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1.
Rapid Commun Mass Spectrom ; 38(1): e9650, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38073197

RESUMO

The analysis of the nitrogen (N) isotopic composition of organic matter bound to fossil biomineral structures (BB-δ15 N) using the oxidation-denitrifier (O-D) method provides a novel tool to study past changes in N cycling processes. METHODS: We report a set of methodological improvements to the O-D method, including (a) a method for sealing the reaction vials in which the oxidation of organic N to NO3 - takes place, (b) a recipe for bypassing the pH adjustment step before the bacterial conversion of NO3 - to N2 O, and (c) a method for storing recrystallized dipotassium peroxodisulfate (K2 S2 O8 ) under Ar atmosphere. RESULTS: The new sealing method eliminates the occasional contamination and vial breakage that occurred previously while increasing sample throughput. The protocol for bypassing pH adjustment does not affect BB-δ15 N, and it significantly reduces the processing time. Storage of K2 S2 O8 reagent under Ar atmosphere produces stable oxidation blanks over more than 3.5 years. We report analytical blanks, accuracy, and precision for this methodology from eight users over the course of ~3.5 years of analyses at the Max Planck Institute for Chemistry. Our method produces analytical blanks characterized by low N content (0.30 ± 0.13 nmol N, 1σ, n = 195) and stable δ15 N (-2.20 ± 3.13‰, n = 195). The analysis of reference amino acid standards USGS 40 and USGS 65 indicates an overall accuracy of -0.23 ± 0.35‰ (1σ, n = 891). The analysis of in-house fossil standards gives similar analytical precision (1σ) across a range of BB-δ15 N values and biominerals: zooxanthellate coral standard PO-1 (6.08 ± 0.21‰, n = 267), azooxanthellate coral standard LO-1 (10.20 ± 0.28‰, n = 258), foraminifera standard MF-1 (5.92 ± 0.28‰, n = 243), and tooth enamel AG-Lox (4.06 ± 0.49‰, n = 78). CONCLUSIONS: The methodological improvements significantly increase sample throughput without compromising analytical precision or accuracy down to 1 nmol of N.

2.
Mar Pollut Bull ; 197: 115757, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37988964

RESUMO

Most anthropogenic nitrogen (N) reaches coastal waters via rivers carrying increasing loads of sewage, fertilizer, and sediments. To understand anthropogenic N impacts, we need to understand historical N-dynamics before human influence. Stable isotope ratios of N preserved in carbonates are one way to create temporal N records. However, records that span periods of human occupation are scarce, limiting our ability to contextualize modern N dynamics. Here, we produce a fossil-bound N-record using coral subfossils, spanning 6700 years in China's Greater Bay Area (GBA). We found that during the mid-to-late Holocene, the GBA's coastal N was dominated by fluvial sources. The weakening of the Asia monsoon throughout the late-Holocene decreased river outflow, leading to a relative increase of marine nitrate. This source shift from riverine-to-ocean dominance was overprinted by anthropogenic N. During the late 1980s to early 1990s, human development and associated effluent inundated the coastal system, contributing to the decline of coral communities.


Assuntos
Antozoários , Nitrogênio , Animais , Humanos , Nitrogênio/análise , Monitoramento Ambiental , Isótopos , Carbonatos , Rios , China , Isótopos de Nitrogênio/análise
3.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37373396

RESUMO

The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50-120 cells/mm2 in all conditions), scarring (5-10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10-20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery.


Assuntos
Organofosfonatos , Traumatismos da Medula Espinal , Ratos , Animais , Hidrogéis/química , Organofosfonatos/metabolismo , Cicatriz/patologia , Ratos Sprague-Dawley , Regeneração Nervosa , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Axônios/patologia , Alicerces Teciduais/química
4.
Commun Biol ; 6(1): 373, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029186

RESUMO

Nitrogen isotopes are widely used to study the trophic position of animals in modern food webs; however, their application in the fossil record is severely limited by degradation of organic material during fossilization. In this study, we show that the nitrogen isotope composition of organic matter preserved in mammalian tooth enamel (δ15Nenamel) records diet and trophic position. The δ15Nenamel of modern African mammals shows a 3.7‰ increase between herbivores and carnivores as expected from trophic enrichment, and there is a strong positive correlation between δ15Nenamel and δ15Nbone-collagen values from the same individuals. Additionally, δ15Nenamel values of Late Pleistocene fossil teeth preserve diet and trophic level information, despite complete diagenetic loss of collagen in the same specimens. We demonstrate that δ15Nenamel represents a powerful geochemical proxy for diet that is applicable to fossils and can help delineate major dietary transitions in ancient vertebrate lineages.


Assuntos
Cadeia Alimentar , Mamíferos , Animais , Isótopos de Nitrogênio/análise , Isótopos de Carbono/análise , Colágeno/química , Esmalte Dentário/química , Esmalte Dentário/metabolismo
5.
Ann Clin Transl Neurol ; 10(4): 632-643, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36861178

RESUMO

OBJECTIVES: Mutations in VCP, HNRNPA2B1, HNRNPA1, and SQSTM1, encoding RNA-binding proteins or proteins in quality-control pathways, cause multisystem proteinopathies (MSP). They share pathological findings of protein aggregation and clinical combinations of inclusion body myopathy (IBM), neurodegeneration [motor neuron disorder (MND)/frontotemporal dementia (FTD)], and Paget disease of bone (PDB). Subsequently, additional genes were linked to similar but not full clinical-pathological spectrum (MSP-like disorders). We aimed to define the phenotypic-genotypic spectrum of MSP and MSP-like disorders at our institution, including long-term follow-up features. METHODS: We searched the Mayo Clinic database (January 2010-June 2022) to identify patients with mutations in MSP and MSP-like disorders causative genes. Medical records were reviewed. RESULTS: Thirty-one individuals (27 families) had pathogenic mutations in: VCP (n = 17), SQSTM1 + TIA1 (n = 5), TIA1 (n = 5), MATR3, HNRNPA1, HSPB8, and TFG (n = 1, each). Myopathy occurred in all but 2 VCP-MSP patients with disease onset at age 52 (median). Weakness pattern was limb-girdle in 12/15 VCP-MSP and HSPB8 patient, and distal-predominant in other MSP and MSP-like disorders. Twenty/24 muscle biopsies showed rimmed vacuolar myopathy. MND and FTD occurred in 5 (4 VCP, 1 TFG) and 4 (3 VCP, 1 SQSTM1 + TIA1) patients, respectively. PDB manifested in 4 VCP-MSP. Diastolic dysfunction occurred in 2 VCP-MSP. After 11.5 years (median) from symptom onset, 15 patients ambulated without gait-aids; loss of ambulation (n = 5) and death (n = 3) were recorded only in VCP-MSP. INTERPRETATION: VCP-MSP was the most common disorder; rimmed vacuolar myopathy was the most frequent manifestation; distal-predominant weakness occurred frequently in non-VCP-MSP; and cardiac involvement was observed only in VCP-MSP.


Assuntos
Demência Frontotemporal , Doenças Musculares , Humanos , Pessoa de Meia-Idade , Demência Frontotemporal/genética , Proteína com Valosina/genética , Proteína Sequestossoma-1/genética , Doenças Musculares/genética , Proteínas de Ligação a RNA , Proteínas Associadas à Matriz Nuclear
6.
Therap Adv Gastroenterol ; 16: 17562848231156285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910163

RESUMO

Background: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity. Objectives: We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD. Design: This is a multicentre cohort study conducted in five European FMT centres. Methods: Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death. Results: In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years). Conclusion: FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.

8.
Front Mol Neurosci ; 15: 1004518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36176960

RESUMO

Fast three-dimensional imaging of freely-swimming zebrafish is essential to understand the link between neuronal activity and behavioral changes during epileptic seizures. Studying the complex spatiotemporal patterns of neuronal activity at the whole-brain or -body level typically requires physical restraint, thus hindering the observation of unperturbed behavior. Here we report on real-time volumetric optoacoustic imaging of aberrant circular swimming activity and calcium transients in freely behaving zebrafish larvae, continuously covering their motion across an entire three-dimensional region. The high spatiotemporal resolution of the technique enables capturing ictal-like epileptic seizure events and quantifying their propagation speed, independently validated with simultaneous widefield fluorescence recordings. The work sets the stage for discerning functional interconnections between zebrafish behavior and neuronal activity for studying fundamental mechanisms of epilepsy and in vivo validation of treatment strategies.

9.
Muscle Nerve ; 66(4): 479-486, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35894586

RESUMO

INTRODUCTION/AIMS: Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure-palsies (HNPP) and Charcot-Marie-Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. METHODS: Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression. RESULTS: CTS occurred in 53.3% of HNPP and 11.5% of CMT1A, while CuTS was present in 43.3% of HNPP and 5.8% of CMT1A patients. CTS decompression occurred in 10-HNPP and 5-CMT1A patients, and CuTS decompression with/without transposition was performed in 5-HNPP and 1-CMT1A patients. In HNPP, electrodiagnostic studies identified median neuropathy at the wrist in 9/10 patients and ultrasound showed focal enlargements at the carpal and cubital tunnels. In CMT1A, median and ulnar sensory responses were all absent, and the nerves were diffusely enlarged. After CTS surgery, pain, sensory loss, and strength improved in 4/5 CMT1A, and 6/10 HNPP patients. Of clinical, electrophysiologic and ultrasound findings, only activity-provoked features significantly correlated with CTS surgical benefit in HNPP patients (odds ratio = 117.0:95% confidence interval, 1.94 > 999.99, p = 0.01). One CMT1A and one HNPP patient improved with CuTS surgery while 2 HNPP patients worsened. DISCUSSION: CTS symptom improvement post-surgery can be seen in CMT1A and (less frequent) in HNPP patients. CuTS surgery commonly worsened course in HNPP. Activity-provoked symptoms in HNPP best informed benefits from CTS surgery.


Assuntos
Doença de Charcot-Marie-Tooth , Neuropatia Hereditária Motora e Sensorial , Artrogripose , Doença de Charcot-Marie-Tooth/genética , Descompressão , Neuropatia Hereditária Motora e Sensorial/genética , Neuropatia Hereditária Motora e Sensorial/cirurgia , Humanos , Qualidade de Vida
10.
Artigo em Inglês | MEDLINE | ID: mdl-35618531

RESUMO

OBJECTIVE: Functional mitral regurgitation (FMR) is a cardiac pathology that causes the mitral valve to malfunction, leading to mitral regurgitation (MR). The optimal strategy for FMR remains unclear, and FMR outcomes are poor. All etiologies of FMR might not be the same, and subdividing patients with FMR caused by atrial (AFMR) versus ventricular FMR pathology might be important. Herein, we present outcomes of patients with AFMR to define this "new" population. METHODS: Data of patients who underwent mitral valve repair for MR from 2000 to 2020 were reviewed. Patients with degenerative/myxomatous disease, ejection fraction <50% (ventricular FMR), and miscellaneous etiologies including endocarditis and rheumatic disease were excluded to isolate a population of "pure" AFMR patients. Descriptive characteristics and outcomes data were analyzed. RESULTS: Among 123 total AFMR patients, mean preoperative left atrial dimensions were enlarged to 4.9 (95% CI, 4.7-5.0) cm, whereas mean preoperative left ventricular diastolic dimensions remained near normal at 5.0 (95% CI, 4.9-5.2) cm. Preoperative atrial fibrillation was noted in 61% (74/123). Echocardiogram was performed in 58% (71/123) of patients at a median of 569 (interquartile range, 75-1782) days after surgery. Of those, 72% (51/71) had trivial or no MR, 22% (16/71) mild, and only 6% (4/71) moderate or greater MR. Only 1.6% (2/123) required redo mitral valve reoperation. Estimated 5-year survival was 74%. CONCLUSIONS: Patients with AFMR do well after mitral valve repair using an annuloplasty ring, with low rates of reoperation, mortality, and recurrence of MR. Mitral annuloplasty should be considered the surgical therapy of choice for AFMR.

11.
Neuroscientist ; 28(2): 163-179, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33089762

RESUMO

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a translesional spinal network after SCI. We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI. We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.


Assuntos
Traumatismos da Medula Espinal , Medula Espinal , Humanos , Recuperação de Função Fisiológica
12.
Leukemia ; 36(3): 637-647, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34711926

RESUMO

Aberrant RHO guanine nucleotide exchange factor (RhoGEF) activation is chief mechanism driving abnormal activation of their GTPase targets in transformation and tumorigenesis. Consequently, a small-molecule inhibitor of RhoGEF can make an anti-cancer drug. We used cellular, mouse, and humanized models of RAC-dependent BCR-ABL1-driven and Ph-like acute lymphoblastic leukemia to identify VAV3, a tyrosine phosphorylation-dependent RacGEF, as the target of the small molecule IODVA1. We show that through binding to VAV3, IODVA1 inhibits RAC activation and signaling and increases pro-apoptotic activity in BCR-ABL1-transformed cells. Consistent with this mechanism of action, cellular and animal models of BCR-ABL1-induced leukemia in Vav3-null background do not respond to IODVA1. By durably decreasing in vivo RAC signaling, IODVA1 eradicates leukemic propagating activity of TKI-resistant BCR-ABL1(T315I) B-ALL cells after treatment withdrawal. Importantly, IODVA1 suppresses the leukemic burden in the treatment refractory pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models better than standard-of-care dasatinib or ponatinib and provides a more durable response after treatment withdrawal. Pediatric leukemia samples with diverse genetic lesions show high sensitivity to IODVA1 ex vivo and this sensitivity is VAV3 dependent. IODVA1 thus spearheads a novel class of drugs that inhibits a RacGEF and holds promise as an anti-tumor therapy.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-vav/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos SCID , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-vav/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Células Tumorais Cultivadas
13.
Glia ; 70(1): 196-214, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34716961

RESUMO

Astroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, and SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Hence, an impairment in EAAT2 function could lead to an imbalanced brain network excitability. Here, we investigated the functional alterations of neuronal and astroglial networks associated with the loss of function in the astroglia predominant eaat2a gene in zebrafish. We observed that eaat2a-/- mutant zebrafish larvae display recurrent spontaneous and light-induced seizures in neurons and astroglia, which coincide with an abrupt increase in extracellular glutamate levels. In stark contrast to this hyperexcitability, basal neuronal and astroglial activity was surprisingly reduced in eaat2a-/- mutant animals, which manifested in decreased overall locomotion. Our results reveal an essential and mechanistic contribution of EAAT2a in balancing brain excitability, and its direct link to epileptic seizures.


Assuntos
Epilepsia , Peixe-Zebra , Animais , Astrócitos/metabolismo , Epilepsia/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/metabolismo , Ácido Glutâmico/metabolismo , Neurônios/metabolismo , Convulsões/genética , Convulsões/metabolismo , Peixe-Zebra/metabolismo
14.
Minerva Urol Nephrol ; 74(4): 467-474, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33781016

RESUMO

BACKGROUND: Green Light laser enucleation of the prostate (GreenLEP) is an endoscopic treatment to treat bladder outlet obstruction in men with large prostate (>100 cc). Herein, we describe our GreenLEP series and describe its safety and efficacy. METHODS: Between February 2014 and April 2019, 120 patients from a single center underwent en-bloc GreenLEP with early apical release. All procedures were performed with the AMS XPS laser generator (set: 120 W for vaporization and 20 W for coagulation). Morcellation was carried out with the Wolf Piranha morcellator. Data concerning the pre-, intra- and postoperative outcomes were prospectively collected. The follow-up data at 6, 12 months and at the last control were collected. RESULTS: The median age was 66.0 (IQR: 61.0-71.0) years; 37.5% of the patients were under antiplatelet/anticoagulant therapy, 15.0% had indwelling catheter history. The median prostate volume and the baseline PSA value were 98.5 mL (IQR 83.0-130.0) and 4.2 ng/mL (IQR: 3.2-6.8), respectively. The median operative and lasing time were 65.0 (IQR: 51.0-83.5) and 6.0 (IQR: 6.0-10.0) minutes, respectively. In the postoperative period 1 patient was transfused. The median follow-up was 18.0 (IQR: 12.0-39.5) months. All patients had significant improvement in terms of improvement of uroflowmetry (median from 9 mL/sec [IQR 7.8, 11.0] to 20.0 [IQR 18.0, 22.0], P<0.001) and symptoms control (IPSS median score from 26.0 mL/sec [IQR 22.0, 28.0] to 7.0 [IQR 6.0, 8.0], P<0.001]) over time. After 12 months 1 patient complained of stress incontinence (1 pad/day) and 1 of "de novo" wet urgency. CONCLUSIONS: En-bloc GreenLEP with early apical release is a safe and effective procedure even for large volume prostates. It allows us to limit the use of laser energy and shorten the operating times with stable and satisfactory long-term outcomes.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Próstata/diagnóstico por imagem , Próstata/cirurgia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento
15.
AJNR Am J Neuroradiol ; 43(1): 151-156, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34887247

RESUMO

BACKGROUND AND PURPOSE: A new brain tumor entity occurring in early childhood characterized by a somatic BCL6 corepressor gene internal tandem duplication was recently described. The aim of this study was to describe the radiologic pattern of these tumors and correlate this pattern with histopathologic findings. MATERIALS AND METHODS: This retrospective, noninterventional study included 10 children diagnosed with a CNS tumor, either by ribonucleic acid-sequencing analysis or deoxyribonucleic acid methylation analysis. Clinical, radiologic, and histopathologic data were collected. A neuropathologist reviewed 9 tumor samples. Preoperative images were analyzed in consensus by 7 pediatric radiologists. RESULTS: All tumors were relatively large (range, 4.7-9.2 cm) intra-axial peripheral masses with well-defined borders and no peritumoral edema. All tumors showed mild and heterogeneous enhancement and marked restriction on DWI of the solid portions. Perfusion imaging showed a relatively lower CBF in the tumor than in the adjacent normal parenchyma. Nine of 10 tumors showed areas of necrosis, with the presence of hemorrhage in 8/10 and calcifications in 4/7. Large intratumoral macroscopic veins were observed in 9/10 patients. No intracranial or spinal leptomeningeal dissemination was noted at diagnosis. CONCLUSIONS: CNS tumors with a BCL6 corepressor gene internal tandem duplication present as large intra-axial peripheral masses with well-defined borders, no edema, restricted diffusion, weak contrast enhancement, frequent central necrosis, hemorrhage and calcifications, intratumoral veins, and no leptomeningeal dissemination at the time of diagnosis. Knowledge of these imaging characteristics may aid in histologic, genomic, and molecular profiling of brain tumors in young children.


Assuntos
Neoplasias Encefálicas , Neoplasias Neuroepiteliomatosas , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Estudos Retrospectivos
16.
NPJ Regen Med ; 6(1): 66, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671050

RESUMO

Here, we report the effect of newly regenerated axons via scaffolds on reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation (EES). Motor recovery was evaluated for 7 weeks after spinal transection and following implantation with scaffolds seeded with neurotrophin producing Schwann cell and with rapamycin microspheres. Combined treatment with scaffolds and EES-enabled stepping led to functional improvement compared to groups with scaffold or EES, although, the number of axons across scaffolds was not different between groups. Re-transection through the scaffold at week 6 reduced EES-enabled stepping, still demonstrating better performance compared to the other groups. Greater synaptic reorganization in the presence of regenerated axons was found in group with combined therapy. These findings suggest that newly regenerated axons through cell-containing scaffolds with EES-enabled motor training reorganize the sub-lesional circuitry improving motor recovery, demonstrating that neuroregenerative and neuromodulatory therapies cumulatively enhancing motor function after complete SCI.

17.
Appl Ergon ; 97: 103505, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34175677

RESUMO

This study aimed to characterize the effects of walking with backpack load on upper limb function. Fifteen males participated in 3 conditions: no load, 40% body weight loaded backpack (BP) and loaded backpack with simulated rifle (BRC). Pinch strength, grip strength, sensory threshold, blood flow volume, and a manual dexterity test were assessed before and after a 45-min walking trial. Pinch strength in the BP condition was significantly different than the control (p < 0.05). Grooved pegboard times were faster after a seated recovery (p = 0.026) than immediately after walking with load. Blood flow was significantly decreased to <53% of baseline (p ≤ 0.001) in BP and BRC immediately after donning the backpack. No significant changes in grip strength or sensory threshold were measured among conditions or time points. In conclusion, pinch strength, manual dexterity and blood flow were affected by backpack carriage, but other upper limb measures remained unaffected.


Assuntos
Hemodinâmica , Caminhada , Fenômenos Biomecânicos , Humanos , Masculino , Força de Pinça , Extremidade Superior , Suporte de Carga
18.
Sci Adv ; 7(23)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34078610

RESUMO

Recently, we published a novel method used to assess the trophic niches of different coral species and demonstrated that their nutrition varied considerably, with some species highly dependent on their photosynthetic algal symbionts and others able to feed on plankton to meet energetic requirements. Adjustments to the use of this tool are necessary when it is applied to other scientific questions and symbiotic organisms. We respond to a comment highlighting a risk of bias in the methods, discuss suggested adjustments, and propose further refinements to improve method robustness.

19.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1389772

RESUMO

Resumen Introducción: La otitis media crónica simple (OMC) es una patología común en nuestra población y hasta la fecha no queda bien claro cuál técnica y material de injerto da mejores resultados. Objetivo: Determinar si existen diferencias en los resultados anatómicos y funcionales al utilizar fascia de músculo temporal (FMT) versus injerto de cartílago de trago (CT) en los pacientes con OMC en que se les realizó miringoplastía en el Hospital Barros Luco Trudeau. Material y Método: Estudio de cohorte no concurrente de datos obtenidos de la revisión de fichas clínicas. Resultados: De 227 fichas, 154 cumplieron criterios de inclusión. En 102 pacientes (66%) se utilizó FMT y en 52 pacientes (34%) CT. Con FMT 38 presentaron reperforación (37%) y 41 presentaron un éxito funcional (40%). Con CT 18 presentaron reperforación (35%) y 22 presentaron un éxito funcional (42%). 38 pacientes presentaban antecedente de tabaquismo activo y de ellos 53% presentaron reperforación, mientras que de los sin antecedentes de tabaquismo solo un 31%, siendo esta diferencia estadísticamente significativa (p < 0,05). Conclusión: No se obtuvieron diferencias estadísticamente significativas entre los resultados anatómicos y funcionales comparando el uso de injerto FMT y CT para el tratamiento quirúrgico de la OMC simple con miringoplastía.


Abstract Introduction: Simple chronic otitis media (COM) is a common pathology in our population, and it is currently unclear, which grafts technique and material gives the best results. Aim: To determine if there are differences in the anatomical and functional results, when using temporal muscle fascia (FMT) or tragus cartilage graft (CT) in patients with COM who underwent myringoplasty at the Barros Luco Trudeau Hospital. Material and Method: Retrospective analytical cohort study of data obtained from clinical records. Results: Of 227 medical records, 154 met inclusion criteria. FMT was used in 102 patients (66%) and CT in 52 patients (34%). With FMT, 38 had reperforation (37%) and 41 had functional success (40%). With CT 18 had reperforation (35%) and 22 had functional success (42%). 38 patients had a history of active smoking and 53% of them presented reperforation, while of those without a history of smoking only 31%, this difference being statistically significant (p < 0,05). Conclusion: No statistically significant differences were obtained when analyzing the anatomical and functional results comparing the use of FMT and CT graft, for the simple surgical treatment of COM with myringoplasty.

20.
Biomedicines ; 9(5)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925613

RESUMO

Spinal cord injury (SCI) results in cell death, demyelination, and axonal loss. The spinal cord has a limited ability to regenerate, and current clinical therapies for SCI are not effective in helping promote neurologic recovery. We have developed a novel scaffold biomaterial that is fabricated from the biodegradable hydrogel oligo(poly(ethylene glycol)fumarate) (OPF). We have previously shown that positively charged OPF scaffolds (OPF+) in an open spaced, multichannel design can be loaded with Schwann cells to support axonal generation and functional recovery following SCI. We have now developed a hybrid OPF+ biomaterial that increases the surface area available for cell attachment and that contains an aligned microarchitecture and extracellular matrix (ECM) proteins to better support axonal regeneration. OPF+ was fabricated as 0.08 mm thick sheets containing 100 µm high polymer ridges that self-assemble into a spiral shape when hydrated. Laminin, fibronectin, or collagen I coating promoted neuron attachment and axonal outgrowth on the scaffold surface. In addition, the ridges aligned axons in a longitudinal bipolar orientation. Decreasing the space between the ridges increased the number of cells and neurites aligned in the direction of the ridge. Schwann cells seeded on laminin coated OPF+ sheets aligned along the ridges over a 6-day period and could myelinate dorsal root ganglion neurons over 4 weeks. This novel scaffold design, with closer spaced ridges and Schwann cells, is a novel biomaterial construct to promote regeneration after SCI.

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