolobus solfataricus/genética , Sulfolobus solfataricus/metabolismo , Biossíntese de Proteínas , RNA/metabolismo , Ribonucleases/genética
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